Bone Marrow–Derived Cardiomyocytes Are Present in Adult Human Heart

Deb, Arjun; Wang, Shaohua; Skelding, Kimberly A.; Miller, Dylan V.; Simper, David; Caplice, Noel M.

doi:10.1161/01.cir.0000061910.39145.f0

Cited by 335 publications

(81 citation statements)

References 13 publications

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“…These numbers are in good agreement with data from the literature, 18,19,27 although others have reported significantly higher numbers. 2 These discrepancies may be caused by the differences in tracing method (for example, tracing of prelabelled BM cells), but are more probably due to an overestimation of Y-positive cardiomyocytes among the large number of infiltrating (male) inflammatory cells.…”

Section: Discussionsupporting

confidence: 92%

“…However, the reported number of invading stem cells that, evidently, differentiate into cardiomyocytes varied considerably between the various experimental and human studies. 9,10,[14][15][16][17][18][19][20] This heterogeneity is most likely the result of an overestimation of host-derived cardiomyocytes, due to the presence of large number of infiltrating host-derived inflammatory cells and/or to the application of a variety of different detection techniques.…”

Section: Introductionmentioning

confidence: 99%

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Stem cell-derived cardiomyocytes after bone marrow and heart transplantation

Weger

Verbrugge

Bruggink

et al. 2007

Bone Marrow Transplant

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Cardiomyocytes are a stable cell population with only limited potential for renewal after injury. Tissue regeneration may be due to infiltration of stem cells, which differentiate into cardiomyocytes. We have analysed the influx of stem cells in the heart of patients who received either a gender-mismatched BMT (male donor to female recipient) or a gender-mismatched cardiac transplant (HTX; female donor to male recipient). The proportion of infiltrating cells was determined by Y-chromosome in situ hybridization combined with immunohistochemical cell characterization. In BM transplanted patients and in cardiac allotransplant recipients, cardiomyocytes of apparent BM origin were detected. The proportions were similar in both groups and amounted up to 1% of all cardiomyocytes. The number of stem cell-derived cardiomyocytes did not alter significantly in time, but were relatively high in cases where large numbers of BMderived Y-chromosome-positive infiltrating inflammatory cells were present. The number of Y-chromosome-positive endothelial cells was small and present only in small blood vessels. The number of BM-derived cardiomyocytes in both BMT and HTX is not significantly different between the two types of transplantation and is at most 1%.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Stem cell-derived cardiomyocytes after bone marrow and heart transplantation

Weger

Verbrugge

Bruggink

et al. 2007

Bone Marrow Transplant

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“…Initial reports suggesting transdifferentiation of cells delivered to target tissues into the organ host cells have been followed by reports of cell fusion and by claims of no meaningful cell-cell transformation, leading to a major controversy. The evidence for trans-differentiation in vivo is contradictory with some studies finding evidence for phenotypic switches following injections of cells into the heart or other organs [9][10][11] while others cannot demonstrate this phenomenon. [12][13][14][15] The reasons for these discrepancies are manifold and include both technical as well as poorly understood biological issues.…”

Section: Reported Study Results Vary and Improved Laboratory Techniqumentioning

confidence: 83%

Progress and prospects: Cell based regenerative therapy for cardiovascular disease

2005

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Experimental and clinical studies are progressing simultaneously to investigate the mechanisms and efficacy of progenitor cell treatment after an acute myocardial infarction and in chronic congestive heart failure. Multipotent progenitor cells appear to be capable of improving cardiac perfusion and/or function; however, the mechanisms still are unclear, and the issue of whether or not trans-differentiation occurs remains unsettled. Both experimentally and clinically, cells originating from different tissues have been shown capable of restoring cardiac function, but more recently multiple groups have identified resident cardiac progenitor cells that seem to participate in regenerating the heart after injury. Clinically, cells originating from blood or bone marrow have been proven to be safe whereas injection of skeletal myoblasts has been associated with the occurrence of ventricular arrhythmias. Myoblasts can transform into rapidly beating myotubes; however, thus far convincing evidence for electro-mechanical coupling between myoblasts and cardiomyocytes is lacking. Moving forward, mechanistic studies will benefit from the use of genetic markers and Cre/lox reporter systems that are less prone to misinterpretation than fluorescent antibodies, and a more convincing answer regarding therapeutic efficacy will come from adequately powered randomized placebo controlled trials. Gene Therapy (2006) 13, 659-671.

