PMID- 29988034
OWN - NLM
STAT- MEDLINE
DCOM- 20191125
LR  - 20191125
IS  - 2041-4889 (Electronic)
VI  - 9
IP  - 7
DP  - 2018 Jul 9
TI  - Human umbilical cord-derived mesenchymal stem cells direct macrophage 
      polarization to alleviate pancreatic islets dysfunction in type 2 diabetic mice.
PG  - 760
LID - 10.1038/s41419-018-0801-9 [doi]
LID - 760
AB  - Progressive pancreatic beta-cell dysfunction is recognized as a fundamental 
      pathology of type 2 diabetes (T2D). Recently, mesenchymal stem cells (MSCs) have 
      been identified in protection of islets function in T2D individuals. However, the 
      underlying mechanisms remain elusive. It is widely accepted that beta-cell 
      dysfunction is closely related to improper accumulation of macrophages in the 
      islets, and a series of reports suggest that MSCs possess great immunomodulatory 
      properties by which they could elicit macrophages into an anti-inflammatory M2 
      state. In this study, we induced a T2D mouse model with a combination of high-fat 
      diet (HFD) and low-dose streptozotocin (STZ), and then performed human umbilical 
      cord-derived MSCs (hUC-MSCs) infusion to investigate whether the effect of MSCs 
      on islets protection was related to regulation on macrophages in pancreatic 
      islets. hUC-MSCs infusion exerted anti-diabetic effects and significantly 
      promoted islets recovery in T2D mice. Interestingly, pancreatic inflammation was 
      remarkably suppressed, and local M1 macrophages were directed toward an 
      anti-inflammatory M2-like state after hUC-MSC infusion. In vitro study also 
      proved that hUC-MSCs inhibited the activation of the M1 phenotype and induced the 
      generation of the M2 phenotype in isolated mouse bone marrow-derived macrophages 
      (BMDMs), peritoneal macrophages (PMs) and in THP-1 cells. Further analysis showed 
      that M1-stimulated hUC-MSCs increased the secretion of interleukin (IL)-6, 
      blocking which by small interfering RNA (siRNA) largely abrogated the hUC-MSCs 
      effects on macrophages both in vitro and in vivo, resulting in dampened 
      restoration of beta-cell function and glucose homeostasis in T2D mice. In addition, 
      MCP-1 was found to work in accordance with IL-6 in directing macrophage 
      polarization from M1 to M2 state. These data may provide new clues for searching 
      for the target of beta-cell protection. Furthermore, hUC-MSCs may be a superior 
      alternative in treating T2D for their macrophage polarization effects.
FAU - Yin, Yaqi
AU  - Yin Y
AD  - Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
FAU - Hao, Haojie
AU  - Hao H
AD  - Department of Molecular Biology, Institute of Basic Medicine, School of Life 
      Science, Chinese PLA General Hospital, Beijing, China.
FAU - Cheng, Yu
AU  - Cheng Y
AD  - Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
FAU - Zang, Li
AU  - Zang L
AD  - Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
FAU - Liu, Jiejie
AU  - Liu J
AD  - Department of Molecular Biology, Institute of Basic Medicine, School of Life 
      Science, Chinese PLA General Hospital, Beijing, China.
FAU - Gao, Jieqing
AU  - Gao J
AD  - Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
FAU - Xue, Jing
AU  - Xue J
AD  - Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
FAU - Xie, Zongyan
AU  - Xie Z
AD  - Department of Geriatrics, China-Japan Friendship Hospital, Beijing, China.
FAU - Zhang, Qi
AU  - Zhang Q
AD  - Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical 
      University, Beijing, China.
FAU - Han, Weidong
AU  - Han W
AD  - Department of Molecular Biology, Institute of Basic Medicine, School of Life 
      Science, Chinese PLA General Hospital, Beijing, China. hanwdrsw69@yahoo.com.
FAU - Mu, Yiming
AU  - Mu Y
AD  - Department of Endocrinology, Chinese PLA General Hospital, Beijing, China. 
      muyiming@301hospital.com.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180709
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Interleukin-6)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Differentiation/physiology
MH  - Diabetes Mellitus, Type 2/*metabolism/*pathology/therapy
MH  - Flow Cytometry
MH  - Humans
MH  - Interleukin-6/metabolism
MH  - Islets of Langerhans/*metabolism/*pathology
MH  - Macrophages/*cytology
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*cytology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - THP-1 Cells
MH  - Umbilical Cord/*cytology
PMC - PMC6037817
COIS- The authors declare no competing interests.
EDAT- 2018/07/11 06:00
MHDA- 2019/11/26 06:00
PMCR- 2018/07/09
CRDT- 2018/07/11 06:00
PHST- 2017/11/12 00:00 [received]
PHST- 2018/06/01 00:00 [accepted]
PHST- 2018/05/13 00:00 [revised]
PHST- 2018/07/11 06:00 [entrez]
PHST- 2018/07/11 06:00 [pubmed]
PHST- 2019/11/26 06:00 [medline]
PHST- 2018/07/09 00:00 [pmc-release]
AID - 10.1038/s41419-018-0801-9 [pii]
AID - 801 [pii]
AID - 10.1038/s41419-018-0801-9 [doi]
PST - epublish
SO  - Cell Death Dis. 2018 Jul 9;9(7):760. doi: 10.1038/s41419-018-0801-9.