Chondrogenic Derivatives of Embryonic Stem Cells Seeded into 3D Polycaprolactone Scaffolds Generated Cartilage TissueIn Vivo

Abstract

In spite of recent scientific advances, treatment and repair of cartilage using tissue engineering techniques remains challenging. The major constraint is the limited proliferative capacity of mature autologous chondrocytes used in the tissue engineering approach. This problem can be addressed by using stem cells, which can self-renew with greater proliferative potential. Cartilage tissue engineering using adult mesenchymal stem cells derived from bone marrows has met with limited success. In this study we explored cartilage tissue generation from embryonic stem cells (ESCs). ESCs were induced to differentiate into chondroprogenitors, capable of proliferating and subsequently differentiating into cartilage-producing cells. The chondrogenic cells expressed chondrocyte-specific markers and deposited extracellular matrix proteins, proteoglycans. ESC-derived chondrogenic cells and polycaprolactone scaffolds seeded with these cells implanted in mice (129 SvImJ) generated cartilage tissue in vivo. Postimplant analysis of the retrieved tissues demonstrated cartilage-like tissue formation in 3-4 weeks. The cells of retrieved tissues also expressed the chondrocyte-specific marker collagen II. These findings suggest that ESCs can be used for tissue engineering and cultivation of cartilage tissues.

Neonatal Desensitization Supports Long-Term Survival and Functional Integration of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Rat Joint Cartilage Without Immunosuppression

“…Previous studies have reported that implantation of ESCs or ESC-derived chondrogenic cells promoted cartilage repair in vivo [4][5][6]. However, it is difficult to obtain autologous ESCs for cell transplantation, and an immunologic barrier prevents in vivo long-term engraftment and function of allogenous ESCs [7].…”

Generating Cartilage Repair from Pluripotent Stem Cells

“…118 EB-derived hESCs seeded onto polycaprolactone scaffolds did not yield a high density of chondrogenic cells, 119 while hiPSCs from OA patient-derived synovial cells have been shown to form cartilage in a 3D PCA scaffold. 120 An alternative is to use natural or synthetic hydrogels in which the cells can be homogenously distributed before gel polymerisation and that are highly permeable though lacking in the strength under load of rigid scaffolds.…”

From Pluripotent Stem Cells to Lineage-Specific Chondrocytes: Essential Signalling and Cellular Intermediates

“…In another example, a scaffold made from polycaprolactone (PCL) was used. EBs were formed in a serum-containing medium including retinoic acid, then outgrowth culture was performed in a serum-containing chondrogenic medium, and the outgrowth cells were seeded onto the PCL scaffold (Fecek et al, 2008). Implantation of the resulting constructs yielded a poor result, with only a few chondrocyte clusters inside.…”