Mesenchymal stem cells for cardiac repair: are the actors ready for the clinical scenario?

Abstract

For years, sufficient progress has been made in treating heart failure following myocardial infarction; however, the social and economic burdens and the costs to world health systems remain high. Moreover, treatment advances have not resolved the underlying problem of functional heart tissue loss. In this field of research, for years we have actively explored innovative biotherapies for cardiac repair. Here, we present a general, critical overview of our experience in using mesenchymal stem cells, derived from cardiac adipose tissue and umbilical cord blood, in a variety of cell therapy and tissue engineering approaches. We also include the latest advances and future challenges, including good manufacturing practice and regulatory issues. Finally, we evaluate whether recent approaches hold potential for reliable translation to clinical trials.

Determination of HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 allele and haplotype frequencies in heart failure patients

“…Roura et al As the field of cell-based therapy evolves, it has become evident that various cell typesmesenchymal stem cells (MSCs) being the prototypehave sufficient ability to evade and/or suppress the immune system to the extent that they may be used as allografts without requiring concomitant immunosuppression. 25,26 Thus, alternative cell sources are being examined, including pluripotent stem cells (iPS). Paracrine signalling is consistent with findings in which a low number of retained or seeded cells could promote restorative effects, such as forming vessels to protect resident cardiomyocytes from apoptosis, and mobilize host stem or progenitor cells to potentiate both vascularization and cardiomyogenesis.…”

“…Paracrine signalling is consistent with findings in which a low number of retained or seeded cells could promote restorative effects, such as forming vessels to protect resident cardiomyocytes from apoptosis, and mobilize host stem or progenitor cells to potentiate both vascularization and cardiomyogenesis. 25,26 Thus, alternative cell sources are being examined, including pluripotent stem cells (iPS). The iPS cells are in the preclinical stage, can be generated after inducing the expression of transcription factors associated with pluripotency, and exhibit unlimited self-renewal and differentiation to many cell lineage types.…”

Human dental pulp stem cells regulate allogeneic NK cells’ function via induction of anti‐inflammatory purinergic signalling in activated NK cells

“…[1][2][3][4] By virtue of their low immunogenicity and immune-regulating function, mesenchymal stem cells (MSCs) might be applied to modulate the immune responses in immune diseases, for example, graft-vs-host disease (GVHD) or autoimmune disease, 5,6 and regenerating damaged tissues, such as cardiac healing after myocardial infarction. 7 Since bone marrow mesenchymal stem cells (BMMSCs) had low proliferative potential and were difficult to isolate from bone marrow through painful invasions, 8 better sources of MSCs were needed for cell-based clinical treatment. 9 MSCs from dental tissues had self-renewal capacity and multi-differentiation potential and represented an easily available alternative source of cells.…”

Generation of functional human adipose tissue in mice from primed progenitor cells

“…In some examples, AT is used for volume restoration after surgery for breast cancer (7), for soft tissue reconstruction in acquired or congenital malformations (8,9) and to fill defects such as cranial fractures or fistulas in cranial neurosurgery (10)(11)(12). In the context of regeneration, mesenchymal cells from adipose tissue have been used for numerous purposes including cardiomyocyte (13), bowel (14), tendon and bone regeneration (15). In the setting of volume restoration, reabsorption and necrosis of grafted fat are a frequent complication (16,17), resulting in the need for repeated surgical procedures in > 25% of cases.…”