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Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells

Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells,10.1016/j.biomaterials.2010.05.064,Biomat

Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells   (Citations: 7)
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Human embryonic stem cells (hESCs) have the potential to offer a virtually unlimited source of chondrogenic cells for use in cartilage repair and regeneration. We have recently shown that expandable chondrogenic cells can be derived from hESCs under selective growth factor-responsive conditions. In this study, we explore the potential of these hESC-derived chondrogenic cells to produce an extracellular matrix (ECM)-enriched cartilaginous tissue construct when cultured in hyaluronic acid (HA)-based hydrogel, and further investigated the long-term reparative ability of the resulting hESC-derived chondrogenic cell-engineered cartilage (HCCEC) in an osteochondral defect model. We hypothesized that HCCEC can provide a functional template capable of undergoing orderly remodeling during the repair of critical-sized osteochondral defects (1.5 mm in diameter, 1 mm depth into the subchondral bone) in a rat model. In the process of repair, we observed an orderly spatial-temporal remodeling of HCCEC over 12 weeks into osteochondral tissue, with characteristic architectural features including a hyaline-like neocartilage layer with good surface regularity and complete integration with the adjacent host cartilage and a regenerated subchondral bone. By 12 weeks, the HCCEC-regenerated osteochondral tissue resembled closely that of age-matched unoperated native control, while only fibrous tissue filled in the control defects which left empty or treated with hydrogel alone. Here we demonstrate that transplanted hESC-derived chondrogenic cells maintain long-term viability with no evidence of tumorigenicity, providing a safe, highly-efficient and practical strategy of applying hESCs for cartilage tissue engineering.
Journal: Biomaterials , vol. 31, no. 27, pp. 6968-6980, 2010
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    • ... Scaffold-mediated improvement in cell retention and short-term survival does not necessarily indicate long-term survival of transplanted cell...

    Thomas P Kraehenbuehlet al. Three-dimensional biomaterials for the study of human pluripotent stem...

    • ...Similarly in hESCs, chondrogenic cells isolated from high-density micromass cultures of EBs demonstrated fibrocartilage tissue formation in the pellet system, but displayed hyaline-like cartilaginous tissue formation in the hyaluronic acid hydrogel system [109]...
    • ...HA-based hydrogels Derivation of chondrogenic cell lines prior to encapsulation in hydrogels for implantation Hyaline-like cartilage formation, no teratoma Osteochondral defect Toh et al. 2010 [109] Stem Cell Rev and Rep (2011) 7:544–559 551...
    • ...When tissue-engineered cartilage constructs based on hESC-derived chondrogenic cells were implanted into osteochondral defects in an adult rat model, an orderly remodeling of the cartilage implant into osteochondral tissue to repair the defects was observed [109]...
    • ...By 12 weeks, the regenerated osteochondral tissue resembled closely that of age-matched unoperated native control, while only fibrous tissue filled in the control defects which left empty or treated with hydrogel alone [109]...
    • ...In this instance, it is likely that hESCderived chondrogenic cells exerted a dual function: they provided cells for the repair tissue and may have a stimulatory paracrine effect, which promotes ingrowth of endogenous cells for cartilage repair [109]...
    • ...We have also noted in our study using hESC-derived chondrogenic cells for cartilage repair, an increase in macrophage infiltration into the defect site transplanted with tissue-engineered cartilage graft, which presence was observed throughout the remodeling process of cartilage restoration and subchondral bone regeneration [109]...

    Wei Seong Tohet al. Potential of Human Embryonic Stem Cells in Cartilage Tissue Engineerin...

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