PMID- 35012642
OWN - NLM
STAT- MEDLINE
DCOM- 20220323
LR  - 20220531
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 13
IP  - 1
DP  - 2022 Jan 10
TI  - Thymosin beta-4 improves endothelial function and reparative potency of diabetic 
      endothelial cells differentiated from patient induced pluripotent stem cells.
PG  - 13
LID - 10.1186/s13287-021-02687-x [doi]
LID - 13
AB  - BACKGROUND: Prior studies show that signature phenotypes of diabetic human 
      induced pluripotent stem cells derived endothelial cells (dia-hiPSC-ECs) are 
      disrupted glycine homeostasis, increased senescence, impaired mitochondrial 
      function and angiogenic potential as compared with healthy hiPSC-ECs. In the 
      current study, we aimed to assess the role of thymosin beta-4 (Tb-4) on endothelial 
      function using dia-hiPSC-ECs as disease model of endothelial dysfunction. METHODS 
      AND RESULTS: Using dia-hiPSC-ECs as models of endothelial dysfunction, we 
      determined the effect of Tb-4 on cell proliferation, senescence, cyto-protection, 
      protein expression of intercellular adhesion molecule-1 (ICAM-1), secretion of 
      endothelin-1 and MMP-1, mitochondrial membrane potential, and cyto-protection in 
      vitro and angiogenic potential for treatment of ischemic limb disease in a mouse 
      model of type 2 diabetes mellitus (T2DM) in vivo. We found that 600 ng/mL Tb4 
      significantly up-regulated AKT activity and Bcl-XL protein expression, enhanced 
      dia-hiPSC-EC viability and proliferation, limited senescence, reduced 
      endothelin-1 and MMP-1 secretion, and improved reparative potency of 
      dia-hiPSC-ECs for treatment of ischemic limb disease in mice with T2DM. However, 
      Tb4 had no effect on improving mitochondrial membrane potential and glycine 
      homeostasis and reducing intercellular adhesion molecule-1 protein expression in 
      dia-hiPSC-ECs. CONCLUSIONS: Tb-4 improves endothelial dysfunction through 
      enhancing hiPSC-EC viability, reducing senescence and endothelin-1 production, 
      and improves angiogenic potency in diabetes.
CI  - (c) 2022. The Author(s).
FAU - Su, Liping
AU  - Su L
AD  - National Heart Research Institute Singapore, National Heart Centre Singapore, 
      Singapore, 169609, Singapore.
FAU - Kong, Xiaocen
AU  - Kong X
AD  - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing, 210029, China.
FAU - Loo, Szejie
AU  - Loo S
AD  - National Heart Research Institute Singapore, National Heart Centre Singapore, 
      Singapore, 169609, Singapore.
FAU - Gao, Yu
AU  - Gao Y
AD  - Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, 200127, China.
FAU - Liu, Bingli
AU  - Liu B
AD  - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing, 210029, China.
FAU - Su, Xiaofei
AU  - Su X
AD  - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing, 210029, China.
FAU - Dalan, Rinkoo
AU  - Dalan R
AD  - Department of Endocrinology, Tan Tock Seng Hospital, Lee Kong Chian School of 
      Medicine, Nanyang Technological University, Singapore, Singapore.
FAU - Ma, Jianhua
AU  - Ma J
AD  - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing, 210029, China. majianhua@china.com.
FAU - Ye, Lei
AU  - Ye L
AUID- ORCID: 0000-0001-5039-6224
AD  - National Heart Research Institute Singapore, National Heart Centre Singapore, 
      Singapore, 169609, Singapore. yeleislp@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220110
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 549LM7U24W (thymosin beta(4))
RN  - 61512-21-8 (Thymosin)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Endothelial Cells/drug effects/metabolism
MH  - Humans
MH  - *Induced Pluripotent Stem Cells/drug effects/metabolism
MH  - Mice
MH  - *Thymosin/genetics/pharmacology
PMC - PMC8751378
OTO - NOTNLM
OT  - Endothelial function
OT  - Endothelium
OT  - Mitochondrial function
OT  - Senescence
OT  - Thymosin
COIS- The authors declare that they have no competing interests.
EDAT- 2022/01/12 06:00
MHDA- 2022/03/24 06:00
PMCR- 2022/01/10
CRDT- 2022/01/11 05:56
PHST- 2021/10/14 00:00 [received]
PHST- 2021/12/17 00:00 [accepted]
PHST- 2022/01/11 05:56 [entrez]
PHST- 2022/01/12 06:00 [pubmed]
PHST- 2022/03/24 06:00 [medline]
PHST- 2022/01/10 00:00 [pmc-release]
AID - 10.1186/s13287-021-02687-x [pii]
AID - 2687 [pii]
AID - 10.1186/s13287-021-02687-x [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2022 Jan 10;13(1):13. doi: 10.1186/s13287-021-02687-x.