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J Thorac Cardiovasc Surg 2000;119:1169-1175
© 2000 The American Association for Thoracic Surgery
SURGERY FOR ACQUIRED CARDIOVASCULAR DISEASE |
From the Department of Cardiovascular Surgery, Hôpital Bichat; INSERM U-127, Hôpital Lariboisière; INSERM U-523 Institut de Myologie, Groupe Hospitalier Pitié-Salpétrière, and the Research in Imaging Laboratory, Faculté de Médecine Necker-Enfants Malades, Paris, France.
Address for reprints: Philippe Menasché, MD, Department of Cardiovascular Surgery, Hôpital Bichat, 46, rue Henri Huchard, 75018 Paris, France.
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Abstract |
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 Top Abstract IntroductionMaterial and methods Results Discussion Appendix: Discussion References |
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Introduction |
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TopAbstractIntroductionMaterial and methods Results Discussion Appendix: Discussion References |
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1 As such, it represents one of the greatest challenges in public health for the next century. Standard surgical procedures, such as coronary artery bypass grafting, mitral valvuloplasty, and/or valve replacement, have been used to treat patients with advanced left ventricular dysfunction with good initial results. However, these procedures only prevent further myocardial deterioration and do not act on the underlying disease, which is myocardial fibrosis. At the opposite end of the spectrum, cardiac transplantation provides a radical therapy, but organ shortage, along with strict eligibility criteria, mandate the search for alternate treatments in cases in which a substantial portion of the myocardium has been irreversibly destroyed.
Among those treatments, cellular transplantation has emerged as a possible means of increasing the number of contractile elements in damaged myocardium. We 2 and others 3,4 have previously shown that fetal cardiomyocyte transplantation improves the function of ischemic and globally failing hearts. In a clinical perspective, however, the use of fetal cardiomyocytes raises several issues, including availability, immunogenicity, and ethics. These considerations have led to the search for alternate cell types among which skeletal muscle progenitors (myoblasts, also known as satellite cells) are attractive candidates because (1) they can re-enter the cell cycle, and thus should augment the number of contractile elements in the host myocardium, and (2) they can be used as autografts, thereby avoiding any immunologic conflict. The present study was therefore designed to assess, in a rat model of coronary artery ligation, whether the functional benefits of intramyocardially injected fetal cardiomyocytes on postinfarct function could be equaled by skeletal myoblasts.
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Material and methods |
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TopAbstractIntroductionMaterial and methods Results Discussion Appendix: Discussion References |
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Fetal cardiomyocyte isolation procedure
Cardiomyocytes from fetal rat hearts were isolated and purified as previously described. 2 Twenty-day-old embryos (Iffa Credo, les Oncins, France) were removed, and their hearts were enzymatically digested. The pellet was then resuspended in a culture medium (68% Dulbecco’s modified Eagle medium [DMEM], 17% medium 199, 10% horse serum, and 5% calf serum in the presence of 100 IU/mL penicillin, 10–7 mol/L triiodothyronine, 100 mg/mL streptomycin, and 10–9 mol/L insulin) and diluted to achieve a final concentration of 5 x 106 cells/150 µL to be used for the intramyocardial injections. This procedure was performed on the day of transplantation and has previously been shown to preserve viability of cells. 2
Neonatal myoblast isolation procedure
Primary muscle cell cultures were prepared from newborn Wistar rats (Iffa Credo). The 4 legs were skinned and dissociated enzymatically at 37°C by using first collagenase IA (2 mg/mL for 1 hour; Sigma Chemical Company, St Louis, Mo) and trypsin (0.25% for 20 minutes; Gibco BRL, Life Technologies, Inc, Rockville, Md). The cells were grown in 57% DMEM, 27% Earle’s 199 medium, 15% fetal calf serum, and 1% antibiotics (all components from Gibco). The cells were harvested and frozen on the second day. Twenty-five million cells were prepared from one newborn. A homogeneous stock of cells was prepared on the same day from 20 newborns. The cells from this stock were used throughout the transplantation experiments. On the day of transplantation, the cells were rapidly thawed and washed 3 times in injection medium, which contained 75% DMEM, 24% 199, and 0.5% bovine serum albumin (Fraction V, Sigma). The cell death did not exceed 5%, as assessed by trypan blue staining. Samples of 5 x 106 cells were prepared and kept on ice until transplantation.
