Table of Contents
Overview
Definition and Scope
Cell engineering is a multifaceted discipline that encompasses the manipulation of cells to enhance their production capabilities or to create novel therapeutic solutions. One significant aspect of cell engineering involves altering natural cell production processes to achieve improved yields or reduced production times. This can be accomplished through methods such as boosting or repressing specific genes that are integral to the metabolism of desired products, including proteins, antibodies, or enzymes.[1.1] The field is closely associated with biotechnology, employing recombinant DNA techniques to induce cells to synthesize products that can be utilized in various medical applications. For instance, Escherichia coli has been genetically modified to express human growth hormone, which is used in the treatment of conditions like pituitary dwarfism. Additionally, advancements in cell engineering have facilitated the production of antigens for vaccine development.[1.1] The integration of stem cell and tissue engineering concepts has further expanded the scope of cell engineering, particularly since the 1990s. This integration has led to innovative solutions for healthcare challenges related to cellular deficiencies and physical trauma, with the transplantation of stem cells dating back to 1968.[2.1] Moreover, a new era of biological engineering is emerging, wherein living cells are utilized as building blocks to tackle therapeutic challenges. This approach diverges from traditional molecular engineering by focusing on the reprogramming of cellular decision-making and communication rather than merely optimizing individual genes and proteins.[3.1]Applications in Biomedical Research
Recent advancements in cell engineering have significantly influenced biomedical research, particularly through the application of stem cell technologies and tissue engineering strategies. Stem cell therapy has emerged as a promising approach for tissue regeneration; however, its clinical application is often limited by the poor survival and differentiation potentials of transplanted cells. To address these challenges, researchers are developing multi-layered 3D scaffolds that facilitate the construction of engineered tissues using stem cells, thereby enhancing therapeutic efficacy.[5.1] Innovative techniques such as magnetic-activated cell sorting (MACS) have been employed for the isolation of stem cells from mixed cell populations. This method utilizes magnetic nanoparticles to label specific stem cell types, allowing for their efficient separation and subsequent application in therapeutic contexts.[7.1] Furthermore, the differentiation of human induced pluripotent stem cells (hiPSCs) into cardiomyocytes has opened new avenues for creating in vitro cardiac models, which are invaluable for studying heart diseases and testing potential treatments.[8.1] The viscosity of the surrounding fluid has also been shown to impact stem cell development, suggesting that the physical properties of the microenvironment can be manipulated to influence cell behavior and enhance regenerative outcomes.[9.1] Additionally, the integration of microfluidics and 3D bioprinting technologies has enabled the creation of biomimetic physiological tissue structures, which are crucial for drug discovery and personalized medicine applications.[10.1] As the field of personalized medicine evolves, stem cells are poised to play a transformative role by enabling tailored therapies and improving drug development processes. Advancements in gene editing technologies, such as CRISPR, offer the potential to correct genetic defects in patient-derived stem cells, thereby enhancing the efficacy of personalized treatments.[11.1] The intersection of stem cells and personalized medicine not only holds promise for developing targeted therapies but also for understanding disease mechanisms and improving regenerative treatments.[13.1]History
Early Developments
The early developments in cell engineering can be traced back to significant advancements in cell biology and technology. The invention of the compound microscope in 1595 marked a pivotal moment, enabling scientists to visualize cells for the first time. This was further advanced by Robert Hooke's observation of cork cells in 1655 and Anton van Leeuwenhoek's examination of live cells in 1674, which laid the groundwork for understanding cellular structures and functions.[48.1] The field of genetic engineering emerged as a distinct discipline in the 1970s, focusing on modifying an organism's genetic material through the addition or deletion of genes. This period saw the development of transfection methods, greatly facilitated by advances in electron microscopy, which allowed for more precise manipulation of cellular components.[47.1] By the late twentieth century and early twenty-first century, the advent of 3-D cell culture technology opened new avenues for tissue engineering and regenerative medicine. This innovation allowed for more complex interactions between cells, mimicking natural tissue environments and enhancing the potential for therapeutic applications.[46.1] Moreover, the clinical validation of engineered immune cells designed to target cancer exemplifies the practical applications of cell engineering. This toolkit for rewiring cell connectivity is now being adapted for various diseases and for programming the self-organization of tissues and organs, showcasing the evolution of cell engineering from foundational discoveries to cutting-edge therapies.[45.1]Evolution of Techniques
The evolution of techniques in cell engineering has been characterized by transformative advancements and persistent challenges, particularly in cancer treatment. Engineered immune cell therapies, such as chimeric antigen receptor (CAR) T cell therapy, have revolutionized the treatment of hematological malignancies. However, adapting these therapies to solid tumors remains challenging due to T cell dysfunction and the complex nature of the solid tumor microenvironment (TME), which reduces CAR T cell efficacy.[55.1] Recent innovations, such as engineered T cell receptor (TCR) therapies, have expanded the potential for targeting cancer cells by recognizing intracellular antigens, as demonstrated by the first patient treated with Tecelra at Stanford Cancer Institute in January 2025.[56.1] These developments reflect a broader trend in cancer immunotherapy, which has become integral to cancer treatment by optimizing immune responses and addressing patient-specific immune suppressive mechanisms.[57.1] Advancements in cell engineering techniques, including base editing and dual antigen targeting, have enhanced the safety and efficacy of therapies for various cancer types, particularly hematological malignancies.[58.1] Despite these advancements, bioprinting technology faces significant challenges, such as the standardization of process parameters and the sensitivity of outcomes to environmental variations.[63.1] While bioprinting holds promise for creating complex tissue structures for medical research and organ transplantation, technical, ethical, and regulatory challenges complicate the path to fully functional bioprinted organs.[64.1] As the field advances, the ethical implications of genetic engineering and gene therapy are increasingly scrutinized. The discourse on the morality of genetic manipulation underscores the need for responsible advancements that balance potential benefits with ethical considerations.[61.1] Ongoing dialogue among researchers, ethicists, and regulatory bodies is crucial to navigating the complexities of gene editing, particularly concerning therapeutic applications versus enhancements.[62.1]In this section:
Recent Advancements
Genetic Engineering Techniques
