PMID- 31747961
OWN - NLM
STAT- MEDLINE
DCOM- 20200721
LR  - 20200721
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 10
IP  - 1
DP  - 2019 Nov 20
TI  - Treatment with adipose tissue-derived mesenchymal stem cells exerts anti-diabetic 
      effects, improves long-term complications, and attenuates inflammation in type 2 
      diabetic rats.
PG  - 333
LID - 10.1186/s13287-019-1474-8 [doi]
LID - 333
AB  - BACKGROUND: Long-term diabetes-associated complications are the major causes of 
      morbidity and mortality in individuals with diabetes. These diabetic 
      complications are closely linked to immune system activation along with chronic, 
      non-resolving inflammation, but therapies to directly reverse these complications 
      are still not available. Our previous study demonstrated that mesenchymal stem 
      cells (MSCs) attenuated chronic inflammation in type 2 diabetes mellitus (T2DM), 
      resulting in improved insulin sensitivity and islet function. Therefore, we 
      speculated that MSCs might exert anti-inflammatory effects and promote the 
      reversal of diabetes-induced kidney, liver, lung, heart, and lens diseases in 
      T2DM rats. METHODS: We induced a long-term T2DM complication rat model by using a 
      combination of a low dose of streptozotocin (STZ) with a high-fat diet (HFD) for 
      32 weeks. Adipose-derived mesenchymal stem cells (ADSCs) were systemically 
      administered once a week for 24 weeks. Then, we investigated the role of ADSCs in 
      modulating the progress of long-term diabetic complications. RESULTS: Multiple 
      infusions of ADSCs attenuated chronic kidney disease (CKD), nonalcoholic 
      steatohepatitis (NASH), lung fibrosis, and cataracts; improved cardiac function; 
      and lowered serum lipid levels in T2DM rats. Moreover, the levels of inflammatory 
      cytokines in the serum of each animal group revealed that ADSC infusions were 
      able to not only inhibit pro-inflammatory cytokines IL-6, IL-1beta, and TNF-alpha 
      expression but also increase anti-inflammatory cytokine IL-10 systematically. 
      Additionally, MSCs reduced the number of iNOS(+) M1 macrophages and restored the 
      number of CD163(+) M2 macrophages. CONCLUSIONS: Multiple intravenous infusions of 
      ADSCs produced significant protective effects against long-term T2DM 
      complications by alleviating inflammation and promoting tissue repair. The 
      present study suggests ADSCs may be a novel, alternative cell therapy for 
      long-term diabetic complications.
FAU - Yu, Songyan
AU  - Yu S
AD  - School of Medicine, Nankai University, Tianjin, China.
AD  - Department of Endocrinology, Chinese PLA General Hospital, Medical School of 
      Chinese PLA, Beijing, China.
FAU - Cheng, Yu
AU  - Cheng Y
AD  - Department of Endocrinology, Chinese PLA General Hospital, Medical School of 
      Chinese PLA, Beijing, China.
FAU - Zhang, Linxi
AU  - Zhang L
AD  - Department of Endocrinology and Metabolism, Peking University Third Hospital, 
      Beijing, China.
FAU - Yin, Yaqi
AU  - Yin Y
AD  - Department of Endocrinology, Chinese PLA General Hospital, Medical School of 
      Chinese PLA, Beijing, China.
FAU - Xue, Jing
AU  - Xue J
AD  - Department of Endocrinology, Chinese PLA General Hospital, Medical School of 
      Chinese PLA, Beijing, China.
FAU - Li, Bing
AU  - Li B
AD  - Department of Endocrinology, Chinese PLA General Hospital, Medical School of 
      Chinese PLA, Beijing, China.
FAU - Gong, Zhengyuan
AU  - Gong Z
AD  - Department of Endocrinology, Chinese PLA General Hospital, Medical School of 
      Chinese PLA, Beijing, China.
FAU - Gao, Jieqing
AU  - Gao J
AD  - Department of Endocrinology, Chinese PLA General Hospital, Medical School of 
      Chinese PLA, Beijing, China.
FAU - Mu, Yiming
AU  - Mu Y
AUID- ORCID: 0000-0002-3344-3540
AD  - School of Medicine, Nankai University, Tianjin, China. 
      muyiming@301hospital.com.cn.
AD  - Department of Endocrinology, Chinese PLA General Hospital, Medical School of 
      Chinese PLA, Beijing, China. muyiming@301hospital.com.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191120
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
SB  - IM
MH  - Adipose Tissue/*metabolism/pathology
MH  - Allografts
MH  - Animals
MH  - *Diabetes Mellitus, Experimental/metabolism/pathology/therapy
MH  - *Diabetes Mellitus, Type 2/metabolism/pathology/therapy
MH  - Inflammation/metabolism/pathology/therapy
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC6868748
OTO - NOTNLM
OT  - Diabetes
OT  - Diabetes complications
OT  - Inflammation
OT  - Macrophage
OT  - Mesenchymal stem cells
COIS- The authors declare that they have no competing interests.
EDAT- 2019/11/22 06:00
MHDA- 2020/07/22 06:00
PMCR- 2019/11/20
CRDT- 2019/11/22 06:00
PHST- 2019/05/14 00:00 [received]
PHST- 2019/10/30 00:00 [accepted]
PHST- 2019/09/03 00:00 [revised]
PHST- 2019/11/22 06:00 [entrez]
PHST- 2019/11/22 06:00 [pubmed]
PHST- 2020/07/22 06:00 [medline]
PHST- 2019/11/20 00:00 [pmc-release]
AID - 10.1186/s13287-019-1474-8 [pii]
AID - 1474 [pii]
AID - 10.1186/s13287-019-1474-8 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2019 Nov 20;10(1):333. doi: 10.1186/s13287-019-1474-8.