Mesenchymal stem cells in bone development, bone repair, and skeletal regenaration therapy

TLDR

Mesenchymal stem cells (MSCs) are progenitor cells that differentiate into bone, cartilage, tendon, ligament, and muscle through a complex, multistep process regulated by bioactive factors and environmental cues, and understanding this differentiation underlies emerging MSC‑based therapies. The study aims to develop novel protocols for treating clinically challenging conditions by isolating and expanding autologous human MSCs in vitro. This is achieved by isolating MSCs from patients and expanding them mitotically in culture to produce sufficient cells for therapeutic use. The expanded MSCs can repair local bone defects when delivered site‑directed in a carrier vehicle, and may also treat systemic conditions such as osteoporosis through systemic administration or biopharmaceutical approaches targeting key regulatory molecules.

Abstract

Abstract Bone formation in the embryo, and during adult fracture repair and remodeling, involves the progreny of a small number of cells called mesenchymal stem cells (MSCs). These cells continuously replicate themselves, while a portion become committed to mesenchymal cell lineages such as bone, cartilage, tendon, legament and muscle. The differentiation of these cells, within each lineage, is a complex multistep pathway involving discrete cellular trasitions much like that which occurs during hematopoiesys. Progression from one stage to the next depends on the presence of specific bioactive factors, nutrients, and other environmental cues whose exquisitely controlled contributions orchestrate the entire differentiation phgenomenon. As understanding of the cellular and molecular events of osteogenic differentiation of MSCs provides the foundation for the emergence of a new therapeutic technilogy for cell therapy. The isolation and in vitro mitotic expansion of autologous human MSCs will support the development of novel protocols for the treatment of many clinically challenging conditions. For example, local bone defects can be repaired through site‐directed delivery of MSCs in an appropriate carrier vehicle. Generalized conditions, such as osteoporosis, may be treatable by systemic administration of culture‐expanded autologous MSCs or through biopharmaceutical regimens based on the discovery of critical regulatory molecules in the differentiation process. With this in mind, we can begin to explore therapeutic options that have never before been available.