Ectopic Ossification in the Scar Tissue of Rats with Myocardial Infarction

Ribeiro, Karla Consort; Mattos, Elisabete C.; Werneck-de-Castro, João Pedro; Ribeiro, Vanessa Pinho; Costa-e-Sousa, Ricardo H.; Miranda, Amarildo; Olivares, Emerson Lopes; Farina, Marcos; Mill, José Geraldo; Goldenberg, Regina Coeli dos Santos; Masuda, Masako Oya; Carvalho, Antônio Carlos Campos de

doi:10.3727/000000006783981864

Cited by 14 publications

(7 citation statements)

References 32 publications

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“…We here addressed these important questions by using (1) genetically labeled cells, (2) whole BM and different fractions of BM-derived cell populations, (3) careful characterization of the cell biologic properties of the MSCs and their in vitro differentiation potential, (4) different types of myocardial infarction models, (5) a large number of different control conditions, and (6) direct injection of cells as well as BM mobilization. Our present study in mice and the earlier in rats 24 could not identify, as reported recently for rat hearts, 23 a high incidence of calcifications after myocardial infarction independent of cell transplantation.…”

Section: Discussioncontrasting

confidence: 80%

“…This excluded tissue-derived heterotopic calcifications as underlying cause that were found after acute myocardial infarction in a few human patients 21,22 and more frequently in rats. 23 Direct involvement of the transplanted cells in the generation of calcifications/ossifications rather than an unspecific tissue response was clearly supported by the observation that transplanted cells generated osteocalcin at an early stage, whereas at later stages the massive bone formation led to decellularized central areas. Calcifications after injection of BM cells into the infarcted rat myocardium were reported earlier.…”

Section: Discussionmentioning

confidence: 91%

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Potential risks of bone marrow cell transplantation into infarcted hearts

Breitbach

Bostani

Roell

et al. 2007

Blood

574

391

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Cellular replacement therapy has emerged as a novel strategy for the treatment of heart failure. The aim of our study was to determine the fate of injected mesenchymal stem cells (MSCs) and whole bone marrow (BM) cells in the infarcted heart. MSCs were purified from BM of transgenic mice and characterized using flow cytometry and in vitro differentiation assays. Myocardial infarctions were generated in mice and different cell populations including transgenic MSCs, unfractionated BM cells, or purified hematopoietic progenitors were injected. Encapsulated structures were found in the infarcted areas of a large fraction of hearts after injecting MSCs (22 of 43, 51.2%) and unfractionated BM cells (6 of 46, 13.0%). These formations contained calcifications and/or ossifications. In contrast, no pathological abnormalities were found after injection of purified hematopoietic progenitors ( IntroductionSevere heart failure is caused by an irreversible loss of cardiomyocytes and has a poor prognosis regardless of the underlying disease. 1 Since medical treatment is of only limited help, solid organ transplantation was considered until recently the only effective therapy. However, as organ availability decreases, there is an urgent need for alternative treatments. Studies in mice have suggested that myocardial infarctions can be repaired following transplantation of bone marrow (BM)-derived cells into the lesioned myocardium, either through generation of cardiomyocytes or angiogenesis. 2 An underlying assumption of this approach is that the environment will instruct as well as restrict the developmental fate of adult stem cells after their transplantation (for review see Laflamme and Murry 3 or Murry et al 4 ). However, the original findings in mice have recently been put into question, since we and others have demonstrated that BM-derived hematopoietic cells do not transdifferentiate into cardiomyocytes in the infarcted myocardium. [5][6][7] In this study, we focused on the potential of an enriched population of mesenchymal stem cells (MSCs) that are known to be present in the BM and are multipotent. 8 In contrast to hematopoietic progenitors, MSCs are easy to obtain and to expand in vitro and have therefore emerged as attractive candidates for cellular therapies in heart and other organs. 9,10 However, recent reports have questioned their "transdifferentiation" potential after injection into the myocardium and rather propose benefits via paracrine mechanisms. 11,12 Herein, we investigated and provide novel insights with regard to the fate of enriched populations of BM-derived MSCs as well as whole BM cells comprising both hematopoietic and mesenchymal progenitors after transplantation into the infarcted heart. Materials and methodsAll experiments were approved by the local ethics care committees at Bonn, Cologne, and Lund Universities. Cells for transplantation were isolated from transgenic C57Bl/6 mice expressing enhanced green fluorescent protein (EGFP) under control of the ␤-actin promoter. 13 Cell isolation and cultu...

