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Stem and Somatic Cell Monotherapy for the Treatment of Diabetic Foot Ulcers: Review of Clinical Studies and Mechanisms of Action

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Abstract

Diabetic foot ulcer (DFU) is one of the most severe complications of diabetes mellitus, often resulting in a limb amputation. A cell-based therapy is a highly promising approach for an effective DFU treatment. However, there is no consensus regarding the most effective cell type for DFU treatment. Various cell types contribute to chronic wound healing via different mechanisms. For example, application of keratinocytes can stimulate migration of native keratinocytes from the wound edge, while mesenchymal stem cells can correct limb ischemia. To assess the effectiveness of a certain cell type, it should be administered as a monotherapy without other substances and procedures that have additional therapeutic effects. In the present review, we described therapeutic effects of various cells and provided an overview of clinical studies in which stem and somatic cell-based therapy was administered as a monotherapy. Topical application of somatic cells contributes to DFU healing only, while injection of mesenchymal stem cells and mononuclear cells can break a pathophysiological chain leading from insufficient blood supply to DFU development. At the same time, the systemic use of mesenchymal stem cells carries greater risks. Undoubtedly, cell therapy is a potent tool for the treatment of DFU. However, it is vital to conduct further high-quality clinical research to determine the most effective cell type, dosage and way of administration for DFU treatment.

Graphical abstract

Ischemia, neuropathy and neuro-ischemia are underlying factors of diabetic foot ulcer. Stem and somatic cells monotherapy can improve chronic wound healing via different mechanisms.

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Abbreviations

AD-MSCs:

Adipose tissue-derived mesenchymal stem cells

bFGF:

Basic fibroblast growth factor

BM-MNCs:

Bone marrow-derived mononuclear cells

DFU:

Diabetic foot ulcer

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

EPC:

Endothelial progenitor cells

HGF:

Hepatocyte growth factor

IDF:

International Diabetes Federation

IGF:

Insulin growth factor

Il:

Interleukin

MSCs:

Mesenchymal stem cells

G-CSF:

Granulocyte colony-stimulating factor

MMP:

Matrix metalloproteinase

PB-MNCs:

Peripheral blood mononuclear cells

PDGF:

Platelet-derived growth factor

TGF:

Transforming growth factor

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. A. Tsyb Medical Radiological Research Center - branch of the National Medical Research Radiological Center, Obninsk, Russia

    O. A. Krasilnikova & D. S. Baranovskii

  2. Research and Educational Resource Center for Cellular Technologies, Peoples’ Friendship University of Russia (RUDN University), Moscow, Russia

    D. S. Baranovskii, A. V. Lyundup, A. D. Kaprin & I. D. Klabukov

  3. Department of Regenerative Medicine, National Medical Research Radiological Center, Obninsk, Russia

    P. V. Shegay, A. D. Kaprin & I. D. Klabukov

  4. Obninsk Institute for Nuclear Power Engineering of the National Research Nuclear University MEPhI, Obninsk, Russia

    I. D. Klabukov

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  1. O. A. Krasilnikova
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OK and IK designed the study. DB contributed to the interpretation of the data. OK, IK, and DB drafted the manuscript. AL, PS and AK supervised the study. All authors approved the final version of the manuscript.

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This article belongs to the Topical Collection: Special Issue on Stem Cell Technology and Skin Disorders (Dermatology): from Stem Cell Biology to Clinical Application

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Krasilnikova, O.A., Baranovskii, D.S., Lyundup, A.V. et al. Stem and Somatic Cell Monotherapy for the Treatment of Diabetic Foot Ulcers: Review of Clinical Studies and Mechanisms of Action. Stem Cell Rev and Rep 18, 1974–1985 (2022). https://doi.org/10.1007/s12015-022-10379-z

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