PMID- 34347277
OWN - NLM
STAT- MEDLINE
DCOM- 20220323
LR  - 20230708
IS  - 2212-5469 (Electronic)
IS  - 1738-2696 (Print)
IS  - 1738-2696 (Linking)
VI  - 18
IP  - 6
DP  - 2021 Dec
TI  - Effect of Human Umbilical Cord Matrix-Derived Mesenchymal Stem Cells on 
      Bisphosphonate-Related Osteonecrosis of the Jaw.
PG  - 975-988
LID - 10.1007/s13770-021-00372-x [doi]
AB  - 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.
CI  - (c) 2021. The Korean Tissue Engineering and Regenerative Medicine Society.
FAU - Yang, Gwanghyun
AU  - Yang G
AD  - Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan 
      Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of 
      Korea.
FAU - Kim, Young-Nam
AU  - Kim YN
AD  - Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan 
      Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of 
      Korea.
FAU - Kim, Hyunjeong
AU  - Kim H
AD  - Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan 
      Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of 
      Korea.
FAU - Lee, Bu-Kyu
AU  - Lee BK
AUID- ORCID: 0000-0001-8888-1719
AD  - Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan 
      Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of 
      Korea. bukyu.lee@gmail.com.
AD  - Department of Oral and Maxillofacial Surgery, Asan Medical Center, College of 
      Medicine, University of Ulsan, Seoul, Republic of Korea. bukyu.lee@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210804
PL  - Korea (South)
TA  - Tissue Eng Regen Med
JT  - Tissue engineering and regenerative medicine
JID - 101699923
SB  - IM
MH  - Animals
MH  - *Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy/metabolism
MH  - Cell Differentiation
MH  - Humans
MH  - *Mesenchymal Stem Cell Transplantation/methods
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Rats
MH  - Umbilical Cord
PMC - PMC8599575
OTO - NOTNLM
OT  - Bisphosphonates
OT  - Bone regeneration
OT  - Human umbilical cord
OT  - Hyperparathyroidism
OT  - Mesenchymal stem cells
OT  - Osteonecrosis
COIS- The authors have no financial conflicts of interest.
EDAT- 2021/08/05 06:00
MHDA- 2022/03/24 06:00
PMCR- 2022/08/04
CRDT- 2021/08/04 12:37
PHST- 2021/05/13 00:00 [received]
PHST- 2021/06/25 00:00 [accepted]
PHST- 2021/06/17 00:00 [revised]
PHST- 2021/08/05 06:00 [pubmed]
PHST- 2022/03/24 06:00 [medline]
PHST- 2021/08/04 12:37 [entrez]
PHST- 2022/08/04 00:00 [pmc-release]
AID - 10.1007/s13770-021-00372-x [pii]
AID - 372 [pii]
AID - 10.1007/s13770-021-00372-x [doi]
PST - ppublish
SO  - Tissue Eng Regen Med. 2021 Dec;18(6):975-988. doi: 10.1007/s13770-021-00372-x. 
      Epub 2021 Aug 4.