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Comparative study of mouse adipose- and bone marrow mesenchymal stem cells in diabetic model with critical limb ischemia

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Abstract

The aim of this research is to compare the capabilities of Adipose tissue mesenchymal stem cells (AT-MSCs) and bone marrow mesenchymal stem cells (BM-MSCs) in the treatment of diabetic male mice with CLI model. Supernatants were collected from C57BL/6 mice isolated AT-MSCs and BM-MSCs, afterward their effects on human umbilical vein endothelial (HUVEC) migration potential were evaluated. Diabetes mellitus type 1 was induced by streptozotocin injection. Diabetic mice with CLI model were divided into three groups and injected with AT-MSCs, BM-MSCs, or PBS then the efficacy of them was assessed. Survival of MSCs was analysed by SRY-specific gene. The conditioned medium of AT-MSCs and BM-MSCs stimulated HUVECs migration and the donor cells were detected till 21 day in two groups. BM-MSCs and AT-MSCs improved significantly functional recovery and ischemia damage. Neovascularization in ischemic muscle was significantly higher in mice treated with AT-MSCs and BM-MSCs and they improved muscle regeneration. In vivo and in vitro findings show that AT-MSCs and BM-MSCs transplantation could be proposed as a promising therapy to promote angiogenesis and muscle regeneration through secretion of proangiogenic factors, cytokines and growth factors in diabetic mice with CLI model wherein blood supply is insufficient and disrupted.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

CLI:

Critical limb ischemia

PAD:

Peripheral arterial disease

MSCs:

Mesenchymal stem cells

AT-MSC:

Adipose tissue mesenchymal stem cell

BM-MSCs:

Bone marrow mesenchymal stem cells

HUVECs:

Humanumbilical vein endothelial cell

MVD:

Microvessel density

DM:

Diabetes mellitus

VEGF:

Vascular endothelial growth factor

STZ:

Streptozotocin

PBS:

Phosphate-buffered saline

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

Fetal bovine serum

IP:

Intraperitoneal

IM:

Intramuscular

H&E:

Hematoxylin and eosin

IHC:

Immunohistochemical

PFA:

Paraformaldehyde

TBS:

Buffered Saline

DAB:

Diaminobenzidine tetrahydrochloride

SD:

Standard deviation

RMANOVA:

Two-way analysis of variance test with repeated measurements

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Acknowledgements

The present study was financially supported by Shahid Sadoughi University of Medical Sciences, Yazd, Iran and Shiraz University of Medical Sciences, Shiraz, Iran. Also, the authors would like to thank the Research Consulting Center of Shiraz University of Medical Sciences (RCC) for their assistance in statistical analysis.

Funding

This work was supported by Shahid Sadoughi University of Medical Sciences Foundation (5984).

Author information

Authors and Affiliations

  1. Department of Molecular Medicine, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Seyedeh-Leili Asadi-Yousefabad

  2. Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

    Pegah Nammian & Vahid Razban

  3. Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Mohammad Hasan Sheikhha

  4. Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Mohammad Hasan Sheikhha

  5. Department of Medical Genetics, School of Medical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

    Seyed Mohammad Bagher Tabei

  6. Maternal-fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Seyed Mohammad Bagher Tabei

  7. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Sajad Daneshi

  8. Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Habib Nikukar

  9. Department of Medical Genetics, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Marzieh Lotfi

  10. Stem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Vahid Razban

Authors
  1. Seyedeh-Leili Asadi-Yousefabad
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  2. Pegah Nammian
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  3. Mohammad Hasan Sheikhha
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  4. Seyed Mohammad Bagher Tabei
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  5. Sajad Daneshi
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  6. Habib Nikukar
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  7. Marzieh Lotfi
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  8. Vahid Razban
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Contributions

SLAY: Conceptualization, Methodology, Investigation, Data curation, Project administration, Writing - original draft. PN: Conceptualization, Methodology, Investigation, Data curation. MS: Supervision, Writing - review & editing, Data curation, Validation, Funding acquisition. SMBT: Supervision, Writing - review & editing, Funding acquisition. SD: Methodology, Investigation, Data curation. HN: Data curation, Validation. ML: Data curation, Validation. VR: Supervision, Writing - review & editing, Data curation, Validation. The authors read and approved the final manuscript.

Corresponding authors

Correspondence to Mohammad Hasan Sheikhha or Vahid Razban.

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Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethics approval and consent to participate

All methods were performed in accordance with the regulations and guidelines approved by the ethics committee of Shahid Sadoughi University of Medical Sciences (IR.SSU.MEDICINE.REC.1397.031).

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Asadi-Yousefabad, SL., Nammian, P., Sheikhha, M.H. et al. Comparative study of mouse adipose- and bone marrow mesenchymal stem cells in diabetic model with critical limb ischemia. Cell Tissue Bank 23, 923–936 (2022). https://doi.org/10.1007/s10561-022-10007-7

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  • DOI: https://doi.org/10.1007/s10561-022-10007-7

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