The Bone Marrow—Cardiac Axis of Myocardial Regeneration

Abstract

Congestive heart failure remains the leading cause of morbidity and mortality in the developed world. Current therapies do not address the underlying pathophysiology of this disease, namely the progressive loss of functional cardiomyocytes. The notion of repairing or regenerating lost myocardium via cell based therapies remains highly appealing. The recent identification of adult stem cells, including both cardiac stem/progenitor cells and bone marrow stem cells, has triggered an explosive interest in utilizing these cells for physiologically relevant cardiomyogenesis. Enthusiasm for cardiac regeneration via cell therapy has further been fueled by the many encouraging reports in both animals and human studies. Further intensive research in basic science and clinical arenas are needed in order to make this next great frontier in cardiovascular regenerative medicine a reality. In this review, we focus on the role of bone marrow derived stem cells and cardiac stem/ progenitor cells in cardiomyocyte homeostasis and myocardial repair and regeneration, as well as provide a brief overview of current clinical trials utilizing cell-based therapeutic approaches in patients with heart disease.Despite advances in the treatment of congestive heart failure (CHF), morbidity and mortality remain inappropriately high 1 This medical epidemic has only continued to escalate, given an overall aging population and the greater number of patients surviving an initial myocardial infarction (MI). The pathophysiology of post-MI heart failure is driven by the loss of cardiomyocytes, either due to acute ischemic necrosis or chronic apoptosis, and the inability of the remaining cardiomyocytes to adequately compensate. As such, the concept of repairing or regenerating lost myocardium via cell based therapies (so termed "cardiomyoplasty") remains highly appealing. Over the past decade, much research has focused upon identifying the ideal cell type with which to promote myocardial regeneration. Thus far, several cells types have been investigated in animal models including, but not limit to, fetal cardiomyocytes 2, 3 , fibroblasts, skeletal myoblasts 4-7 and endothelial progenitor cells 8,9 . Results with all these cell types have generally been encouraging with regards to beneficial post-MI remodeling; albeit none have resulted in definitive differentiation into physiologically-significant, forcegenerating cardiomyocytes. Five years ago, striking reports suggested, for the first time, that bone marrow derived stem cells (hematopoietic stem cells) may have the potential to regenerate significant amounts of lost myocardium in mice following MI 10,11 , creating overwhelmingly enthusiasm and subsequent skepticism in the field of cardiac repair and regeneration. More recently, the identification of resident cardiac stem/progenitor cells by several groups, including ours 12-15 , has brought about a second wave of the scientific interest. These findings have advanced our understanding of myocardial biology and physiology and have introduced P...

Bones of contention: Marrow-derived cells in myocardial regeneration

“…In other words, things are promising at present and will likely get much better in the next few years with greater comprehension of the emerging stem cell regenerative medicine. It is easy to become enthused about relatively nascent observations of reverseengineered somatic cells, but it is far too early to become evangelical about their potential relative to what we have already got working [13]. Like so many other candidate stem cell types gone before them, capabilities and limitations of iPS cells remain to be defined, and I don't need to lecture you on the problems of ES cell-based therapy for cardiac repair [14].…”

Three-Dimensional and Biomimetic Technology in Cardiac Injury After Myocardial Infarction: Effect of Acellular Devices on Ventricular Function and Cardiac Remodelling

“…The heart possesses regenerative capacity atributed to endogenous and exogenous progenitor cell populations [25]. Thus, there is a growing interest in developing new approaches to treat MI, cardiovascular tissue engineering is currently considered as a promising alternative therapy to restore the structure and function of infarcted adult myocardium via application of a biological device, onto the ischemic tissue [26].…”

Bone as a source of organism vitality and regeneration

“…The first progeny of HSCs are multipotent progenitors that retain the ability to differentiate into all hematopoietic lineages but show a lower capacity to proliferate [59] [62] reported that mouse bone-marrow-derived cells give rise to skeletal muscle cells when transplanted into damaged mouse www.fhc.viamedica.pl muscle. Thereafter, transplanted bone marrow cells were reported to generate a wide spectrum of different cell types, including hepatocytes [63], endothelial, myocardial [64][65][66], neuronal, and glial cells [67,68]. Moreover, HSC can produce cardiac myocytes and endothelial cells [69], functional hepatocytes [70], and epithelial cells of the liver, gut, lung, and skin [71].…”