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Cell Therapy in Peripheral Artery Disease

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PanVascular Medicine

Abstract

Cell therapy has been proposed as an alternative strategy in patients with critical limb ischemia who are not eligible for endovascular or surgical revascularization. Several preclinical and clinical studies suggest that delivery of stem cells with regenerative potential and paracrine ability can improve blood circulation and tissue perfusion and thus prevent amputation via the induction of capillary or collateral growth in a process called “therapeutic angiogenesis.” Many cell types have been tested, but results of most clinical trials to date rely on the use of adult autologous bone marrow–derived mononuclear cells or cultured peripheral blood–derived proangiogenic mononuclear cells, all typically delivered unaltered in their native state. Of increased interest are mesenchymal stem cells with a capability for multipotent differentiation, cytoprotection, and damaged tissue restoration. Although the meta-analyses of randomized clinical trials demonstrate a positive benefit-to-risk ratio of cell-based therapy, its promising potential needs to be confirmed by larger randomized, placebo-controlled trials. Despite the progress in basic and clinical research and the development of new technologies, there are open issues that need to be solved, such as the optimal therapeutic cell types, methods of cell harvesting, route of delivery, and enhancement of cell reparative function. This chapter provides a summary of evidence, highlights current standing, and appraises the future perspectives of cell therapy in patients with peripheral artery disease.

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Abbreviations

Angiogenesis:

The sprouting of new capillaries from preexisting vessels; one of the mechanisms of neovascularization.

Arteriogenesis:

Remodeling of newly formed or preexisting vascular channels into larger and well-muscularized arterioles and collateral vessels; one of the mechanisms of neovascularization.

Endothelial progenitor cells:

Subpopulation of the mononuclear fraction of bone marrow or peripheral blood cells with the ability to generate cells with an endothelial phenotype.

Mesenchymal stem cells:

Nonhematopoetic cells present in bone marrow, adipose tissue, and other tissue sources involved in regenerative processes with extensive proliferative and secretory capacity and multilineage potential.

No-option critical limb ischemia:

Advanced critical limb ischemia with failed or impossible endovascular or surgical revascularization.

Stem cells:

Nonmature, nondifferentiated tissue precursors with high potential for self-renewal and the ability to differentiate into different cells lines based on stimuli from the surrounding environment.

ABI:

Ankle brachial index

AFS:

Amputation free survival

ANG:

Angiopoetin

BMA:

Bone marrow aspirate concentrate

BMCs:

Bone marrow cells

BM-MNCs:

Bone marrow mononuclear cells

BM-MSCs:

Bone marrow mesenchymal cells

CLI:

Critical limb ischemia

DSA:

Digital subtraction angiography

EPCs:

Endothelial progenitor cells

FGF:

Fibroblast growth factor

G-CSF:

Granulocyte colony-stimulating factor

HIF-1:

Hypoxia-inducible factor 1

IL:

Interleukin

MRI:

Magnetic resonance imaging

MSCs:

Mesenchymal stem cells

NO-CLI:

No-option critical limb ischemia

PAD:

Peripheral artery disease

PDGF:

Platelet-derived growth factor

PET:

Positron emission tomography

RCT:

Randomized controlled trial

SDF-1:

Stromal cell-derived factor 1

SPECT:

Single-photon emission computed tomography

tcpO2 :

Transcutaneous oxygen pressure

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Cardiology and Angiology, National Institute of Heart and Vascular Disease, Pod Krasnou horkou 1, 833 48, Bratislava, Slovakia

    Juraj Madaric

  2. Department of Diagnostic and Interventional Radiology, National Institute of Heart and Vascular Disease, Bratislava, Slovakia

    Andrej Klepanec

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  1. Juraj Madaric
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  2. Andrej Klepanec
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Correspondence to Juraj Madaric .

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  1. Division of Cardiovascular Disease Department of Internal Medicine, Health Care Center Bitterfeld, Bitterfeld-Wolfen, Germany

    Peter Lanzer

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Madaric, J., Klepanec, A. (2015). Cell Therapy in Peripheral Artery Disease. In: Lanzer, P. (eds) PanVascular Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37078-6_193

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  • DOI: https://doi.org/10.1007/978-3-642-37078-6_193

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