Cellular repopulation of myocardial infarction in patients with sex-mismatched heart transplantation*1

Höcht-Zeisberg, Elisabeth; Kahnert, Henning; Guan, Kaomei; Wulf, Gerald; Hemmerlein, Bernhard; Schlott, Thilo; Tenderich, Gero; Körfer, Reiner; Raute-Kreinsen, U; Hasenfuß, Gerd

doi:10.1016/j.ehj.2004.01.017

Cited by 73 publications

(45 citation statements)

References 19 publications

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“…A three-dimensional screening by confocal laser scan microscopy will also prevent the misinterpretation of infiltrating cells beneath the cardiomyocytes, which otherwise are scored as positive cardiomyocytes. 20 This study indicated that there tends to be a positive correlation between the number of stem cell-derived cardiomyocytes and the proportions of infiltrating cells. Such a cellular infiltrate, occurring during an inflammatory response, may take with it a certain number of stem cells, which ultimately can differentiate into cardiomyocytes.…”

Section: Discussionmentioning

confidence: 77%

“…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: Discussionmentioning

confidence: 77%

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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“…In sex-mismatched heart transplant and using Y chromosome fluorescence in situ hybridization, studies have shown a cardiac chimerism caused by migration of recipient cells to the grafted heart. 33,34 The field of forensics has relied on STR loci for identification of suspects and human remains. In theory, testing haplotypes could allow one to identify the presence of suspect in a large mixture of DNAs, such as in polysuspect cases.…”

Section: The Human Genome Contains Clusters Of Snps That Can Be Amplimentioning

confidence: 99%

Haplotype Counting by Next-Generation Sequencing for Ultrasensitive Human DNA Detection

Debeljak

Freed

Welch

et al. 2014

The Journal of Molecular Diagnostics

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The ASCP designates this journal-based CME activity ("JMD 2014 CME Program in Molecular Diagnostics") for a maximum of 48 AMA PRA Category 1 Credit(s)ä. Physicians should only claim credit commensurate with the extent of their participation in the activity. CME Disclosures: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Human identity testing is critical to the fields of forensics, paternity, and hematopoietic stem cell transplantation. Most bone marrow (BM) engraftment testing currently uses microsatellites or short tandem repeats that are resolved by capillary electrophoresis. Single-nucleotide polymorphisms (SNPs) are theoretically a better choice among polymorphic DNA; however, ultrasensitive detection of SNPs using next-generation sequencing is currently not possible because of its inherently high error rate. We circumvent this problem by analyzing blocks of closely spaced SNPs, or haplotypes. As proof-ofprinciple, we chose the HLA-A locus because it is highly polymorphic and is already genotyped to select proper donors for BM transplant recipients. We aligned common HLA-A alleles and identified a region containing 18 closely spaced SNPs, flanked by nonpolymorphic DNA for primer placement. Analysis of cell line mixtures shows that the assay is accurate and precise, and has a lower limit of detection of approximately 0.01%. The BM from a series of hematopoietic stem cell transplantation patients who tested as all donor by short tandem repeat analysis demonstrated 0% to 1.5% patient DNA. Comprehensive analysis of the human genome using the 1000 Genomes database identified many additional loci that could be used for this purpose. This assay may prove useful to identify hematopoietic stem cell transplantation patients destined to relapse, microchimerism associated with solid organ transplantation, forensic applications, and possibly patient identification. Myeloablative conditioning and allogeneic stem cell transplantation have historically been limited to the treatment of lethal hematological malignancies in children or young adults. More recently, with the advent of highly immunosuppressive, nonmyeloablative regimens, the clinical use of allogeneic stem cell transplantation has expanded to include older, less fit patients with hematological malignancies and patients with nonmalignant disorders, such as sickle-cell disease.1e4 Nonmyeloablative conditioning regimens offer the additional safeguard of recovery of autologous hematopoiesis in the event of graft rejection and may be a safer option in patients at risk for immune-mediated rejection of the donor graft.Chimerism testing at set intervals is an effective method for detecting graft rejection or recurrence of the original hematopoietic neoplasm after allogeneic hematopoietic stem cell transplantation (

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“…In vivo, however, although the degree of differentiation still remains controversial, many reports have shown cardiac differentiation potential from BM-derived cells. This evidence was supported by human sexmismatched heart transplantation, where cardiac chimerism was determined in transplanted patients [23][24][25][26]. The percentage of contribution however, was very low in all these cases (0.02% to 0.07%) which raised questions about the physiological relevance of their contribution.…”

Section: Bone Marrow-derived Scmentioning

confidence: 89%

Stem Cells and Cardiac Disease: Where are We Going?

Pelacho

Prósper

2008

CSCR

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During the last 10 years we have witnessed the development of a new field in research termed Stem Cell Therapy. Classically, it was considered that cells had a limited division and differentiation ability; however, this dogma was challenged when new exciting results about cell multi/pluripotency were presented to the scientific community. It was found that cells from one adult tissue source were able to originate cells of a very different type. The possibility of transplanting these cells into damaged organs with the aim of substituting sick or dead tissue, triggered many studies to understand the plasticity of the stem cells and their potential in pathological situations. Nowadays, much more is understood about stem cells, although of course, many questions, especially about their mechanism of action, still need to be answered. Their benefit after transplantation has been shown experimentally and even clinically in some cases; however, the degree of stem cell contribution through their own differentiation into the transplanted tissue, has turned out to be generally low, and increasing evidence indicates that a trophic effect must play an important role in such a benefit. A better understanding of the paracrine mechanisms involved could be of great relevance in order to develop new therapies focused on stimulating endogenous cells. On the other hand, more sophisticated methods for cell transplantation combined with bio-engineering techniques have been devised in cardiac disease models. In this review we will try to provide a critical overview of the stem cell studies performed until now and to discuss some of the questions raised about the mechanisms that are involved in their putative reparative effect in cardiovascular diseases, and their origin.

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Cellular repopulation of myocardial infarction in patients with sex-mismatched heart transplantation*1

Abstract: Myocardial infarction enhances the invasion of extracardiac progenitor cells and their regeneration of endothelial cells. However, a significant differentiation into cardiomyocytes as a physiological mechanism of postischaemic regeneration does not occur in transplanted patients.

Cited by 73 publications

References 19 publications

Stem cell-derived cardiomyocytes after bone marrow and heart transplantation

Stem cell-derived cardiomyocytes after bone marrow and heart transplantation

Haplotype Counting by Next-Generation Sequencing for Ultrasensitive Human DNA Detection

Stem Cells and Cardiac Disease: Where are We Going?

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