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“…To investigate whether circulating bone marrow-derived cells are capable of de novo cardiomyocyte formation, Deb et al 57 analyzed hearts of 4 female patients who had undergone sex-mismatched bone marrow transplantation. The time interval between transplantation and death was 35, 480, 510, and 600 days.…”

Section: Engraftment Of Bone Marrow Stem or Progenitor Cells In The Hmentioning

confidence: 99%

Stem and Progenitor Cell Therapy for Pulmonary Arterial Hypertension: Effects on the Right Ventricle (2013 Grover Conference Series)

2015

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In experimental animals and in patients with pulmonary arterial hypertension (PAH), a wide spectrum of structural and functional conditions is known that may be responsible for the switch of a state of "compensated" right ventricular (RV) hypertrophy to a state of RV failure. In recent years, therapy with differentiated cells, endothelial progenitor cells, and mesenchymal stem cells has been shown to cause partial or complete reversal of pathological characteristics of PAH. The therapeutic effects of stem or progenitor cell therapy are considered to be (1) paracrine effects from stem or progenitor cells that had engrafted in the myocardium (or elsewhere), by compounds that have anti-inflammatory, antiapoptotic, and proangiogenic actions and (2) unloading effects on the right ventricle due to stem or progenitor cellinduced decrease in pulmonary vascular resistance and decrease in pulmonary artery pressure. Pulmonary arterial hypertension (PAH) is associated with right ventricular (RV) hypertrophy (RVH) or RV failure (RVF), considered to be the result of RV pressure overload. Pharmacotherapy, gene therapy, stem and progenitor cell therapy, and combinations of these treatment modalities have been shown to treat PAH, by lowering pulmonary artery pressure, lowering RV weight, and relieving RVF, thereby improving exercise capacity and life span. 1 Here we review the evidence that, in animals with PAH, stem and progenitor cell therapy leads to lower RV weight and relief of RVF by mechanisms that can be ascribed to (1) lowering of RV afterload and (2) direct effects of the stem and progenitor cells on RV myocardial structure and function. RVH DUE TO PAH-INDUCED RV OVERLOAD: PATHOLOGICAL OR PHYSIOLOGICAL HYPERTROPHY?Originally, left ventricular (LV) hypertrophy (LVH) secondary to pressure overload was considered to be "compensatory," 2 but several studies have clearly demonstrated that LVH is a risk factor and has unfavorable prognostic implications. [3][4][5] On the other hand, the athlete's heart often implies the presence of LVH, but this LVH is considered an adaptation to volume overload that occurs during longlasting rowing, running, and cycling. 6 To date, the healthy aspects of exercise training have been documented firmly and are not restricted to healthy individuals, such as athletes, but even to patients with heart failure. 7,8 The two main forms of myocardial hypertrophy are often termed "pathological" hypertrophy, as occurs secondary to pressure overload, and "physiological" hypertrophy, as occurs in the athlete's heart. Pathological and physiological hypertrophy have been characterized in detail, 9-13 and the most significant differences are found in the membrane receptor and signaling pathways that convey the message to the nucleus, where hypertrophy is effectuated with or without changes in gene expression. In pathological hypertrophy, Ca 2+ -dependent calcineurin activation and calcineurin-induced dephosphorylation of

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Bone Marrow–Derived Cardiomyocytes Are Present in Adult Human Heart

Abstract: These data establish for the first time human bone marrow as a source of extracardiac progenitor cells capable of de novo cardiomyocyte formation.

Cited by 335 publications

References 13 publications

Stem cell-derived cardiomyocytes after bone marrow and heart transplantation

Stem cell-derived cardiomyocytes after bone marrow and heart transplantation

Progress and prospects: Cell based regenerative therapy for cardiovascular disease

Stem and Progenitor Cell Therapy for Pulmonary Arterial Hypertension: Effects on the Right Ventricle (2013 Grover Conference Series)

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