Effect of Human Umbilical Cord Matrix-Derived Mesenchymal Stem Cells on Bisphosphonate-Related Osteonecrosis of the Jaw.

BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe sequela caused by bisphosphonates (BPs), which are widely used to treat osteoporosis or other malignancies. However, the mechanism underlying BRONJ remains unclear. Recently, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been studied for treatment of diverse diseases and injuries. This study aimed to investigate the therapeutic effects of hUC-MSCs in BRONJ. METHODS: The therapeutic effects of hUC-MSCs were examined in rat bone marrow (rBM)-derived cells using cell viability, colony-forming, and real-time PCR assays and FACS for analyzing essential proinflammatory and bone regeneration markers in vitro. To demonstrate the in vivo therapeutic and adverse effects of transfused hUC-MSCs, micro-CT, H&E staining, IHC (Angiogenesis marker gene expression) staining, and parathyroid hormone (PTH)/calcium assay were conducted in a BRONJ-induced animal model. RESULTS: BP-induced cytotoxicity and inflammation in rBM-derived cells decreased, after co-culture with hUC-MSCs. The expression levels of bone regeneration markers (RUNX2, OSX, and BMP-2) significantly increased in BP-treated rBM-derived cells, after co-culture with hUC-MSCs. The BP-induced abnormal shift in RANKL/OPG expression ratio in rBM-derived cells was normalized by hUC-MSCs. Consistent with these in vitro results, transfused hUC-MSCs markedly decreased BRONJ and significantly healed injured mucosa in the BRONJ-induced animal model. The animals exhibited serious destruction of the kidney structure and increases in serum PTH and calcium levels, which were significantly normalized by hUC-MSC transfusion. CONCLUSION: hUC-MSCs exerted therapeutic effects on BRONJ in vitro and in vivo through their anti-cytotoxicity, anti-inflammatory activity and ability to recover bone regeneration.

Therapeutic effect of mesenchymal stem cells derived from human umbilical cord in rabbit temporomandibular joint model of osteoarthritis.

Osteoarthritis (OA) is a degenerative condition of the temporomandibular joint (TMJ) characterised by chronic inflammation and damage to joint structures. Because of the complexity of TMJ-OA, only symptomatic treatments are currently available. Recent reports have shown that many of stem cells can exert anti-inflammatory and tissue-regenerating effects. In this study, we investigated the potential cartilage-regenerating and anti-inflammatory effects of human umbilical cord matrix-mesenchymal stem cells (hUCM-MSCs) for the treatment of TMJ-OA. hUCM-MSC lines, isolated from different donors, which showed different activities in vitro. Using a selected cell line, we used different concentrations of hUCM-MSCs to assess therapeutic effects in a rabbit model of monosodium iodoacetate-induced TMJ-OA. Compared with the untreated control group, the potential regenerative result and anti-inflammatory effects of hUCM-MSCs were evident at all the tested concentrations in rabbits with induced TMJ-OA. The median dose of hUCM-MSCs showed the prominent cartilage protective effect and further cartilage regeneration potential. This effect occurred via upregulated expression of growth factors, extracellular matrix markers, and anti-inflammatory cytokines, and reduced expression of pro-inflammatory cytokines. The anti-inflammatory effect of hUCM-MSCs was comparable to that of dexamethasone (DEX). However, only hUCM-MSCs showed potential chondrogenesis effects in this study. In conclusion, our results indicate that hUCM-MSCs may be an effective treatment option for the treatment of TMJ-OA.