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Cardiac Stem Cells: A Plethora of Potential Therapies for Myocardial Regeneration Within Reach

  • Enrique Gallego-Colon
  • Eduardo Oliver
Chapter

Abstract

The limited regenerative capacity of the adult heart hinders cardiac regeneration and still remains an unsolved therapeutic target. In the last decade, the development of cell-based approaches for the treatment of myocardial infarction has made substantial progress. The use of cardiac stem cells (CSC) represents a promising therapeutic tool upon massive loss of cardiac tissue such as after myocardial infarction. Different putative CSC populations, with self-renewing capacity and potential to differentiate into cardiomyocytes, smooth muscle, or endothelial cells, are under evaluation. Preclinical studies have discovered various pools of putative CSC including c-kit cardiac progenitor cells (CPCs), epicardium-derived cells (EPDC), Sca-1, cardiac side population (cSP), islet-1 CPC, cardiosphere-derived cells (CDCs), cardiac colony-forming unit fibroblast (cCFU-F), cardiac atrial appendage stem cells (CASCs), bone marrow-derived CSC (BMdCSC), and modified embryonic or induced pluripotent stem cells. Preclinical studies provided encouraging results on the ability of CSC to restore cardiac contractility, regional and global function, myocyte survival, and the remodeling process. Although CSC therapy is safe and feasible in the clinics, heterogeneous outcomes have cast doubts on CSC efficacy to promote cardiac regeneration. Overall, the poor engraftment of transplanted CSC highlights the possibility that the observed beneficial effects may be attributed to the release of paracrine factors rather than CSC ability to reconstitute functional well-differentiated myocardium. Unfortunately, controversy remains around the benefit of CSC therapy, and big challenges such as ideal dose, identification and selection of the best CSC type, delivery system, and concomitant treatments must be addressed. The success of CSC regenerative therapies implies more basic research, and further clinical trials are needed before to reach the clinical practice and fulfill the long-lasting goal of cardiac regeneration.

Keywords

Cardiac regeneration Myocardial infarction Ischemic disease Cardiac stem cells Cardiac progenitor cell Cardiac function Clinical trials Preclinical studies 

Abbreviations

5-aza

5′-Azacytidine

bFGF

Basic fibroblast growth factor

BM

Bone marrow

BMdC

Bone marrow-derived cells

CABG

Coronary artery bypass surgery

CASCs

Cardiac atrial appendage stem cells

cCFU-F

Cardiac colony-forming unit fibroblast

CDCs

Cardiosphere-derived cells

CPCs

Cardiac progenitor cells

CSC

Cardiac stem cell

cSP

Cardiac side population

EF

Ejection fraction

EMT

Epithelial-to-mesenchymal transition

EPDC

Epicardium-derived cells

ESC

Embryonic stem cells

GFP

Green fluorescent protein

HF

Heart failure

IGF-1

Insulin growth factor 1

IHD

Ischemic heart disease

iPSC

Induced pluripotent stem cells

MI

Myocardial infarction

MRI

Magnetic resonance imaging

MSC

Mesenchymal stem cells

Sca-1

Stem cell antigen-1

Notes

Acknowledgments

E.J.G-C wants to acknowledge the EU FP7-Marie Curie-ITN fellows and lecturers for the scientific input over the years when E.J.G-C was a Marie Curie Fellow. During the preparation of this chapter, E.O. was recipient of a CNIC-IPP Research Fellowship funded by the FP7-PEOPLE-2012-COFUND - Marie Curie Action (600396 / 17214-2016), and is currently supported by the 'Talent Attraction program' of Comunidad de Madrid (2017-T1/BMD-5185). The CNIC is supported by the Ministerio de Economía, Industria y Competitividad (MEIC) and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).

Disclosures

E.J.G-C. and E.O. declare no competing financial interests or conflict of interest.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of BiochemistryMedical University of Silesia, School of Medicine in KatowiceKatowicePoland
  2. 2.Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)MadridSpain

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