Recent advancements in genetic engineering techniques have significantly transformed the landscape of biomedical research and therapeutic applications. One of the most notable innovations is the CRISPR/Cas9 gene-editing technology, which has emerged as a powerful tool for precise genome modification. The mechanism of CRISPR/Cas9 involves the use of an RNA guide molecule that targets specific DNA sequences, allowing the Cas9 enzyme to induce precise DNA cleavage, thereby enabling the correction of deleterious mutations or the disruption of disease-causing genes with high efficiency.[114.1] The first clinical application of CRISPR/Cas9 gene editing occurred in 2016, when a clinical trial successfully delivered CRISPR gene-edited immune cells to a patient with advanced lung cancer.[100.1] This development highlighted the significant potential of CRISPR technology in cancer treatment; however, concerns regarding its long-term safety and the possibility of off-target effects remain critical issues that need to be addressed.[101.1] Despite these challenges, CRISPR-Cas9 technology offers revolutionary strategies for cancer therapy by enabling precise genome editing to target oncogenes, thereby providing novel approaches for intervention in malignancies.[102.1] Over the past decade, CRISPR has transformed biomedical research, offering new insights into cancer genetics and therapeutic vulnerabilities, which may enhance diagnosis and treatment strategies.[104.1] Recent advancements in CRISPR/Cas9 technology have significantly impacted gene therapy for genetic disorders, particularly through clinical trials targeting β-thalassemia and severe sickle cell disease. To date, three clinical trials have been initiated by CRISPR Therapeutics in 2018 and Allife Medical Science and Technology Co., Ltd in 2019, which involve the transfusion of CRISPR/Cas9 edited CD34+ human hematopoietic stem cells (HSCs).[113.1] While the approval of Casgevy for sickle cell disease in 2023 represents a notable development in the field, challenges remain in the effective delivery of the CRISPR system to diseased cells in vivo. Current research is focusing on developing nonviral vectors with target recognition functions to enhance delivery efficacy, addressing the ongoing challenges associated with CRISPR/Cas9 technology in disease treatment.[114.1] Moreover, advancements in CRISPR technology have led to the development of switchable Cas9 variants, which allow for controlled gene editing in response to external stimuli. This feature enhances the spatiotemporal control of gene editing, making it particularly desirable for specific therapeutic applications.[115.1] As research continues, the focus on improving delivery mechanisms for CRISPR systems to target diseased cells in vivo is expected to be a critical area of development, addressing current limitations and expanding the therapeutic potential of genetic engineering techniques.[114.1]Synthetic Biology in Cell Engineering
Recent advancements in synthetic biology have significantly enhanced the field of cell engineering, leading to innovative applications in diagnosis, treatment, and drug development. Synthetic biology provides a suite of genetic tools that enable the reprogramming and engineering of cells for improved performance and novel functionalities, which are crucial for the development of new therapeutics.[88.1] In 2023, a landmark achievement was the clinical approval of Casgevy, the first CRISPR-based gene therapy for treating sickle cell disease in the UK, marking a pivotal moment in the application of synthetic biology in medicine.[86.1] The integration of synthetic biology into cell engineering has facilitated the creation of engineered biological sensors capable of detecting disease biomarkers, such as microRNAs and cell-surface proteins. These advancements allow for more precise interactions with cellular components, including DNA editing and RNA modulation.[99.1] Furthermore, the use of precision genetic modification techniques has become more efficient and economical, enabling targeted gene editing with minimal off-target effects, which is essential for therapeutic applications.[95.1] In addition to therapeutic developments, synthetic biology has also made strides in enhancing crop traits and bioproduction through engineered modifications. Techniques such as CRISPR-Cas12 have been employed to achieve precise gene editing, accelerating the development of crops with desirable traits.[95.1] This approach not only improves agricultural productivity but also contributes to sustainable practices in biotechnology.Types Of Cell Engineering
Stem Cell Engineering
Stem cell engineering is a pivotal area of cell engineering that focuses on manipulating stem cells for therapeutic applications. This field has attracted significant attention due to its potential in regenerative medicine and its role in treating a wide range of diseases. Stem cells have the unique ability to differentiate into various cell types, making them ideal candidates for enhancing therapeutic efficacy and applicability. Research in stem cell engineering has shown promise in addressing diseases such as muscular dystrophy, heart disease, Parkinson's disease, Alzheimer's disease, spinal cord injuries, diabetes, and cancer.[134.1] The field involves identifying and isolating different stem cell types, including embryonic, induced pluripotent, and adult stem cells, which are sourced from various origins.[135.1] Recent advancements in stem cell transplantation have underscored its potential in tissue repair, particularly for bone and cartilage regeneration, neurological disorders, and hematological conditions.[135.1] Despite existing challenges, progress in stem cell engineering suggests the possibility of developing new therapies that could significantly impact these conditions.[134.1] Innovations in this field also include the development of in vitro models that mimic early mammalian development, offering insights into embryogenesis and disease modeling.[132.1] These models are essential for understanding developmental processes and testing therapeutic interventions prior to clinical application. The integration of synthetic biology into stem cell engineering has propelled the field forward by providing genetic tools for reprogramming and enhancing cell functions. These advancements are crucial for developing innovative therapeutics, facilitating applications in diagnosis, treatment, and drug development.[133.1] A notable example is the collaboration between Mekonos and bit.bio, which aims to optimize non-viral methods for cell therapies, demonstrating the potential of collaborative efforts to address challenges in stem cell engineering.[136.1] As synthetic biology evolves, it is expected to play a key role in overcoming obstacles and expanding the capabilities of regenerative medicine.Therapeutic T Cell Engineering
Therapeutic T cell engineering has emerged as a pivotal area in the development of advanced drug delivery systems, particularly in the context of targeted therapies. One of the primary challenges in this field is ensuring biocompatibility and acceptability, as the interaction between synthetic materials and human body cells differs significantly from natural biological interactions. This discrepancy can affect the effectiveness of drug delivery systems in clinical applications, particularly due to the lipophilic nature of cell membranes, which hinders the transport of hydrophilic solutes.[151.1] To address these challenges, innovative approaches such as cell membrane-cloaked nanotherapeutics have been developed. These systems integrate biomimetic features of cell membranes with multifunctional nanoparticles, creating a future-oriented platform for targeted drug delivery. By mimicking the biological properties of source cells, these engineered T cells can achieve a range of functions, including prolonged circulation time within the body, which enhances their therapeutic efficacy.[152.1] This advancement represents a significant step forward in overcoming the limitations associated with traditional drug delivery methods and improving patient outcomes in various therapeutic contexts.Challenges And Limitations
Technical Challenges
The production of high-quality recombinant proteins in mammalian cell factories faces significant technical challenges, primarily due to proteotoxic stress. This stress arises from the accumulation of improperly folded proteins, which can overwhelm the protein synthesis machinery in the endoplasmic reticulum (ER) during recombinant protein production. As a result, cells activate the Unfolded Protein Response (UPR) to cope with this stress, which can ultimately impact cell health and productivity.[181.1] In the realm of cell-based therapies, several limitations impede their broad clinical application and commercialization. These challenges encompass issues related to cell source, viability, potency, safety, and scalability.[169.1] Specifically, chimeric antigen receptor (CAR) T cell therapy, while a groundbreaking advancement in cancer treatment, faces significant obstacles. The efficacy of CAR T cells targeting solid tumors is limited by factors such as target heterogeneity, treatment-associated toxicities, and immunosuppressive elements within the tumor microenvironment (TME), which include poor T cell infiltration, metabolic stress, and T cell exhaustion.[176.1] The immunosuppressive TME presents a critical challenge for CAR T cells, characterized by the production of inhibitory cytokines like transforming growth factor β (TGF-β), which restricts CAR T cell persistence and functionality.[177.1] To address these challenges, innovative strategies are being explored, such as engineering CAR T cells to secrete pro-inflammatory soluble factors like IL-12 and IL-18, which can help reshape the TME and promote a more favorable anti-tumor response by recruiting pro-inflammatory immune cells, including M1 macrophages.[178.1] To address these challenges, innovative strategies are being explored. For instance, engineering CAR T cells to secrete pro-inflammatory factors can reshape the TME to promote a more favorable anti-tumor response.[178.1] Additionally, modifying CAR T cells to express both anti-tumor receptors and altered inhibitory receptor profiles simultaneously may enhance their efficacy against tumors.[179.1] Furthermore, advancements in antigen selection and CAR T cell modifications are being researched to improve solid tumor infiltration and overall therapeutic effectiveness.[195.1]Ethical Considerations
