Thymosin β4-enhancing therapeutic efficacy of human adipose-derived stem cells in mouse ischemic hindlimb model

Jong Ho Kim, I. Rang Lim, Chi Yeon Park, Hyung Joon Joo, Ji Min Noh, Seung Cheol Choi, Soon Jun Hong, Do Sun Lim

Research output: Contribution to journalArticle

Abstract

Thymosin β4 (Tβ4) 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 Tβ4 and human adipose-derived stem cells (hASCs) in a mouse ischemic hindlimb model were investigated. We observed that exogenous treatment with Tβ4 enhanced endogenous TMSB4X mRNA expression and promoted morphological changes (increased cell length) in hASCs. Interestingly, Tβ4 induced the active state of hASCs by up-regulating intracellular signaling pathways including the PI3K/AKT/mTOR and MAPK/ERK pathways. Treatment with Tβ4 significantly increased cell migration and sprouting from microbeads. Moreover, additional treatment with Tβ4 promoted the endothelial differentiation potential of hASCs by up-regulating various angiogenic genes. To evaluate the in vivo effects of the Tβ4-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 Tβ4 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 Tβ4 could be effective in enhancing endothelial differentiation and vascularization for treating hindlimb ischemia.

Original languageEnglish
Article number2166
JournalInternational journal of molecular sciences
Volume21
Issue number6
DOIs
Publication statusPublished - 2020 Mar 2

Keywords

  • Adipose-derived stem cells
  • Endothelial Differentiation
  • Hindlimb ischemia
  • Thymosin β4
  • Vascularization

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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