Morphogenetic signals from chondrocytes promote chondrogenic and osteogenic differentiation of mesenchymal stem cells.
Mesenchymal stem cells (MSCs) are potentially useful cells for musculoskeletal tissue engineering. However, controlling MSC differentiation and tissue formation in vivo remains a challenge. There is a significant need for well-defined and efficient protocols for directing MSC behaviors in vivo. We hypothesize that morphogenetic signals from chondrocytes may regulate MSC differentiation. In micromass culture of MSCs, incubation with chondrocyte-conditioned medium (CCM) significantly enhanced the production of cartilage specific matrix including type II collagen. In addition, incubation of MSCs with conditioned medium supplemented with osteogenic factors induced more osteogenesis and accumulation of calcium and increased ALP activity. These findings reveal that chondrocyte-secreted factors promote chondrogenesis as well as osteogenesis of MSCs during in vitro micromass culture. Moreover, when MSCs expanded with chondrocyte-conditioned medium were encapsulated in hydrogels and subsequently implanted into athymic mice, basophilic extracellular matrix deposition characteristic of neocartilage was evident. These results indicate that articular chondrocytes produce suitable morphogenetic factors that induce the differentiation program of MSCs in vitro and in vivo.
Hwang
Nathaniel S
NS
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Varghese
Shyni
S
Puleo
Christopher
C
Zhang
Zijun
Z
Elisseeff
Jennifer
J
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002356:Cartilage / Q000166:cytology / Q000254:growth & development*; D002417:Cattle; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D020219:Chondrogenesis; D024043:Collagen Type II / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D020100:Hydrogels; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010012:Osteogenesis; D019899:Paracrine Communication; D011509:Proteoglycans / Q000378:metabolism; D015398:Signal Transduction; D023822:Tissue Engineering / Q000379:methods
D024043:Collagen Type II; D017077:Culture Media, Conditioned; D006025:Glycosaminoglycans; D020100:Hydrogels; D011509:Proteoglycans; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase; D002118:Calcium