After thawing, some samples were plated onto 12-well dishes in growth medium for desmin immunolabeling. Eighteen hours after seeding, the cells were fixed in methanol. Nonspecific labeling was blocked by use of a mixture of 5% horse serum and 5% fetal calf serum in phosphate-buffered saline solution (PBS). The cells were incubated with anti-desmin antibody (clone 33, 1:300, 1 hour; Dako, Trappes, France) and then with Cy3-conjugated anti-mouse immunoglobulin antibody (Jackson, 1:300, 1 hour; Asnières, France). With the use of an inverted microscope, several fields were randomly photographed both under fluorescent illumination and phase contrast. The percentage of myogenic cells was obtained by dividing the total number of cells counted on phase contrast pictures by the total number of desmin-positive cells counted on immunofluorescence pictures.
Myocardial infarction model
Male rats weighing an average of 230 g were anesthetized with ketamine (50 mg/kg body weight administered intraperitoneally) and xylazine (5 mg/kg body weight administered intraperitoneally) and tracheally ventilated. Each heart was exposed through a lateral thoracotomy. The left coronary artery was then identified and occluded proximally by means of a 7-0 polypropylene snare (Ethicon, Inc, Somerville, NJ).
Functional assessment
One week after myocardial infarction and 1 month after cellular transplantation, cardiac function was studied by echocardiography. Left ventricular dimensions and function were assessed by 2-dimensional echocardiography (Sequoia; Acuson Corp, Mountain View, Calif) equipped with a 15-MHz phased-array linear transducer (15L8), allowing a 160-Hz maximal frame rate and specifically designed for cardiac ultrasonic studies in murine models. The probe was positioned on the left anterior side of the chest after the precordium was shaved, and the rat was placed on a warming pad. The heart was imaged in 2-dimensional mode at a minimum depth setting and image size by means of the RES enhanced resolution imaging function in the long-axis view of the left ventricle, taking care to include the mitral and aortic valves and the apex. Care was taken to avoid excessive pressure. When a correct image was obtained with well-defined continuous interfaces for the septum and posterior wall at the higher frame rate, a numeric acquisition was performed on the hard disk of the echocardiographic machine. The following measurements were then performed on-line at end-diastole (at the time of apparent maximal cavity dimension) and at end-systole (at the time of maximum anterior motion of the posterior wall) by use of the cine-loop feature to retrospectively obtain adequate visualization of the following fast-beating hearts (300-400 beats/min): maximal left ventricular long-axis lengths and endocardial area tracings (by using the leading edge method). These data were then used to calculate left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) by using the single-plane area-length method: EF = LVEDV – LVESV/LVEDV, where EF is ejection fraction. All measurements were made by one experienced observer who was blinded to the treatment group. Measurements were averaged over 3 to 5 consecutive cardiac cycles. Intraobserver variability was assessed at baseline by 2 sets of measurements in 10 randomly selected rats, and the coefficient of correlation and the standard error of estimate were calculated according to the method of Bland and Altman. 5
Experimental groups
One week after coronary artery ligation, left ventricular function was echocardiographically assessed. Thereafter, rats (n = 42) were reoperated on through a median sternotomy and randomly allocated to 1 of the following 3 groups. In the control group (n = 15) 150 µL of culture medium alone (without cells) was injected subepicardially by using a 30-gauge needle in the core of the infarcted area. The fetal group (n = 11) received an equivalent volume supplemented with fetal cardiomyocytes (5 x 106 cells in 150 µL of culture medium) at the same time point and in the same location. The myoblast group (n = 16) also received an equivalent volume supplemented with neonatal myoblasts (5 x 106 cells in 150 µL of culture medium). Differences in the incidence of deaths that occurred intraoperatively or therafter account for the observation that sample sizes were unequal. All animals received cyclosporine (INN: ciclosporin) throughout the study (15 mg · kg–1 · d–1 administered intraperitoneally; Sandoz Pharmaceutical Corporation, Basel, Switzerland), starting 3 hours before anesthetic induction. One month after the transplantation, left ventricular function was assessed again by means of echocardiography.
