Challenges in identifying the best source of stem cells for cardiac regeneration therapy

Abstract

The overall clinical cardiac regeneration experience suggests that stem cell therapy can be safely performed, but it also underlines the need for reproducible results for their effective use in a real-world scenario. One of the significant challenges is the identification and selection of the best suited stem cell type for regeneration therapy. Bone marrow mononuclear cells, bone marrow-derived mesenchymal stem cells, resident or endogenous cardiac stem cells, endothelial progenitor cells and induced pluripotent stem cells are some of the stem cell types which have been extensively tested for their ability to regenerate the lost myocardium. While most of these cell types are being evaluated in clinical trials for their safety and efficacy, results show significant heterogeneity in terms of efficacy. The enthusiasm surrounding regenerative medicine in the heart has been dampened by the reports of poor survival, proliferation, engraftment, and differentiation of the transplanted cells. Therefore, the primary challenge is to create clearcut evidence on what actually drives the improvement of cardiac function after the administration of stem cells. In this review, we provide an overview of different types of stem cells currently being considered for cardiac regeneration and discuss why associated factors such as practicality and difficulty in cell collection should also be considered when selecting the stem cells for transplantation. Next, we discuss how the experimental variables (type of disease, marker-based selection and use of different isolation techniques) can influence the study outcome. Finally, we provide an outline of the molecular and genetic approaches to increase the functional ability of stem cells before and after transplantation.

Unique Features of Cortical Bone Stem Cells Associated With Repair of the Injured Heart

“…The goals of cell therapy for injured hearts include regeneration of new tissue in place of damaged myocardium, 22 salvaging myocytes that are at risk of death 23 or immunomodulation of the inflammatory response after cardiac insult to improve post MI remodeling. 24 Important factors for enhanced regeneration/repair that we explored in this study include the potency/ potential of the transplanted cells, 25 their capacity to survive, 26 migrate and proliferate, 27 engraft and make connections to the existing neighboring myocytes in the ischemic cardiac milieu. We simultaneously investigated stem cell-derived paracrine, autocrine and growth factors that play an important role in salvaging the existing myocytes and restrict infarct expansion to improve cardiac function.…”

Heart-on-a-chip based on stem cell biology

“…Pluripotent properties of ESCs (derived from the inner cell mass of the blastocyststage embryo) and iPSCs (generated from fibroblast by retroviral transduction of transcription factors such as Sox2, Nanog, c-Myc, Oct4) enable for their differentiation to many different cell types, including cardiac cells (Shah and Shali, 2009Lee et al, 2013, Dey and Evans, 2011. Adult BM cells are heterogeneous and contain various stem cells such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) (Kucia et al, 2004 Dixit andKatare, 2015). The differentiation of these cells is stimulated by biochemical factors, extracellular matrix (ECM) or physical (mechanical, optical, electrical) causes.…”

Cardiac Regenerative Medicine: The Potential of a New Generation of Stem Cells

“…Therefore, combination therapies involving several cell types should be taken into consideration as these might induce synergistic and complementary effects on cardiac regeneration by combining different therapeutic mechanisms at a time. Also, depending on different cardiac pathologies, such as acute MI and chronic ischemic cardiomyopathy, the combination of different cell types might be required to obtain efficient outcomes [50,58], especially because ischemic heart disease does not only affect muscular structure and function but also nervous, vascular and extracellular matrix structures. CCs and 3D-MTs have recently emerged as combinatorial tools to mimic the physiological microenvironment of the target organ [51, 56].…”