The evolving regulatory landscape surrounding cell engineering raises significant ethical considerations, particularly in balancing the need for innovation with patient safety and timely access to therapies. The FDA has established a new regulatory pathway for cell-based therapies in regenerative medicine, which is designed to expedite the development of therapeutic agents that are both safe and effective, and this pathway is integrated with several other tracks aimed at speeding up this process.[201.1] A primary challenge in manufacturing arises from the necessity to scale out the production of autologous cell therapy products for both multi-centric Phase III studies and the supply of marketed products to clinical sites across various regulatory jurisdictions.[201.1] This situation necessitates a debate on the role of regulators and stakeholders in making risk/benefit decisions regarding alternative business models for these therapies, including concepts such as ‘GMP in a box’ and point-of-care manufacturing.[201.1] Moreover, the European Medicines Agency (EMA) has recognized the need for regulatory requirements to adapt to the realities faced by academic centers, as evidenced by its pilot program aimed at supporting academic and non-profit organizations in translating innovative therapies.[202.1] In Japan, the establishment of the Regulatory Science Center by the PMDA in 2018 has facilitated the incorporation of innovation into the regulatory framework, utilizing clinical trial data and electronic health records to enhance safety measures.[203.1] Despite these advancements, developers of advanced therapy medicinal products (ATMPs) face stringent post-approval commitments that can hinder market performance. Additionally, non-regulatory issues such as health technology assessments, valuation, and payment policies can further complicate access to gene therapies post-approval.[204.1] As countries strive to create new regulatory frameworks to support gene therapy development, there is a pressing need for a focus on reliance to prevent delays in bringing safe and effective products to market.Future Directions
Innovations in Cell Engineering
Innovations in cell engineering are rapidly evolving, driven by advancements in various interdisciplinary fields. One significant area of focus is regenerative engineering, which integrates advanced material science, stem cell science, physics, developmental biology, and clinical translation to regenerate complex tissues and organ systems.[207.1] This convergence allows for the engineering of living tissues and organs with increasing complexity, which is essential for potential clinical applications.[208.1] A promising approach within this domain is the use of autologous stem cells, which have the potential to differentiate into nearly any cell type in the adult body, making them valuable for tissue and organ replacement.[205.1] Therapeutic cloning, also known as somatic cell nuclear transfer, may serve as an alternative source of transplantable cells, further enhancing the capabilities of tissue engineering.[205.1] Current strategies often involve "growing organs in the laboratory," where differentiated cells or stem cells are seeded onto biomaterial scaffolds that mature in vitro before implantation.[205.1] The integration of synthetic biology into cell engineering provides a bottom-up approach to understanding complex biological systems through design-build-test cycles.[211.1] This methodology is particularly relevant in embryonic development, where gene regulatory networks give rise to collective cellular behaviors that culminate in multicellular forms and functions.[211.1] Recent advancements in the differentiation of induced pluripotent stem cells (iPSCs) have highlighted the importance of specific signaling pathways that guide lineage commitment and maturation.[213.1] For instance, the sequential exposure to factors such as Activin A, Wnt3a, and keratinocyte growth factor (KGF) has been shown to enhance hepatic differentiation, resulting in hepatocyte-like cells with improved functionality.[213.1] Furthermore, the combination of modern 3D bioprinting technologies with autologous iPSC-derived grafts represents a promising tissue engineering approach, particularly for treating end-stage liver disease.[214.1] This innovative method aims to create functional and stable liver grafts using human iPS-derived cells, showcasing the potential of merging developmental biology principles with cutting-edge technologies in cell engineering.[214.1] Modern 3D bioprinting technologies represent another innovative frontier in tissue engineering. By combining iPSC-derived grafts with 3D bioprinting, researchers can create functional and stable organ constructs, such as liver grafts, which are essential for treating end-stage liver disease.[216.1] This technology allows for the precise placement of stem cells within artificial microenvironments, facilitating the development of realistic tissue models.[215.1] The use of hydrogels as bioinks for printing tissues and organs further enhances the potential for creating structures that mimic native tissue architecture and function.[216.1]In this section:
References
[1] Cell engineering - Wikipedia — Cell engineering - Wikipedia 1.5 Stem cell engineering Cell engineering One general form of cell engineering involves altering natural cell production to achieve a more desirable yield or shorter production time. A possible method for changing natural cell production includes boosting or repressing genes that are involved in the metabolism of the product. Closely tied with the field of biotechnology, this subject of cell engineering employs recombinant DNA methods to induce cells to construct a desired product such as a protein, antibody, or enzyme. Coli was transformed to express human growth hormone for use in treatment of pituitary dwarfism. Finally, much progress has been made in engineering cells to produce antigens for the purpose of creating vaccines. Stem cell engineering "Therapeutic T cell engineering". "Guidelines to cell engineering for monoclonal antibody production". Cell engineering
[2] On the Genealogy of Tissue Engineering and Regenerative Medicine — While it was not until the 1990s that the use of stem cell and tissue engineering concepts merged to produce elegant solutions to healthcare problems arising due to cellular deficiency and/or physical trauma, transplantation of stem cells had started as early as 1968. ... Vacanti C.A.The history of tissue engineering. J Cell Mol Med 10,569
[3] The emerging era of cell engineering: Harnessing the ... - Science — A new era of biological engineering is emerging in which living cells are used as building blocks to address therapeutic challenges. These efforts are distinct from traditional molecular engineering—their focus is not on optimizing individual genes and proteins as therapeutics, but rather on using molecular components as modules to reprogram how cells make decisions and communicate to
[5] Recent advances in stem cell therapeutics and tissue engineering ... — Recent advances in stem cell therapeutics and tissue engineering strategies - PMC In this review, we will discuss the progress of biomedical engineering, including scaffolds, biomaterials, and tissue engineering techniques to overcome the low therapeutic efficacy of stem cells and to treat human diseases. Although stem cell therapy provides a new paradigm in tissue regeneration, they have limitation in clinical application due to poor survival and differentiation potentials of the transplanted cells . Therefore, multi-layered 3D scaffolds are needed for construction of engineered tissues using stem cells. 3D bioprinting of stem cells Most therapies or treatments eventually aim to enhance tissue regeneration, and stem cell engineering has opened a new path to regenerative medicine. doi: 10.1016/j.stem.2013.11.014. doi: 10.1016/j.cell.2006.07.024. Biomaterials and stem cells for tissue engineering.
