Bone Marrow Therapies for Chronic Heart Disease

Abstract

Chronic heart failure is a leading cause of death. The demand for new therapies and the potential regenerative capacity of bone marrow-derived cells has led to numerous clinical trials. We critically discuss current knowledge of the biology and clinical application of bone marrow cells. It appears unlikely that bone marrow cells can develop into functional cardiomyocyte after infusion but may have favorable paracrine effects. Most, but not all, clinical trials report a modest short-but not long-term benefit of infusing bone marrow-derived cells. Effect size appears to correlate with stringency of study-design: the most stringent trials report the smallest effectsizes. We conclude there may be short-but not substantial long-term benefit of infusing bone marrow-derived cells into persons with chronic heart failure and any benefit observed is unlikely to result from trans-differentiation of bone marrow-derived cells into functioning cardiomyocytes. STEM CELLS 2015;33:3212-3227 SIGNIFICANCE STATEMENTThere is considerable controversy whether hematopoietic cell transplants (often incorrectlytermed haematopoietic stem cell transplants) are effective therapy of heart disease in humans. Few publications have reviewed this topic from a stem cell biologists' point of view. In this paper we focused on biology and then critically discuss results of clinical trials.

Poly(Lactide-Co-Glycolide)-Monomethoxy-Poly-(Polyethylene Glycol) Nanoparticles Loaded with Melatonin Protect Adipose-Derived Stem Cells Transplanted in Infarcted Heart Tissue

“…Although medication and operation therapy have decreased mortality associated with myocardial infarction, the infarcted cardiomyocytes cannot regenerate and thus impair cardiac function . Stem cell transplantation provides a potential therapeutic approach to the repair and regeneration of damaged vascular and cardiac tissue after myocardial infarction as it has multilineage differentiation potential and exerts paracrine effects . However, transplanted stem cells in ischemic heart tissue are subjected to apoptosis and necrosis due to the oxidative and inflammatory microenvironment of infarcted areas, which severely restricts the therapeutic efficiency of stem cell transplantation .…”

Biohybrid cochlear implants in human neurosensory restoration

“…Due to their capacity to exert neuroprotection, immunomodulation, neurorestoration, and neurogenesis, autologous BM-MNC were transplanted into patients with cerebral palsy and led to a reduction in disability and to an improvement in the quality of life [ 32 ]. In addition, a short-term benefit of infusing bone marrow-derived cells into patients with chronic heart failure has been observed, and this effect seems to be related to the secretome of these cells [ 33 ]. Thus, BM-MNC have been widely used in human studies as an immune modulator and source of protective growth factors.…”

Key Success Factors for Regenerative Medicine in Acquired Heart Diseases

“…A cell-to-cell communication of CD34+ cells with cardiac myocytes by nanotubes might also contribute to their acquisition of a cardiomyogenic phenotype [141]. In addition, the hypoxic environment of the infarct zone increases vascular endothelial growth factor (VGEF) expression by transplanted cells, which may accelerate the proliferation of endothelial cells and α-SM actin-positive cells (reviewed in [142]).…”