Article

Stem Cell Reviews and Reports

, Volume 9, Issue 3, pp 281-302

First online:

Optimization of the Cardiovascular Therapeutic Properties of Mesenchymal Stromal/Stem Cells–Taking the Next Step

  • James D. RichardsonAffiliated withCardiovascular Research Centre, Royal Adelaide Hospital and Department of Medicine, University of Adelaide
  • , Adam J. NelsonAffiliated withCardiovascular Research Centre, Royal Adelaide Hospital and Department of Medicine, University of Adelaide
  • , Andrew C. W. ZannettinoAffiliated withDepartment of Haematology, SA Pathology and Centre for Stem Cell Research, Robinson Institute, Discipline of Medicine, University of Adelaide
  • , Stan GronthosAffiliated withDepartment of Haematology, SA Pathology and Centre for Stem Cell Research, Robinson Institute, Discipline of Medicine, University of Adelaide
  • , Stephen G. WorthleyAffiliated withCardiovascular Research Centre, Royal Adelaide Hospital and Department of Medicine, University of Adelaide
  • , Peter J. PsaltisAffiliated withCardiovascular Research Centre, Royal Adelaide Hospital and Department of Medicine, University of AdelaideDivision of Cardiovascular Diseases, Mayo Clinic Email author 

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Abstract

Despite current treatment options, cardiac failure is associated with significant morbidity and mortality highlighting a compelling clinical need for novel therapeutic approaches. Based on promising pre-clinical data, stem cell therapy has been suggested as a possible therapeutic strategy. Of the candidate cell types evaluated, mesenchymal stromal/stem cells (MSCs) have been widely evaluated due to their ease of isolation and ex vivo expansion, potential allogeneic utility and capacity to promote neo-angiogenesis and endogenous cardiac repair. However, the clinical application of MSCs for mainstream cardiovascular use is currently hindered by several important limitations, including suboptimal retention and engraftment and restricted capacity for bona fide cardiomyocyte regeneration. Consequently, this has prompted intense efforts to advance the therapeutic properties of MSCs for cardiovascular disease. In this review, we consider the scope of benefit from traditional plastic adherence-isolated MSCs and the lessons learned from their conventional use in preclinical and clinical studies. Focus is then given to the evolving strategies aimed at optimizing MSC therapy, including discussion of cell-targeted techniques that encompass the preparation, pre-conditioning and manipulation of these cells ex vivo, methods to improve their delivery to the heart and innovative substrate-directed strategies to support their interaction with the host myocardium.

Keywords

Cardiomyopathy Ischemic heart disease Limitations Mesenchymal stem cells Mesenchymal precursor cells Myocardial infarction Optimization Paracrine Pre-conditioning Tissue engineering