[7] Nanotechnology shaping stem cell therapy: Recent advances, application ... — Cell isolation is crucial in stem cell-based therapies. Magnetic cell isolation is a widely used method to feed stem cells from a blended cell population . Magnetic nanoparticles (MNPs) can label stem cells and the targeted cell types could be distinguished from a multi-cell mixture (magnetic-activated cell sorting (MACS) . This
[8] Induced pluripotent stem cell-derived cardiomyocyte in vitro models ... — Recent innovations in differentiating cardiomyocytes from human induced pluripotent stem cells (hiPSCs) have unlocked a viable path to creating in vitro cardiac models. Currently, hiPSC-derived
[9] Sticky science: How thicker fluids turn stem cells toward new roles ... — Sticky Science: How Thicker Fluids Turn Stem Cells Toward New Roles - Johns Hopkins Whiting School of Engineering “We found that the viscosity – the thickness – of the fluid around stem cells can have a big impact on how they develop, opening up new possibilities for advancing regenerative medicine,” — Alice Amitrano, doctoral student in the department of chemical and biomolecular engineering “We found that the viscosity – the thickness – of the fluid around stem cells can have a big impact on how they develop, opening up new possibilities for advancing regenerative medicine,” said Alice Amitrano, a doctoral student in the Whiting School of Engineering’s Department of Chemical and Biomolecular Engineering, who led the study with Qinling Yuan, also a doctoral student in the department.
[10] Editorial: Tissue Engineering for Drug Discovery and Personalized Medicine — Recent advances in cell biology, tissue engineering, and microsystem technologies, such as microfluidics and 3D bioprinting, have enabled devising innovative solutions by creating biomimetic physiological tissue structures and environments. ... which aims to boost the development of drug discovery and personalized medicine.
[11] PDF — This article explores how stem cells contribute to the future of personalized medicine, highlighting their potential in developing targeted therapies, understanding disease mechanisms, and enhancing regenerative treatments. Personalized stem cell therapies The field of personalized stem cell therapy is rapidly evolving, with advancements in gene editing technologies such as CRISPR offering the potential to correct genetic defects in patient-derived stem cells. Ensuring equitable access to personalized stem cell therapies is crucial for preventing disparities in healthcare and ensuring that all patients can benefit from advancements in medicine. As we move forward into an era of personalized medicine, a commitment to responsible research, ethical practices, and equitable access will be crucial in shaping a future where all patients can benefit from the advancements in stem cell technologies.
[13] PDF — The intersection of stem cells and personalized medicine holds transformative potential for the future of healthcare. By enabling tailored therapies, improving drug development, and enhancing regenerative treatments, stem cells are poised to revolutionize the way diseases are understood and treated.
[45] The emerging era of cell engineering: Harnessing the ... - Science — The power of cell engineering has been clinically validated by the development of immune cells designed to kill cancer. This same tool kit for rewiring cell connectivity is beginning to be used to engineer cell therapies for a host of other diseases and to program the self-organization of tissues and organs.
[46] PDF — The end of twentieth century and early twenty‐first century brought the progress in 3‐D cell culture technology and created the possibility of the tissue engineering and the regenerative medicine development. Keywords: spontaneous generation, Harrison's hanging drop culture method, HeLa cell line, Hayflick limit, cell culture history
[47] History of Cell Biology - BioExplorer.net — Learn the history of cell biology and timeline from past to present. ... advances in electron microscopy greatly facilitated the development of transfection methods.The process of genetic engineering, or modifying an organism's genetic material either by adding genes or deleting some parts of it, was declared as a separate field in the 1970s
[48] History of Cell Biology: Timeline of Important Discoveries - Bitesize Bio — The history of cell biology and the formation of cell theory involved several key developments and discoveries, including the invention of the compound microscope in 1595, the visualization of cells in cork by Robert Hooke in 1655, and the visualization of live cells under the microscope by Anton van Leeuwenhoek in 1674. In the history of cell biology, there have been many individual scientific discoveries and technological developments, from the invention of the microscope, allowing us to see individual cells, to the discovery of fluorescent proteins and the invention of powerful electron microscopes, allowing us to study the function and structure of cells in greater detail. Further Reading on the History of Cell Biology
[55] Future perspectives on engineered T cells for cancer - Cell Press — Chimeric antigen receptor (CAR) T cell therapy has emerged as a revolutionary treatment for hematological malignancies, but its adaptation to solid tumors is impeded by multiple challenges, particularly T cell dysfunction and exhaustion. The heterogeneity and inhospitableness of the solid tumor microenvironment (TME) contribute to diminished CAR T cell efficacy exhibited by reduced
[56] Stanford infuses first patient with innovative solid tumor therapy — Stanford infuses first patient with innovative solid tumor therapy | Stanford Cancer Institute Stanford Cancer Institute Stanford Cancer Institute Stanford Cancer Institute On January 13, 2025, Stanford treated its first patient with Tecelra, an engineered T cell receptor (TCR) therapy that uses a patient’s own immune cells to target the cancer. Stanford Cancer Institute member Allison Betof Warner, MD, PhD, director of Stanford’s solid tumor cell therapy program, says, “TCR cells are like CAR-T cells in that you engineer a naive T cell to express this receptor, but TCR cells can recognize intracellular antigens rather than just something on the surface of the cell, so it opens up a potentially new type of way to go after cancer cells.”
