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Wharton’s jelly mesenchymal stem cells transplantation for critical limb ischemia in patients with type 2 diabetes mellitus: a preliminary report of phase I clinical trial

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Abstract

Peripheral artery disease (PAD) affects more than 230 million people worldwide, with approximately 11% of patients presenting with advanced-stage PAD or critical limb ischemia (CLI). To avoid or delay amputation, particularly in no-option CLI patients with infeasible or ineffective revascularization, new treatment strategies such as regenerative therapies should be developed. Mesenchymal stem cells (MSCs) are the most popular cell source in regenerative therapies. They possess significant characteristics such as angiogenic, anti-inflammatory, and immunomodulatory activities, which encourage their application in different diseases. This phase I clinical trial reports the safety, feasibility, and probable efficacy of the intramuscular administration of allogeneic Wharton’s jelly-derived MSCs (WJ-MSCs) in type 2 diabetes patients with CLI. Out of six screened patients with CLI, five patients were administered WJ-MSCs into the gastrocnemius, soleus, and the proximal part of the tibialis anterior muscles of the ischemic lower limb. The safety of WJ-MSCs injection was considered a primary outcome. Secondary endpoints included wound healing, the presence of pulse at the disease site, the absence of amputation, and improvement in visual analogue scale (VAS), pain-free walking time, and foot and ankle disability index (FADI). No patient experienced adverse events and foot or even toe amputation during the 6-month follow-up. Six months after the intervention, there were a significantly lower VAS score and significantly higher pain-free walking time and FADI score than the baseline, but no statistically significant difference was seen between other time points. In conclusion, allogeneic WJ-MSC transplantation in patients with CLI seems to be safe and effective.

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Availability of data and material

All data are available by corresponding author.

Abbreviations

AE:

Adverse event

CLI:

Critical limb ischemia

FADI:

Foot and ankle disability index

NO-CLI:

No-option CLI

VAS:

Visual analogue scale

WJ-MSC:

Wharton’s jelly-derived mesenchymal stem cell

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Acknowledgements

The authors kindly thank the Regenerative Medicine, Organ Procurement and Transplantation Multi-Disciplinary Center based on Razi Hospital, Rasht for helping and supporting this study.

Funding

This study was supported by a grant from Guilan University of Medical Sciences (Trial registration: IRCT, 20211021052828N2. Registered May 15, 2022).

Author information

Authors and Affiliations

  1. Department of General Surgery, School of Medicine Road Trauma Research Center, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran

    Mohammad Taghi Ashoobi, Hossein Hemmati & Saeed Yousefi

  2. Razi Clinical Research Development Unit, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran

    Hossein Hemmati & Mohaya Farzin

  3. Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Hamid Reza Aghayan

  4. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

    Zeinab Zarei-Behjani

  5. School of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran

    Samaneh Keshavarz & Elham Vojoudi

  6. Biotechnology Research Center, International Campus, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Hamideh Babaloo

  7. Department of Biostatistics, School of Health, Guilan University of Medical Sciences, Rasht, Iran

    Saman Maroufizadeh

Authors
  1. Mohammad Taghi Ashoobi
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  2. Hossein Hemmati
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Contributions

MTA: conceptualization, investigation of the study, data analysis, writing the initial draft, verification of the final version of manuscript. HH: conceptualization, investigation of the study, verification of the final version of manuscript. HRA: conceptualization, investigation of the study, verification of the final version of manuscript. ZZB: conceptualization, verification of the final version of manuscript. SK: conceptualization, verification of the final version of manuscript. HB: conceptualization, verification of the final version of manuscript. SM: data analysis, verification of the final version of manuscript. SE: investigation of the study, writing the initial draft, verification of the final version of manuscript. MF: helping to gather data, verification of the final version of manuscript. EV: conceptualization, investigation of the study, data analysis, writing the initial draft, verification of the final version of manuscript, submitting the manuscript.

Corresponding authors

Correspondence to Hossein Hemmati or Elham Vojoudi.

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Ethics approval and consent to participate

This study complied with the ethical standards of the Guilan University of Medical Sciences with this number: IR.GUMS.REC.1401.015 (IRCT NO. IRCT20211021052828N2). Written informed consent was obtained from all participants.

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Not applicable.

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The authors declare no competing interests.

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Ashoobi, M.T., Hemmati, H., Aghayan, H.R. et al. Wharton’s jelly mesenchymal stem cells transplantation for critical limb ischemia in patients with type 2 diabetes mellitus: a preliminary report of phase I clinical trial. Cell Tissue Res 395, 211–220 (2024). https://doi.org/10.1007/s00441-023-03854-7

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