Key Success Factors for Regenerative Medicine in Acquired Heart Diseases

Abstract

Stem cell therapy offers a breakthrough opportunity for the improvement of ischemic heart diseases. Numerous clinical trials and meta-analyses appear to confirm its positive but variable effects on heart function. Whereas these trials widely differed in design, cell type, source, and doses reinjected, cell injection route and timing, and type of cardiac disease, crucial key factors that may favour the success of cell therapy emerge from the review of their data. Various types of cell have been delivered. Injection of myoblasts does not improve heart function and is often responsible for severe ventricular arrythmia occurrence. Using bone marrow mononuclear cells is a misconception, as they are not stem cells but mainly a mix of various cells of hematopoietic lineages and stromal cells, only containing very low numbers of cells that have stem cell-like features; this likely explain the neutral results or at best the modest improvement in heart function reported after their injection. The true existence of cardiac stem cells now appears to be highly discredited, at least in adults. Mesenchymal stem cells do not repair the damaged myocardial tissue but attenuate post-infarction remodelling and contribute to revascularization of the hibernated zone surrounding the scar. CD34 + stem cells-likely issued from pluripotent very small embryonic-like (VSEL) stem cells-emerge as the most convincing cell type, inducing structural and functional repair of the ischemic myocardial area, providing they can be delivered in large amounts via intra-myocardial rather than intra-coronary injection, and preferentially after myocardial infarct rather than chronic heart failure.

Mesenchymal Stromal Cells from Different Parts of Umbilical Cord: Approach to Comparison & Characteristics

“…Research is also being conducted on WJ-MSC in neurological diseases in young patients with cerebral palsy, autism, traumatic brain damage and hypoxic-ischemic encephalopathy. WJ-MSCs were also used in hematology (aplastic anemia, graft-versus host disease (GVHD)), cardiology (chronic coronary disease, heart failure), immunology (systemic lupus erythematosus), musculoskeletal diseases (Duchene and Becker disease) and others (including rare diseases) [99][100][101][102][103] These clinical trials do not exceed phase II. Most of them have demonstrated safety in clinical use, but minority treated efficacy as a main endpoint.…”

Transplantation of CD34+ cells for myocardial ischemia

“…Indeed, a reduction in post-AMI major adverse cardiovascular events and an improvement in left ventricular function at 6 mo after cell injection were observed[ 39 ]. We noticed that therapeutic results of CD34+ cell implantation were dose-dependent[ 6 , 38 - 41 ]. Greater improvement was associated with higher doses with a threshold dose of over 10 million cells, particularly in the setting of myocardial infarction[ 40 , 41 ].…”

“…CD34+ cells are multipotent hematopoietic stem cells also known as endothelial progenitor cells and are useful in regenerative medicine for treating ischemic injuries[ 5 ]. These cells are easily mobilized from the bone marrow into peripheral circulation and characterized by their ability to promote neoangiogenesis and cardiomyocyte regeneration[ 6 ]. Previous published trials have reported the effectiveness of CD34+ cell implantation for treating ischemic vascular disease like ischemic stroke, peripheral limb ischemia and MI[ 7 , 8 ].…”

Endogenous Mobilization of Mesenchymal Stromal Cells: A Pathway for Interorgan Communication?

“…Culture-expanded MSCs consist of a heterogeneous population of cells exhibiting various phenotypes and functional properties, and the extent of these properties depends on the tissue, donor, and species of origin, isolation technique, and culturing protocols ( Ankrum et al, 2014 ). Such variations are known to limit the potential of MSCs for clinical translation, and strategies to enhance engraftment are needed ( Hou et al, 2005 ; Hénon, 2020 ).…”