Thymosin beta 4-Enhancing Therapeutic Efficacy of Human Adipose-Derived Stem Cells in Mouse Ischemic Hindlimb Model
- Authors
- Kim, Jong-Ho; Lim, I-Rang; Park, Chi-Yeon; Joo, Hyung Joon; Noh, Ji-Min; Choi, Seung-Cheol; Hong, Soon Jun; Lim, Do-Sun
- Issue Date
- Mar-2020
- Publisher
- Multidisciplinary Digital Publishing Institute (MDPI)
- Keywords
- Thymosin beta 4; Adipose-derived stem cells; Endothelial Differentiation; Vascularization; Hindlimb ischemia
- Citation
- International Journal of Molecular Sciences, v.21, no.6
- Indexed
- SCIE
SCOPUS
- Journal Title
- International Journal of Molecular Sciences
- Volume
- 21
- Number
- 6
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/998
- DOI
- 10.3390/ijms21062166
- ISSN
- 1661-6596
1422-0067
- Abstract
- Thymosin beta 4 (T beta 4) is a G-actin sequestering protein that contributes to diverse cellular activities, such as migration and angiogenesis. In this study, the beneficial effects of combined cell therapy with T beta 4 and human adipose-derived stem cells (hASCs) in a mouse ischemic hindlimb model were investigated. We observed that exogenous treatment with T beta 4 enhanced endogenous TMSB4X mRNA expression and promoted morphological changes (increased cell length) in hASCs. Interestingly, T beta 4 induced the active state of hASCs by up-regulating intracellular signaling pathways including the PI3K/AKT/mTOR and MAPK/ERK pathways. Treatment with T beta 4 significantly increased cell migration and sprouting from microbeads. Moreover, additional treatment with T beta 4 promoted the endothelial differentiation potential of hASCs by up-regulating various angiogenic genes. To evaluate the in vivo effects of the T beta 4-hASCs combination on vessel recruitment, dorsal window chambers were transplanted, and the co-treated mice were found to have a significantly increased number of microvessel branches. Transplantation of hASCs in combination with T beta 4 was found to improve blood flow and attenuate limb or foot loss post-ischemia compared to transplantation with hASCs alone. Taken together, the therapeutic application of hASCs combined with T beta 4 could be effective in enhancing endothelial differentiation and vascularization for treating hindlimb ischemia.
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Collections - 4. Research institute > Metabolic Syndrome Research Center > 1. Journal Articles
- 2. Clinical Science > Department of Cardiology > 1. Journal Articles
- 3. Graduate School > Graduate School > 1. Journal Articles
- 4. Research institute > Cardiovascular Research Institute > 1. Journal Articles
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