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What’s New in Regenerative Medicine: Split up of the Mesenchymal Stem Cell Family Promises New Hope for Cardiovascular Repair

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Abstract

Coronary artery disease (CAD) is exceedingly prevalent and requires care optimization. Regenerative medicine holds promise to improve the clinical outcome of CAD patients. Current approach consists in subsidizing the infarcted heart with boluses of autologous stem cells from the bone marrow. Moreover, mesenchymal stem cells (MSCs) are in the focus of intense research owing to an apparent superiority in plasticity and regenerative capacity compared with hematopoietic stem cells. In this review, we report recent findings indicating the presence, within the heterogeneous MSC population, of perivascular stem cells expressing typical pericyte markers. Moreover, we focus on recent research showing the presence of similar cells in the adventitia of large vessels. These discoveries were fundamental to shape a roadmap toward clinical application in patients with myocardial ischemia. Adventitial stem cells are ideal candidates for promotion of cardiac repair owing to their ease of accessibility and expandability and potent vasculogenic activity.

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Abbreviations

aMI:

Acute myocardial infarction

ATMP:

Advanced therapy medicinal product

ANP:

Atrial natriuretic peptide

BM:

Bone marrow

BMP-2:

Bone morphogenetic protein 2

CO:

Cardiac output

CPCs:

Cardiac progenitor cells

CSCs:

Cardiac stem cells

cTnT:

Cardiac troponin

CABG:

Coronary artery bypass graft

CAD:

Coronary artery disease

CLI:

Critical limb ischemia

FA-MSCs:

Foetal aorta-derived mesenchymal stem cells

EGM2:

Endothelial growth medium

EMEA:

European Medicine Agency

HF:

Heart failure

HGF:

Hepatocyte growth factor

hMSCs:

Human MSCs

HTA:

Human Tissue Authority

IGF-1:

Insulin-like growth factor 1

sLex:

Lewisx

LVEF:

Left ventricular ejection fraction

MSCs:

Mesenchymal stem cells

MeCP2:

Methyl-CpG-binding protein 2

miR-132:

microRNA-132

(β-MHC):

β-myosin heavy chain

MHRA:

Medicine and Healthcare products Regulatory Agency

NHSBT:

National Health System Blood and Transplant

Dll4:

Notch delta-like 4 ligand

PB:

Peripheral blood

PDGF-BB:

Platelet-derived growth factor-BB

PODXL:

Podocalyxin-like protein 1

PSGL-1:

P-selectin glycoprotein ligand 1

RasGAP:

Ras-GTPase activating protein

SOP:

Standard operating protocol

SDF-1:

Stromal cell-derived factor-1

TGFβ1 :

Transforming growth factor β1

VEGF:

Vascular endothelial growth factor

vWF:

von Willerbrand Factor

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Authors and Affiliations

  1. Multimedica IRCCS, Milan, Italy

    Rosa Vono & Gaia Spinetti

  2. Experimental Cardiovascular Medicine, Regenerative Medicine Section, Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Level 7, Bristol Royal Infirmary, Upper Maudlin Street, Bristol, BS2 8HW, UK

    Miriam Gubernator & Paolo Madeddu

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  1. Rosa Vono
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  2. Gaia Spinetti
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  3. Miriam Gubernator
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  4. Paolo Madeddu
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Correspondence to Paolo Madeddu.

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Vono, R., Spinetti, G., Gubernator, M. et al. What’s New in Regenerative Medicine: Split up of the Mesenchymal Stem Cell Family Promises New Hope for Cardiovascular Repair. J. of Cardiovasc. Trans. Res. 5, 689–699 (2012). https://doi.org/10.1007/s12265-012-9395-2

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