In vivo commitment and functional tissue regeneration using human embryonic stem cell-derived mesenchymal cells

TLDR

Regenerative medicine with hESCs demands easily expandable cell populations capable of forming functional 3D tissue in vivo, and embryonic‑derived cells offer promising potential for musculoskeletal regeneration due to limited available sources. The study aims to develop and characterize an efficient method for deriving mesenchymal stem cells from hESCs with multilineage differentiation potential for fat, cartilage, and bone production in vitro. The authors derived hESC‑derived MSCs using an efficient protocol, characterized their multilineage potential, and demonstrated their survival and chondrogenic commitment in a hydrogel‑based microenvironment enriched with chondrocyte‑secreted morphogens. Treatment with chondrogenically‑committed hESC‑derived MSCs restored normal cartilage architecture in rat osteochondral defects.

Abstract

Development of clinically relevant regenerative medicine therapies using human embryonic stem cells (hESCs) requires production of a simple and readily expandable cell population that can be directed to form functional 3D tissue in an in vivo environment. We describe an efficient derivation method and characterization of mesenchymal stem cells (MSCs) from hESCs (hESCd-MSCs) that have multilineage differentiation potential and are capable of producing fat, cartilage, and bone in vitro. Furthermore, we highlight their in vivo survival and commitment to the chondrogenic lineage in a microenvironment comprising chondrocyte-secreted morphogenetic factors and hydrogels. Normal cartilage architecture was established in rat osteochondral defects after treatment with chondrogenically-committed hESCd-MSCs. In view of the limited available cell sources for tissue engineering applications, these embryonic-derived cells show significant potential in musculoskeletal tissue regeneration applications.