title: Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells.
abstract: 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.
authors.affiliation: Stem Cell Laboratory, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, 11 Lower Kent Ridge Road, Singapore 119083, Singapore.
authors.forename: Wei Seong
authors.initials: WS
authors.lastname: Toh
authors.forename: Eng Hin
authors.initials: EH
authors.lastname: Lee
authors.forename: Xi-Min
authors.initials: XM
authors.lastname: Guo
authors.forename: Jerry K Y
authors.initials: JK
authors.lastname: Chan
authors.forename: Chen Hua
authors.initials: CH
authors.lastname: Yeow
authors.forename: Andre B
authors.initials: AB
authors.lastname: Choo
authors.forename: Tong
authors.initials: T
authors.lastname: Cao
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology*; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology*; D053595:Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D016513:Mice, SCID; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods; D014945:Wound Healing / Q000502:physiology; D055114:X-Ray Microtomography
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid