Abstract

Previously, we reported the angio-vasculogenic properties of human stromal vascular fraction (SVF) and adipose tissue-derived mesenchymal stem cells (ASCs). In this study, we investigated whether the combination of ASCs and SVF cells exhibited synergistic angiogenic properties. We conducted quantitative (q)RT-PCR, Matrigel plug, tube formation assays, and in vivo therapeutic assays using an ischemic hind limb mouse model. Immunohistochemical analysis was also conducted. qRT-PCR results revealed that FGF-2 was highly upregulated in ASCs compared with SVF, while PDGF-b and VEGF-A were highly upregulated in SVF. Conditioned medium from mixed cultures of ASCs and SVF (A+S) cells showed higher Matrigel tube formation and endothelial cell proliferation in vitro. A+S cell transplantation into ischemic mouse hind limbs strongly prevented limb loss and augmented blood perfusion compared with SVF cell transplantation. Transplanted A+S cells also showed high capillary density, cell proliferation, angiogenic cytokines, and anti-apoptotic potential in vivo compared with transplanted SVF. Our data indicate that A+S cell transplantation results in synergistic angiogenic therapeutic effects. Accordingly, A+S cell injection could be an alternative therapeutic strategy for treating ischemic diseases.

Highlights

  • Published: 24 December 2021Since its inception, stem cell therapy has emerged as an attractive therapeutic option for the treatment of damaged organs

  • stromal vascular fraction (SVF) cells sized that theselevels cells could exhibit and synergistic angiogenic potential when mixed transexpressed higher of Platelet Derived Growth Factor (PDGF)-b compared to adipose-derived mesenchymal stem cells (MSCs) (ASCs)

  • The results revealed that the Culture media (CM) of A+S cells induced significantly higher tube lengths and branching points than the CM of SVF cells (Figure 2A,B)

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Summary

Introduction

Stem cell therapy has emerged as an attractive therapeutic option for the treatment of damaged organs. Dual stem cell therapy, such as early/late effects in promoting neovascularization [10,11]. Dual stem cell therapy, such as early/late endothelial progenitor cells cardiomyocytesderived derivedfrom frominduced induced pluripotent pluripotent stem stem cells, endothelial progenitor cells or or cardiomyocytes cells, synergistically improves cardiac function and vascular regeneration in the isalso synergistically improves cardiac function and vascular regeneration in the ischemic chemic heart by stem cell homing and the prolonged secretion of paracrine factors [12,13]. Stem cell therapy has to enhance the therapeutic potential in damaged [14].heart. In been limited by marginal or transitional in ischemic heart diseasestherapeutic [15,16] In this this study, we investigated whetherinfluences.

Cell To
Angiogenicproperties properties of of ASCs
3.3.Discussion
SVF Isolation
Cell Culture
Matrigel Plug In Vivo Assay
Matrigel Tube Formation Assay
Scratch Wound Assays
Apoptosis Assay
4.10. Induction of Ischemic Hindlimb Model and Cell Transplantation
4.11. Histological Analysis
4.12. Statistical Analysis
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