[57] Top 10 Challenges in Cancer Immunotherapy - Cell Press — In recent years, cancer immunotherapy has become a pillar in the treatment of cancer. Hegde and Chen discuss the top ten challenges facing this field, including the opportunity to optimize both synthetic and endogenous immune approaches and to target different immune suppressive mechanisms specific for each patient with cancer.
[58] Advances in cell therapy: progress and challenges in hematological and ... — Advances in cell therapy: progress and challenges in hematological and solid tumors - ScienceDirect Advances in cell therapy: progress and challenges in hematological and solid tumors Cell engineering advancements, including base editing and dual antigen targeting, improve safety and efficacy across cancer types. Cell-based therapies harness the endogenous ability of the immune system to fight cancer and have shown promising results in the treatment of hematological malignancies. In this review, we examine the challenges and future directions of the most prominent cell-based therapies, including chimeric antigen receptor (CAR)-T cells, tumor-infiltrating lymphocytes (TILs), and natural killer (NK) cells, and emerging modalities. No articles found. For all open access content, the Creative Commons licensing terms apply.
[61] Ethics of Gene Therapy: Balancing Progress and Morality — Adhering to these principles helps navigate the complex ethical landscape of gene manipulation and therapy, facilitating progress while upholding moral values and ensuring responsible advancements in genetic treatment. The ethical implications surrounding gene therapy and genetic manipulation require careful consideration to strike a balance between the potential for progress and the preservation of moral standards. This section aims to critically evaluate the morality of gene manipulation by considering societal values, ethical principles, and the potential consequences of genetic editing. The public’s perspective on the moral and ethical considerations surrounding genetic manipulation and treatment is a critical aspect to consider as we navigate the advancements in gene editing and therapy.
[62] Ethical considerations of gene editing and genetic selection — At the end of the summit, the organizing committee released a statement advising ongoing global engagement and discussion, and outlined their conclusions regarding gene editing: 97 “(i)ntensive basic and preclinical research is clearly needed and should proceed, subject to appropriate legal and ethical rules and oversight…”; “(m)any promising and valuable clinical applications of gene editing are directed at altering genetic sequences only in somatic cells… [and] they can be… evaluated within existing and evolving regulatory frameworks for gene therapy…”; and “(g)ene editing might also be used, in principle, to make genetic alterations in gametes or embryos…” The statement goes on to address the ethical, legal, and scientific questions surrounding germline editing that have yet to be answered, and warns: Tang L, Zeng Y, Du H, Gong M, Peng J, Zhang B, et al CRISPR/Cas9‐mediated gene editing in human zygotes using Cas9 protein.
[63] 3D Bioprinting: Challenges in Commercialization and Clinical Translation — The other important challenge in translation of this technology is the standardization of process parameters. The outcome of bioprinting is very sensitive to a range of process parameters [Citation 22] and any change in the process parameters including the external environment might result in a completely different outcome. Depending on the
[64] The Promise and Challenges of Bioprinting in Healthcare — This technology can create complex tissue structures for medical research, drug testing, and organ transplantation. However, the path to fully functional bioprinted organs is fraught with technical, ethical, and regulatory challenges, making it a challenging technology to overcome for widespread adoption. Advancements in Bioprinting
[86] Top Five Biotech Breakthroughs That Shaped 2023 — This effective tool has catalyzed significant advances in cell engineering, fundamentally changing our approach to genetic manipulation. 2023 marked a historic year for CRISPR, with a groundbreaking achievement with the drug Casgevy: the first clinical approval of CRISPR as a cell-based gene therapy for treating sickle cell disease in the UK
[88] Synthetic biology-inspired cell engineering in diagnosis, treatment and ... — Advertisement Synthetic biology-inspired cell engineering in diagnosis, treatment, and drug development Signal Transduction and Targeted Therapy volume 8, Article number: 112 (2023) Cite this article 8160 Accesses 10 Citations 3 Altmetric Metrics details Subjects Abstract The fast-developing synthetic biology (SB) has provided many genetic tools to reprogram and engineer cells for improved performance, novel functions, and diverse applications. Such cell engineering resources can play a critical role in the research and development of novel therapeutics. This literature review updates the recent advances in biomedical applications, including diagnosis, treatment, and drug development, of SB-inspired cell engineering. Here, we elaborate on various SB-driven cell devices in diagnosis, treatment, and drug development. Also, we address the current and potential future challenges for SB and cell engineering in medical applications.
[95] Synthetic biology and artificial intelligence in crop improvement — Synthetic biology plays a pivotal role in improving crop traits and increasing bioproduction through the use of engineering principles that purposefully modify plants through “design, build, test, and learn” cycles, ultimately resulting in improved bioproduction based on an input genetic circuit (DNA, RNA, and proteins). CRISPR-Cas12 offers significant advantages for crop improvement by enabling precise, targeted gene editing with high efficiency and minimal off-target effects, accelerating the development of crops with desirable traits (Zhang et al., 2024b; Zheng et al., 2024). Zhu Q., Wang B., Tan J., Liu T., Li L., Liu Y.G. Plant Synthetic Metabolic Engineering for Enhancing Crop Nutritional Quality. Zhu Q., Zeng D., Yu S., Cui C., Li J., Li H., Chen J., Zhang R., Zhao X., Chen L., Liu Y.G. From Golden Rice to aSTARice: Bioengineering Astaxanthin Biosynthesis in Rice Endosperm.