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Section: Discussioncontrasting

confidence: 80%

Section: Discussionmentioning

confidence: 91%

Potential risks of bone marrow cell transplantation into infarcted hearts

Breitbach

Bostani

Roell

et al. 2007

Blood

574

391

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“…Further, our data supports a recently published paper by Ribeiro et al . in 2006, in which they showed that chondro-osteogenic differentiation can take place in the Wistar rat heart independent of animal treatment with bone marrow cells 28.…”

Section: Discussionmentioning

confidence: 99%

Calcification after myocardial infarction is independent of amniotic fluid stem cell injection

Delo

Guan

Zhan

et al. 2011

Cardiovascular Pathology

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Ischemic heart disease remains one of the most common causes of mortality in developed countries. Recently, stem cell therapy is being considered for treating ischemic heart diseases. On the other hand, there has been evidence of chondro-osteogenic mass formation after stem cell injection in the heart. In a recent publication, Chiavegato et al. has suggested that amniotic fluid derived stem (AFS) cells cause chondro-osteogenic masses in the infarcted heart. The goal of the current study was to further examine the formation of such masses, specifically, the role of AFS cells in this process. Our results confirm the presence of similar bone-like masses in the left ventricular wall of infarcted rats; however, this phenomenon occurred independent of AFS cell injection into the myocardium. Moreover, AFS cell injection did not increase the presence of chondro-osteogenic masses. Echocardiographic analysis of large infarctions in rats frequently revealed the presence of echogenic structures in the left ventricular wall. We further demonstrated a significant relationship between the infarction size and chondro-osteogenic formation and subsequently decrease in cardiac function. Collectively, our study indicates that chondroosteogenic differentiation can take place in infarcted rat heart independent of cell injection. These results have significant implications for future design and testing of stem cell therapy for treatment of cardiac muscle diseases.

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“…Therefore, ectopic calcification was perceived as the end stage of affected tissue and was not considered important (8,9). Although ectopic calcification is considered benign, it is often a cause of various other diseases and patient prognosis is much worse when calcification is present (10,11). Recently, studies have made significant progress on elucidating the biology of normal bone metabolism, which has facilitated research on ectopic calcification at the same time.…”

Section: Ectopic Calcificationmentioning

confidence: 99%

Recent Advances in Research on Human Aortic Valve Calcification

Furukawa

2014

J Pharmacol Sci

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Abstract. Aortic valve calcification can aggravate aortic stenoses, and it is a significant cause of sudden cardiac death. The increasing number of patients with age-related calcification is a problem in developed nations. However, the only treatment option currently available is highly invasive cardiac valve replacement. Therefore, clarification of the etiology of calcification is urgently needed to develop drug therapies and prevention methods. Recent studies have revealed that calcification is not a simple sedimentation of a mineral through a physicochemical phenomenon; various factors dynamically contribute to the mechanism. Further, we are finally beginning to understand the cellular origins of calcification, which had been unclear for a long time. Based on these findings that help to clarify potential drug targets, we expect to establish drug therapies that reduce the stress on patients. In this paper, I introduce the latest findings on cells that are most likely to contribute to calcification and on calcification-related factors that may lead to the development of drug therapies.

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Ectopic Ossification in the Scar Tissue of Rats with Myocardial Infarction

Cited by 14 publications

References 32 publications

Potential risks of bone marrow cell transplantation into infarcted hearts

Potential risks of bone marrow cell transplantation into infarcted hearts

Calcification after myocardial infarction is independent of amniotic fluid stem cell injection

Recent Advances in Research on Human Aortic Valve Calcification

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