Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction

Abstract

Although clinical trials of autologous whole bone marrow for cardiac repair demonstrate promising results, many practical and mechanistic issues regarding this therapy remain highly controversial. Here, we report the results of a randomized study of bone-marrow-derived mesenchymal stem cells, administered to pigs, which offer several new insights regarding cellular cardiomyoplasty. First, cells were safely injected by using a percutaneous-injection catheter 3 d after myocardial infarction. Second, cellular transplantation resulted in long-term engraftment, profound reduction in scar formation, and near-normalization of cardiac function. Third, transplanted cells were preprepared from an allogeneic donor and were not rejected, a major practical advance for widespread application of this therapy. Together, these findings demonstrate that the direct injection of cellular grafts into damaged myocardium is safe and effective in the periinfarct period. The direct delivery of cells to necrotic myocardium offers a valuable alternative to intracoronary cell injections, and the use of allogeneic mesenchymal stem cells provides a valuable strategy for cardiac regenerative therapy that avoids the need for preparing autologous cells from the recipient.

Umbilical cord blood banking: an update

“…These cell types can become an important area to study in medicine allowing for potentially new treatment options for additional diseases or conditions [45] including brain injury [46][47][48], strokes [47,[49][50][51]], Parkinson's [52], Alzheimer's [50,53], Huntington's [54] and amyotrophic lateral sclerosis [50,55]. Other diseases in early stages of investigation include liver disorders [56], diabetes [57,58], and myocardial infarction [49,59]. Therapeutic targets for stem cells from cord blood include orthopedic applications for cartilage repair, spinal fusion and regenerative medicine [27,44,60,61].…”

Bones of contention: Marrow-derived cells in myocardial regeneration

“…My second point has to do with broadening the scope of this debate beyond just bone marrow, which I feel justified in doing since you invoked recent studies on reprogramming of somatic cells. My lab as well as many other well respected research groups have used selected c-kit+ cell populations derived from bone marrow as well as from other tissues that generate cells populations expressing various cardiogenic markers including those of cardiomyocytes following adoptive transfer to cardiomyopathically injured recipients [8][9][10][11][12]. While the process may be relatively inefficient at present, there is every reason to expect that the remarkable salutary effects mediated by adoptive transfer of stem cells in experimental animal models will readily be applied to translational therapy once underlying mechanisms are more fully understood.…”

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

“…Regenerative medicine has been developed in recent years, such as mesenchymal stem cell (MSC) transplantation to repair myocardial infarction (MI) and restore heart function in both animal experiments1, 2, 3, 4 and patients 5, 6, 7, 8, 9, 10. There is mounting evidence that MSCs help repair or regenerate damaged tissues, primarily by means of secreting paracrine factors,11 including antiapoptotic factors,12 proangiogenic factors,13 and exosomes,14 rather than via the differentiation into cardiomyocytes 15, 16, 17…”