[99] Programming gene and engineered-cell therapies with synthetic biology ... — Recent advances in synthetic biology are enabling new gene and engineered-cell therapies. These developments include engineered biological sensors that can detect disease biomarkers such as microRNAs and cell-surface proteins; genetic sensors that respond to exogenous small molecules; and new methods for interacting with various components of the cell—editing DNA, modulating RNA, and
[100] Current applications and future perspective of CRISPR/Cas9 gene editing ... — The first clinical application of CRISPR/Cas9 gene editing was in 2016, when a clinical trial delivered CRISPR gene-edited immune cells to a patient with advanced lung cancer . Yet although CRISPR technology shows great potential in gene editing, its safety remains a concern.
[101] The Potential Revolution of Cancer Treatment with CRISPR Technology — However, there is still much to learn regarding the long-term safety of CRISPR use in vivo, which will have tremendous impact on our ability to implement it in patients for the primary prevention or treatment of cancer. The applications of CRISPR/Cas9 technology are limited by the potential for off-target activity, which could result in
[102] PDF — CRISPR-Cas9 technology provides novel and revolutionary strategies for cancer therapy through accurate genome editing to target the intervention in malignancies. Here, we review the wide varieties of applications for CRISPR/Cas9 in cancer to disrupt oncogenes with clear examples and thorough discussion on improving
[104] CRISPR in cancer biology and therapy - Nature Reviews Cancer — Advertisement View all journals Search Log in Explore content About the journal Publish with us Subscribe Sign up for alerts RSS feed nature nature reviews cancer review articles article Review Article Published: 22 February 2022 CRISPR in cancer biology and therapy Alyna Katti1,2 na1, Bianca J. Diaz ORCID: orcid.org/0000-0002-5309-13001,2 na1, Christina M. Caragine ORCID: orcid.org/0000-0002-5958-72003,4 na1, Neville E. Sanjana ORCID: orcid.org/0000-0002-1504-00273,4 & … Lukas E. Dow ORCID: orcid.org/0000-0001-7048-14181,5 Show authorsNature Reviews Cancer volume 22, pages 259–279 (2022)Cite this article 108k Accesses 281 Altmetric Metrics details Subjects Cancer genetics Cancer genomics Cancer models Genetic engineering Abstract Over the past decade, CRISPR has become as much a verb as it is an acronym, transforming biomedical research and providing entirely new approaches for dissecting all facets of cell biology. In cancer research, CRISPR and related tools have offered a window into previously intractable problems in our understanding of cancer genetics, the noncoding genome and tumour heterogeneity, and provided new insights into therapeutic vulnerabilities. Here, we review the progress made in the development of CRISPR systems as a tool to study cancer, and the emerging adaptation of these technologies to improve diagnosis and treatment.
[113] Advances in CRISPR/Cas-based Gene Therapy in Human Genetic Diseases — Advances in CRISPR/Cas-based Gene Therapy in Human Genetic Diseases - PMC Advances in CRISPR/Cas-based Gene Therapy in Human Genetic Diseases Keywords: CRISPR/Cas, Gene editing, Gene therapy, Human disease, Genetic disease To date, three clinical trials aiming to treat patients with β-thalassemia and severe sickle cell disease by transfusion of CRIPSR/Cas9 edited CD34+ human HSCs (CTX001) have been initiated by CRISPR Therapeutics in 2018 and Allife Medical Science and Technology Co., Ltd in 2019 (Table 3). Similarly, CRISPR/Cas- induced NHEJ has been used to treat DMD in a DMD dog model after AAV-mediated systemic delivery of CRISPR gene editing components.
[114] CRISPR/Cas9 therapeutics: progress and prospects — Advertisement View all journals Search Log in Explore content About the journal Publish with us Sign up for alerts RSS feed nature signal transduction and targeted therapy review articles article CRISPR/Cas9 therapeutics: progress and prospects Download PDF Download PDF Review Article Open access Published: 16 January 2023 CRISPR/Cas9 therapeutics: progress and prospects Tianxiang Li1 na1, Yanyan Yang2 na1, Hongzhao Qi1 na1, Weigang Cui3, Lin Zhang4, Xiuxiu Fu5, Xiangqin He5, Meixin Liu1, Pei-feng Li ORCID: orcid.org/0000-0002-0969-94071 & … Tao Yu1,5 Show authorsSignal Transduction and Targeted Therapy volume 8, Article number: 36 (2023) Cite this article 157k Accesses 34 Altmetric Metrics details Subjects Gene delivery Molecular medicine Abstract Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing technology is the ideal tool of the future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency. However, strategies to effectively deliver the CRISPR system to diseased cells in vivo are currently lacking, and nonviral vectors with target recognition functions may be the focus of future research. Meanwhile, there are still many potential challenges identified when targeting delivery of CRISPR/Cas9 technology for disease treatment. This paper reviews the current developments in three aspects, namely, gene-editing type, delivery vector, and disease characteristics.
[115] Applying switchable Cas9 variants to in vivo gene editing for ... — In addition, recently developed switchable Cas9 variants, whose activity can be controlled by an external stimulus, provide an extra level of spatiotemporal control on gene editing and are particularly desirable for certain applications. Here, we discuss the considerations and difficulties for implementing Cas9 to in vivo gene therapy.
[132] A new era of stem cell and developmental biology: from blastoids to ... — Advertisement View all journals Search Log in Explore content About the journal Publish with us Sign up for alerts RSS feed nature experimental & molecular medicine review articles article A new era of stem cell and developmental biology: from blastoids to synthetic embryos and beyond Download PDF Download PDF Review Article Open access Published: 02 October 2023 A new era of stem cell and developmental biology: from blastoids to synthetic embryos and beyond Yunhee Kim ORCID: orcid.org/0000-0001-5379-77441,2 na1, Inha Kim ORCID: orcid.org/0009-0007-3263-45411,2 na1 & Kunyoo Shin ORCID: orcid.org/0000-0002-1519-98391,2 Experimental & Molecular Medicine volume 55, pages 2127–2137 (2023)Cite this article 16k Accesses 11 Citations 6 Altmetric Metrics details Subjects Disease model Embryogenesis Organogenesis Pattern formation Stem cells Abstract Recent discoveries in stem cell and developmental biology have introduced a new era marked by the generation of in vitro models that recapitulate early mammalian development, providing unprecedented opportunities for extensive research in embryogenesis. Here, we present an overview of current techniques that model early mammalian embryogenesis, specifically noting models created from stem cells derived from two significant species: Homo sapiens, for its high relevance, and Mus musculus, a historically common and technically advanced model organism. At each developmental stage, we present corresponding in vitro models that recapitulate the in vivo embryo and further discuss how these models may be used to model diseases. This review aims to explore developments in stem cell research, focusing on stem cell-based in vitro early embryonic developmental models.
