Comparison of biological characteristics of human adipose- and umbilical cord- derived mesenchymal stem cells and their effects on delaying the progression of osteoarthritis in a rat model.

ABSTRACT

BACKGROUND: The prevalence of osteoarthritis (OA) is constantly increasing with age. Adipose-derived (AD-) and umbilical cord-derived (UC-) mesenchymal stem cells (MSCs) are attractive alternatives in OA therapy and regenerative medicine. However, whether there are differences in the efficacy of MSCs derived from different tissues in the cartilage regeneration, and the frequency of administration of MSCs needs to be further studied. EXPERIMENT UC-MSCs and AD-MSC were isolated from the umbilical cord and subcutaneous fatty tissue of humans respectively and identified by flow cytometry. In vitro, the proliferation ability and chondrogenic potential of AD-MSCs and UC-MSCs were analyzed. In vivo, forty-three Sprague-Dawley rats were used for the OA model induced by ACLT surgery. OA rats were divided into a sham group, an ACLT model group, and two therapy groups (treated with AD-MSCs or UC-MSCs). Therapy groups were treated using a single or repeated twice injection of AD-MSCs and UC-MSCs at a concentration of 1.0 × 106 cells and were followed up for 12 weeks. Serial sections of knees were examined for histological, immunohistochemical and TUNEL analysis. RESULTS: We demonstrated that the proliferation of UC-MSCs was higher than that of AD-MSCs, consistent with the bigger pellets from UC-MSCs in a chondrogenic induction medium. Degeneration of articular cartilage was observed in histological appearance of Safranine O and Toluidine blue staining, and quantitative results of modified Mankin's Score. Importantly, both AD-MSCs and UC-MSCs transplantation significantly attenuated ACLT surgical-induced OA development. In addition, ACLT-induced reduction in cartilage extracellular matrix synthesis (aggrecan) was significantly suppressed by AD-MSCs or UC-MSCs transplantation. TUNEL assay showed that AD-MSCs and UC-MSCs treatments significantly protected chondrocytes against apoptosis compared with the ACLT group. No significant differences were observed between single injections and repeated twice injections. CONCLUSIONS: The current study suggested that, in vitro, AD-MSCs and UC-MSCs showed a comparable chondrogenic potential, although UC-MSCs displayed a superior proliferation capacity. Furthermore, our results confirmed that the injection of AD-MSCs and UC-MSCs, either single or repeated twice, could significantly inhibit the progression of ACLT-induced osteoarthritis with a similar effect, and MSCs transplantation can decrease the apoptosis of articular chondrocytes caused by ACLT.