Adult stem cell driven genesis of human-shaped articular condyle.
Uniform design of synovial articulations across mammalian species is challenged by their common susceptibility to joint degeneration. The present study was designed to investigate the possibility of creating human-shaped articular condyles by rat bone marrow-derived mesenchymal stem cells (MSCs) encapsulated in a biocompatible poly(ethylene glycol)-based hydrogel. Rat MSCs were harvested, expanded in culture, and treated with either chondrogenic or osteogenic supplements. Rat MSC-derived chondrogenic and osteogenic cells were loaded in hydrogel suspensions in two stratified and yet integrated hydrogel layers that were sequentially photopolymerized in a human condylar mold. Harvested articular condyles from 4-week in vivo implantation demonstrated stratified layers of chondrogenesis and osteogenesis. Parallel in vitro experiments using goat and rat MSCs corroborated in vivo data by demonstrating the expression of chondrogenic and osteogenic markers by biochemical and mRNA analyses. Ex vivo incubated goat MSC-derived chondral constructs contained cartilage-related glycosaminoglycans and collagen. By contrast, goat MSC-derived osteogenic constructs expressed alkaline phosphatase and osteonectin genes, and showed escalating calcium content over time. Rat MSC-derived osteogenic constructs were stiffer than rat MSC-derived chondrogenic constructs upon nanoindentation with atomic force microscopy. These findings may serve as a primitive proof of concept for ultimate tissue-engineered replacement of degenerated articular condyles via a single population of adult mesenchymal stem cells.
Alhadlaq
Adel
A
Tissue Engineering Laboratory, Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612, USA.
Elisseeff
Jennifer H
JH
Hong
Liu
L
Williams
Christopher G
CG
Caplan
Arnold I
AI
Sharma
Blanka
B
Kopher
Ross A
RA
Tomkoria
Sara
S
Lennon
Donald P
DP
Lopez
Aurora
A
Mao
Jeremy J
JJ
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology; D020219:Chondrogenesis / Q000502:physiology; D004548:Elasticity; D006041:Goats; D006244:Hardness; D006801:Humans; D008297:Male; D008335:Mandibular Condyle / Q000166:cytology* / Q000254:growth & development*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*