[133] Synthetic biology-inspired cell engineering in diagnosis, treatment and ... — Advertisement Synthetic biology-inspired cell engineering in diagnosis, treatment, and drug development Signal Transduction and Targeted Therapy volume 8, Article number: 112 (2023) Cite this article 8160 Accesses 10 Citations 3 Altmetric Metrics details Subjects Abstract The fast-developing synthetic biology (SB) has provided many genetic tools to reprogram and engineer cells for improved performance, novel functions, and diverse applications. Such cell engineering resources can play a critical role in the research and development of novel therapeutics. This literature review updates the recent advances in biomedical applications, including diagnosis, treatment, and drug development, of SB-inspired cell engineering. Here, we elaborate on various SB-driven cell devices in diagnosis, treatment, and drug development. Also, we address the current and potential future challenges for SB and cell engineering in medical applications.
[134] Advancing cell-based cancer immunotherapy through stem cell engineering — Stem cells and stem cell-derived products have been investigated for diseases such as muscular dystrophy, heart disease, Parkinson's disease, Alzheimer's disease, spinal cord injuries, diabetes, and cancer. 1 Although much work remains to be done, recent advances in stem cell engineering underscore the promise of a new generation of stem
[135] Advancements and challenges in stem cell transplantation for ... — Advancements and challenges in stem cell transplantation for regenerative medicine - ScienceDirect Advancements and challenges in stem cell transplantation for regenerative medicine Stem cell transplantation has emerged as a promising avenue in regenerative medicine, potentially facilitating tissue repair in degenerative diseases and injuries. It explores the identification and isolation of various stem cell types, including embryonic, induced pluripotent, and adult stem cells derived from multiple sources. Additionally, the review highlights the tissue-specific applications of these stem cells, focusing on bone and cartilage regeneration, treatment of neurological disorders, and management of hematological conditions. Stem cell transplantation (Adipose-Derived Stem Cells) (Embryonic Stem Cells) (Limbal Progenitor Stem Cells) (Tissue-Specific Progenitor Stem Cells) For all open access content, the Creative Commons licensing terms apply.
[136] Industry updates from the field of stem cell research and regenerative ... — Collaboration agreement: Mekonos & bit.bio. Mekonos (CA, USA; https://mekonos.com), a biotech platform company building the future of cell therapies on a chip, has announced a new research collaboration with bit.bio (UK; www.bit.bio), a synthetic biology company providing human cells for research, drug discovery and cell therapy [Citation 4].The collaboration will test and optimize non-viral
[151] Drug delivery: advancements and challenges - ScienceDirect — The major challenge for any drug delivery system is biocompatibility and acceptability because interaction of synthetic materials with human body cells is entirely different from biological one. ... the lipophilic nature of the cell membrane prevents hydrophilic solute to ... Liposomal drug delivery systems modify the kinetic and distribution
[152] Cell Membrane-Cloaked Nanotherapeutics for Targeted Drug Delivery — Cell membrane-cloaked nanotherapeutics integrated with the biomimetic features of cell membranes with multifunctional nanoparticles emerged as a future-oriented platform for targeted drug delivery. They can inherently reproduce the biological properties of the source cells and achieve a wide range of functions, such as prolonged circulation
[169] Engineering the next generation of cell-based therapeutics — The widespread clinical translation and commercialization of cell-based therapies are hampered by challenges related to cell source, viability, potency, safety and scalability. Here, Veiseh and
[176] Future perspectives on engineered T cells for cancer — The efficacy of chimeric antigen receptor (CAR) T cells targeting solid tumors is constrained by target heterogeneity, treatment-associated toxicities, and immunosuppressive factors in the tumor microenvironment, such as poor T cell infiltration, metabolic stress, and T cell exhaustion.
[177] Potentiating CAR-T cell function in the immunosuppressive tumor ... — The immunosuppressive tumor microenvironment represents a key challenge for chimeric antigen receptor (CAR) T cells in solid tumors and includes the production of the inhibitory cytokine transforming growth factor β (TGF-β), which limits CAR-T cell persistence and function.
[178] CAR T cell therapy and the tumor microenvironment: Current challenges ... — Another strategy to combat an immunosuppressive TME and increase CAR T cell function is secretion of pro-inflammatory soluble factors, which can reshape the TME for a favorable anti-tumor response. CAR T cells engineered to secrete IL-12 and IL-18 have been shown to stimulate recruitment of pro-inflammatory immune cells such as M1 macrophages
[179] Obstacles posed by the tumor microenvironment to T cell activity: a ... — For example, rather than treating patients with both engineered T cells and checkpoint inhibitors to sustain T cell activity, with the latter impacting endogenous T cells throughout the body as well, it is possible to engineer T cells with both an anti-tumor receptor and altered inhibitory receptor expression simultaneously.
[181] The Role of Endoplasmic Reticulum Stress on Reducing Recombinant ... — The combination of stresses from industrial cell culture environment and recombinant protein production can overwhelm the protein synthesis machinery in the endoplasmic reticulum (ER). This leads to a buildup of improperly folded proteins which induces ER stress. Cells respond to ER stress by activating the Unfolded Protein Response (UPR).
[195] Advances in CAR T cell therapy: antigen selection, modifications, and ... — Advances in CAR T cell therapy: antigen selection, modifications, and current trials for solid tumors - PMC Advances in CAR T cell therapy: antigen selection, modifications, and current trials for solid tumors Approaches to address these areas of concern include modifications to the antigen binding domains of CARs, new methods to discover more cancer-enhanced antigens, enhancements to CAR T structure to allow for better solid tumor infiltration, and gene editing approaches to increase CAR T cell activity (14–20). Through an overview of CAR T structure, classification, modification, and manufacturing followed by an analysis of antigen selection techniques and clinical trials of CAR T cell therapies against identified antigens, we will discuss the current state of CAR T cell therapies in treating solid tumors while also presenting scopes for improvement for current therapeutic limitations and challenges. doi: 10.1016/j.heliyon.2023.e20460 [DOI] [PMC free article] [PubMed] [Google Scholar]
[201] Regulatory challenges for the manufacture and scale-out of autologous ... — The main challenge in manufacturing however is the need to scale-out production of autologous cell therapy products for both multi-centric Phase III studies and for the supply of marketed products to clinical sites in multiple distributed locations, potentially within different regulatory jurisdictions. A debate is needed on the role of regulators and stakeholders in the risk/benefit decisions that surround alternative business models for MTMM autologous cell therapies, specifically concepts such as ‘GMP in a box’ (in which self-contained modules are used to prepare cell based therapeutic products close to clinic or in local production hubs similar to franchised operations) and point-of-care manufacturing. Review Manufacturing models permitting roll out/scale out of clinically led autologous cell therapies: regulatory and scientific challenges for comparability.[Cytotherapy.
