The dependence of in vivo stable ectopic chondrogenesis by human mesenchymal stem cells on chondrogenic differentiation in vitro.
In vivo niche plays an important role in determining the fate of implanted mesenchymal stem cells (MSCs) by directing committed differentiation. An inappropriate in vivo niche can also alter desired ultimate fate of exogenous MSCs even they are in vitro induced to express a specific phenotype before in vivo implantation. Studies have shown that in vitro chondrogenically differentiated MSCs are apt to lose their phenotype and fail to form stable cartilage in subcutaneous environment. We hypothesized that failure of maintaining the phenotype of induced MSCs in subcutaneous environment is due to the insufficient chondrogenic differentiation in vitro and fully differentiated MSCs can retain their chondrocyte-like phenotype and form stable ectopic cartilage. To test this hypothesis, extended in vitro chondrogenic induction and cartilage formation were carried out before implantation. Human bone marrow stem cells (hBMSCs) were seeded onto polylactic acid coated polyglycolic acid scaffolds. The cell-scaffold constructs were chondrogenically induced from 4 to 12 weeks for in vitro chondrogenesis, and then implanted subcutaneously into nude mice for 12 or 24 weeks. The engineered cartilages were evaluated by gross view, glycosaminoglycan content measurement, and histological staining before and after implantation. Histological examination showed typical cartilage structure formation after 8 weeks of induction in vitro. However, part of the constructs became ossified after implantation when in vitro induction lasted 8 weeks or less time. In contrast, those induced for 12 weeks in vitro could retain their cartilage structure after in vivo implantation. These results indicate that a fully differentiated stage achieved by extended chondrogenic induction in vitro is necessary for hBMSCs to form stable ectopic chondrogenesis in vivo.
Liu
Kai
K
Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, 639 Zhi Zao Ju Road, Shanghai 200011, PR China.
Zhou
Guang Dong
GD
Liu
Wei
W
Zhang
Wen Jie
WJ
Cui
Lei
L
Liu
Xia
X
Liu
Tian Yi
TY
Cao
Yilin
Y
D000293:Adolescent; D000328:Adult; D000818:Animals; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000166:cytology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology; D020219:Chondrogenesis; D006025:Glycosaminoglycans / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000737:chemistry; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000648:ultrastructure; D051379:Mice; D008819:Mice, Nude; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods
D006025:Glycosaminoglycans; D011091:Polyesters; D011108:Polymers; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)