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Effect of Human Umbilical Cord Matrix-Derived Mesenchymal Stem Cells on Bisphosphonate-Related Osteonecrosis of the Jaw
- Source :
- Tissue Eng Regen Med
- Publication Year :
- 2021
-
Abstract
- 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13770-021-00372-x.
- Subjects :
- business.industry
medicine.medical_treatment
Osteoporosis
Mesenchymal stem cell
Biomedical Engineering
Medicine (miscellaneous)
Parathyroid hormone
Cell Differentiation
Mesenchymal Stem Cells
Bisphosphonate
medicine.disease
Mesenchymal Stem Cell Transplantation
Rats
Umbilical Cord
In vivo
medicine
Cancer research
Animals
Humans
Bisphosphonate-Associated Osteonecrosis of the Jaw
Original Article
Stem cell
Bone regeneration
business
Osteonecrosis of the jaw
Subjects
Details
- ISSN :
- 22125469
- Volume :
- 18
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Tissue engineering and regenerative medicine
- Accession number :
- edsair.doi.dedup.....045617aeae676ec91594906547aeea27