Derivation of chondrogenically-committed cells from human embryonic cells for cartilage tissue regeneration.
BACKGROUND
Heterogeneous and uncontrolled differentiation of human embryonic stem cells (hESCs) in embryoid bodies (EBs) limits the potential use of hESCs for cell-based therapies. More efficient strategies are needed for the commitment and differentiation of hESCs to produce a homogeneous population of specific cell types for tissue regeneration applications.


RESULTS
We report here that significant chondrocytic commitment of feeder-free cultured human embryonic stem cells (FF-hESCs), as determined by gene expression and immunostaining analysis, was induced by co-culture with primary chondrocytes. Furthermore, a dynamic expression profile of chondrocyte-specific genes was observed during monolayer expansion of the chondrogenically-committed cells. Chondrogenically-committed cells synergistically responded to transforming growth factor-beta1 (TGF-beta1) and beta1-integrin activating antibody by increasing tissue mass in pellet culture. In addition, when encapsulated in hydrogels, these cells formed cartilage tissue both in vitro and in vivo. In contrast, the absence of chondrocyte co-culture did not result in an expandable cell population from FF-hESCs.


CONCLUSIONS
The direct chondrocytic commitment of FF-hESCs can be induced by morphogenetic factors from chondrocytes without EB formation and homogenous cartilage tissue can be formed in vitro and in vivo.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
Nathaniel S
NS
Hwang
Shyni
S
Varghese
Jennifer
J
Elisseeff
D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000196:embryology / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D017690:Cell Transplantation; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology; D020869:Gene Expression Profiling; D006801:Humans; D020100:Hydrogels; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D020100:Hydrogels; D019012:Integrin beta1; D053773:Transforming Growth Factor beta1