[202] CAR-T cell manufacturing landscape—Lessons from the past decade and ... — Dias and colleagues assess in this review the current CAR-T cell manufacturing landscape ... Encouraging innovation requires that regulatory requirements are adjusted to match the reality of academic centers and, in line with this, the EMA recently set up a pilot aiming to support academic and non-profit organizations on the translation of
[203] Emerging technologies and their impact on regulatory science — In 2018, the PMDA established a Regulatory Science Center to act as a command center; this center plays a critical central role in the incorporation of innovation in the regulatory system. This has led to the utilization of clinical trial data and electronic health records for advanced reviews and safety measures and has promoted innovative
[204] Global regulatory progress in delivering on the promise of gene ... — A comparative study of the regulatory submissions for advanced therapy medicinal products (ATMPs) with those for other biologics found that ATMP developers need to comply with more post-approval commitments, which can be a challenge to market performance.6 Furthermore, several non-regulatory issues affect gene therapy access post-approval related to the health technology assessment in some regions, valuation, and payment policies that are beyond the scope of this article. To build on this concept, the WHO recently published a draft working document, which outlines these principles and provides an excellent discussion of principles and considerations.31 While many countries may seek to establish new regulatory frameworks to support gene therapy development, we would recommend a heightened focus on reliance to avoid delays in the introduction of safe and effective products to market.
[205] Tissue Engineering: Current Strategies and Future Directions — These autologous stem cells have the potential to become almost any type of cell in the adult body, and thus would be useful in tissue and organ replacement applications.59 Therefore, therapeutic cloning, which has also been called somatic cell nuclear transfer, may provide an alternative source of transplantable cells. Tissue engineering strategies are often referred to as "growing organs in the laboratory." In these strategies, differentiated cells or stem cells are seeded onto a biomaterial scaffold and this construct is allowed to mature in vitro in a bioreactor for a short time before implantation in vivo.
[207] Regenerative engineering: a review of recent advances and future directions — Regenerative engineering is defined as the convergence of the disciplines of advanced material science, stem cell science, physics, developmental biology and clinical translation for the regeneration of complex tissues and organ systems. Regenerative engineering utilizes the convergence of the disciplines of advanced material science, stem cell science, physics, developmental biology and clinical translation for the regeneration of complex tissues and organ systems . Regenerative engineering utilizes the convergence of the disciplines of advanced material science, stem cell science, physics, developmental biology and clinical translation for the regeneration of complex tissues and organ systems. Regenerative engineering utilizes the convergence of the disciplines of advanced material science, stem cell science and developmental biology to achieve clinical translation for the regeneration of complex tissues and organ system.
[208] Tissue engineering: current status and future perspectives — It is not only now possible to control cells and their environments more precisely but also to engineer living tissues and organs of increasing complexities for potential clinical use. Current challenges facing this field include availability of dependable cell sources, ideal bioinks, reducing the immunogenicity of TE scaffold, engineering vasculature and innervation in bioengineered tissues, commercialization, and regulatory hurdles. Poly(ε-caprolactone) (PCL), a semi-crystalline polyester, has been widely used for tissue engineering and regenerative medicine applications due to its favorable mechanical properties, biocompatibility, and long-term biodegradation. The triad of nanotechnology, cell signalling, and scaffold implantation for the successful repair of damaged organs: An overview on soft-tissue engineering Conductive poly(ε-caprolactone)/polylactic acid scaffolds for tissue engineering applications: Synergy effect of zirconium nanoparticles and polypyrrole
[211] Synthetic developmental biology: build and control multicellular ... — Synthetic biology offers a bottom-up engineering approach that intends to understand complex systems via design-build-test cycles. Embryonic development comprises complex processes that originate at the level of gene regulatory networks in a cell and emerge into collective cellular behaviors with multicellular forms and functions.
[213] iPSC Differentiation: Modern Methods for Tissue-Specific Cells — iPSC Differentiation: Modern Methods for Tissue-Specific Cells - BiologyInsights iPSC Differentiation: Modern Methods for Tissue-Specific Cells Explore modern strategies for differentiating iPSCs into tissue-specific cells, highlighting key pathways, induction methods, and validation techniques. Advancements in signaling pathways, induction methods, and lineage-specific protocols have improved the efficiency and reliability of iPSC differentiation. The orchestration of signaling pathways dictates iPSC differentiation, with specific molecular cues guiding lineage commitment and maturation. During lineage commitment, FGF signaling has dual roles: its activation supports mesodermal and endodermal differentiation, while its inhibition promotes neural induction. For instance, sequential exposure to Activin A, Wnt3a, and keratinocyte growth factor (KGF) enhances hepatic differentiation, yielding hepatocyte-like cells with improved albumin secretion and cytochrome P450 activity. The differentiation of iPSCs into specific cell types follows developmental cues that guide lineage commitment.
[214] Stem Cell Technology in Organ Transplantation: A Novel Method for 3D ... — Modern 3D bioprinting technologies in combination with autologous induced pluripotent stem cells (iPS)-derived grafts could represent a relevant tissue engineering approach to treat end-stage liver disease. Here, we described a novel method for 3D bioprinting functional and stable liver grafts using human iPS-derived cells.
[215] Three-dimensional bioprinting of stem-cell derived tissues for human ... — In order to engineer a realistic tissue model using stem cells as an alternative to human tissue, it is essential to create artificial stem cell microenvironment or niches. Three-dimensional (3D) bioprinting is a promising tissue engineering field that offers new opportunities to precisely place stem cells within their niches layer-by-layer.
[216] Applications of 3D Bioprinted-Induced Pluripotent Stem Cells in ... — Abstract Induced pluripotent stem cell (iPSC) technology and advancements in three-dimensional (3D) bioprinting technology enable scientists to reprogram somatic cells to iPSCs and 3D print iPSC-derived organ constructs with native tissue architecture and function. iPSCs and iPSC-derived cells suspended in hydrogels (bioinks) allow to print tissues and organs for downstream medical