PMID- 33736932
OWN - NLM
STAT- MEDLINE
DCOM- 20211015
LR  - 20211015
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Linking)
VI  - 23
IP  - 6
DP  - 2021 Jun
TI  - Reversion of early- and late-stage beta-cell dedifferentiation by human umbilical 
      cord-derived mesenchymal stem cells in type 2 diabetic mice.
PG  - 510-520
LID - S1465-3249(21)00030-X [pii]
LID - 10.1016/j.jcyt.2021.01.005 [doi]
AB  - BACKGROUND AIMS: The authors aimed to observe beta-cell dedifferentiation in type 2 
      diabetes mellitus (T2DM) and investigate the reversal effect of umbilical 
      cord-derived mesenchymal stem cells (UC-MSCs) on early- and late-stage beta-cell 
      dedifferentiation. METHODS: In high-fat diet (HFD)/streptozotocin (STZ)-induced 
      T2DM mice, the authors examined the predominant role of beta-cell dedifferentiation 
      over apoptosis in the development of T2DM and observed the reversion of beta-cell 
      dedifferentiation by UC-MSCs. Next, the authors used db/db mice to observe the 
      progress of beta-cell dedifferentiation from early to late stage, after which UC-MSC 
      infusions of the same amount were performed in the early and late stages of 
      dedifferentiation. Improvement in metabolic indices and restoration of beta-cell 
      dedifferentiation markers were examined. RESULTS: In HFD/STZ-induced T2DM mice, 
      the proportion of beta-cell dedifferentiation was much greater than that of 
      apoptosis, demonstrating that beta-cell dedifferentiation was the predominant 
      contributor to T2DM. UC-MSC infusions significantly improved glucose homeostasis 
      and reversed beta-cell dedifferentiation. In db/db mice, UC-MSC infusions in the 
      early stage significantly improved glucose homeostasis and reversed beta-cell 
      dedifferentiation. In the late stage, UC-MSC infusions mildly improved glucose 
      homeostasis and partially reversed beta-cell dedifferentiation. Combining with other 
      studies, the authors found that the reversal effect of UC-MSCs on beta-cell 
      dedifferentiation relied on the simultaneous relief of glucose and lipid 
      metabolic disorders. CONCLUSIONS: UC-MSC therapy is a promising strategy for 
      reversing beta-cell dedifferentiation in T2DM, and the reversal effect is greater in 
      the early stage than in the late stage of beta-cell dedifferentiation.
CI  - Copyright (c) 2021 International Society for Cell & Gene Therapy. Published by 
      Elsevier Inc. All rights reserved.
FAU - Li, Bing
AU  - Li B
AD  - Department of Endocrinology, First Medical Center of People's Liberation Army 
      General Hospital, Beijing, China.
FAU - Cheng, Yu
AU  - Cheng Y
AD  - Department of Endocrinology, First Medical Center of People's Liberation Army 
      General Hospital, Beijing, China.
FAU - Yin, Yaqi
AU  - Yin Y
AD  - Department of Endocrinology, First Medical Center of People's Liberation Army 
      General Hospital, Beijing, China.
FAU - Xue, Jing
AU  - Xue J
AD  - Department of Endocrinology, First Medical Center of People's Liberation Army 
      General Hospital, Beijing, China.
FAU - Yu, Songyan
AU  - Yu S
AD  - Department of Endocrinology, First Medical Center of People's Liberation Army 
      General Hospital, Beijing, China.
FAU - Gao, Jieqing
AU  - Gao J
AD  - Department of Endocrinology, Beijing Rehabilitation Hospital of Capital Medical 
      University, Beijing, China.
FAU - Liu, Jiejie
AU  - Liu J
AD  - Department of Molecular Biology, Institute of Basic Medicine, School of Life 
      Science, People's Liberation Army General Hospital, Beijing, China.
FAU - Zang, Li
AU  - Zang L
AD  - Department of Endocrinology, First Medical Center of People's Liberation Army 
      General Hospital, Beijing, China. Electronic address: lzang301@163.com.
FAU - Mu, Yiming
AU  - Mu Y
AD  - Department of Endocrinology, First Medical Center of People's Liberation Army 
      General Hospital, Beijing, China. Electronic address: 
      muyiming@301hospital.com.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210316
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
SB  - IM
MH  - Animals
MH  - Cell Dedifferentiation
MH  - *Diabetes Mellitus, Experimental/therapy
MH  - *Diabetes Mellitus, Type 2/therapy
MH  - Humans
MH  - *Mesenchymal Stem Cell Transplantation
MH  - *Mesenchymal Stem Cells
MH  - Mice
MH  - Umbilical Cord
OTO - NOTNLM
OT  - cell transplantation
OT  - mesenchymal stem cells
OT  - type 2 diabetes mellitus
OT  - beta-cell dedifferentiation
EDAT- 2021/03/20 06:00
MHDA- 2021/10/16 06:00
CRDT- 2021/03/19 06:11
PHST- 2020/07/07 00:00 [received]
PHST- 2021/01/11 00:00 [revised]
PHST- 2021/01/20 00:00 [accepted]
PHST- 2021/03/20 06:00 [pubmed]
PHST- 2021/10/16 06:00 [medline]
PHST- 2021/03/19 06:11 [entrez]
AID - S1465-3249(21)00030-X [pii]
AID - 10.1016/j.jcyt.2021.01.005 [doi]
PST - ppublish
SO  - Cytotherapy. 2021 Jun;23(6):510-520. doi: 10.1016/j.jcyt.2021.01.005. Epub 2021 
      Mar 16.