Adult Stem Cell Driven Genesis of Human-Shaped Articular Condyle

Abstract

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.

Engineering osteochondral constructs through spatial regulation of endochondral ossification

“…Motivated by the fact that no biological based therapies exist to treat patients with osteoarthritis a number of studies have investigated engineering anatomically accurate osteochondral grafts for joint condyle repair [21][22][65][66]. The endochondral approach described in this study may be a powerful tool in scaling-up the osseous phase of such grafts as it is possible to engineer large cartilaginous grafts in vitro using MSCs as the low oxygen conditions that develop within these constructs supports chondrogenic differentiation and the functional development of the engineered tissue [57].…”

“…A number of strategies have been implemented to engineer osteochondral constructs including bi-phasic scaffolding [6][7][8][9][10][11][12], bioreactor technologies [13][14][15][16], and growth factor/gene delivery [17][18][19][20]. Engineered anatomically accurate osteochondral grafts have also been suggested as a potential approach to joint condyle repair [21][22].…”

Modulation of endochondral development of the distal femoral condyle by mechanical loading

“…1 Recent tissue-engineering experiments have demonstrated a high level of plasticity of differentiation of mesenchymal stem cells into osteoblasts. [43][44][45] It is then probable that in this case, the canal-like structures may radiate from the secondary ossification center outwards toward the perichondrium. Further experiments using serial observation/reconstruction methods and/or analysis of the expression of angiogenic and other matrix markers are necessary to determine the mechanisms of mechanically induced SOC formation ex vivo.…”

Engineering custom-designed osteochondral tissue grafts

“…This technique was further advanced by generating the osteogenic and chondrogenic regions from a single cell source [47][48][49]. Bone-marrow-derived rat mesenchymal stem cells (rMSCs) were isolated and induced into chondrogenic and osteogenic lineages during monolayer expansion.…”