Pathology
Twenty-four hours after the last echocardiographic study, the rats were killed by injecting an overdose of ketamine and xylazine. The hearts were removed and rapidly rinsed in PBS. They were snap-frozen in isopentane cooled with nitrogen. Serial sections 8-µm thick were prepared by use of a cryostat and subsequently processed for standard histology (hematoxylin-eosin staining) and immunohistofluorescence (desmin, myosin, and connexin staining). The fate of the transplanted myoblasts was investigated by looking for the presence of cardiac- or skeletal-specific antigens on serial sections of heart tissue. The sections were rinsed in PBS and fixed with cold methanol for 5 minutes, and the nonspecific labeling was blocked with a mixture of 5% horse serum and 5% fetal calf serum in PBS for 30 minutes. The sections were incubated with the primary antibody for 1 hour at room temperature. We used the mouse monoclonal antibody directed against desmin (1:300, Dako), the mouse monoclonal antibody directed against the embryonic myosin heavy chain (EMHC; a gift of Dr Gillian Buttler-Browne, Paris, France; dilution 1:5), and a polyclonal rabbit anti-connexin 43 antibody (gift of Dr Daniel Gros, Marseille, France; dilution 1:100). After several washes, the sections were incubated with the Cy3-conjugated anti-mouse or anti-rabbit immunoglobulin antibodies (1:200, Jackson) for 1 hour at room temperature. The sections were mounted in PBS-glycerol (1:1).
Data analysis
For statistical analysis, we used SAS procedures (Statistical Analysis System, Cary, NC). Echocardiographic data recorded in the 3 groups before and after myocardial injections were compared by means of 1-way analysis of variance. Within each group, echocardiographic data were compared before and 1 month after myocardial injections by paired t tests. Mean EFs at 1 month were compared between groups after adjustment for basal EF. If analysis of variance was significant, groups were compared by using a Scheffé test. Data are given as means ± SEM.
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Results |
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TopAbstractIntroductionMaterial and methods Results Discussion Appendix: Discussion References |
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Functional assessment
Baseline pretransplant echocardiographic data were not different among the 3 groups (Table I). One month later, the major result is that transplantation of either fetal cells or skeletal myoblasts improved EF compared with control hearts (Table I). This was paralleled by a significant increase in LVEDV in control rats (from 0.46 ± 0.02 at baseline to 0.68 ± 0.04 at 1 month, P = .0007), whereas remodeling was limited in the transplanted hearts with LVEDV, being 0.45 ± 0.03 at baseline and 0.58 ± 0.06 at 1 month (P = .038) in the fetal group and 0.52 ± 0.04 at baseline and 0.6 ± 0.05 at 1 month (P = .11) in the myoblast group.
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). Of note, these post-transplantation functional data were recorded under similar conditions of heart rate (300 ± 19 beats/min, 293 ± 15 beats/min, and 308 ± 22 beats/min in the control, fetal, and myoblast groups, respectively).
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, B ). These structures were typical of myotubes and muscle fibers, and they were aligned along either the long or the short axis of the heart. The smallest stained cells were probably committed myoblasts. Desmin staining of serial sections confirmed the muscular nature of the structures for EMHC (Fig 2, C ). Desmin staining also revealed the presence of cardiac tissue surrounding the skeletal tissue at the borders of the infarcted zone; this cardiac tissue did not express EMHC. Finally, connexin 43 was expressed by the cardiac cells surrounding the skeletal muscle; however, the myoblasts, myotubes, and skeletal muscle fibers did not express connexin 43 (Fig 2, D ). In summary, engrafted myoblasts were identified within and at the borders of the fibrous scar by their positive staining for desmin and EMHC (a specific marker of skeletal myoblasts) and could thus be differentiated from the surrounding host cardiomyocytes, which only stained for desmin (a nonspecific marker of muscular cells).
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Discussion |
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TopAbstractIntroductionMaterial and methods Results Discussion Appendix: Discussion References |
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Echocardiographic assessment of function
Because rat hearts beat at a fast rate and because of the limitation of M-mode echocardiography in assessing volumes and performance in infarcted ventricles, we used a 2-dimensional echocardiographic machine, allowing a numeric acquisition of a maximum of 160 images per second and yielding more than 25 heart scans at a heart rate of 300 beats/min. Previous necropsy findings have shown that the left ventricle in rats has an elliptical shape, which justifies that volume measurements were based on an elliptical model of left ventricular geometry. 6 We used the single-plane area-length method, which has been shown in human infarcted hearts to be more accurate than those relying on M-mode measurements. The echocardiographic method of volume calculation was based on a single plane model, which could underestimate the extent of infarction. This method was preferred to biplane methods, which have not yet been validated in infarcted rats and are difficult to apply in practice because of cavity distortion after large anterior infarction. Thus in this study differences between groups might have only been underestimated.
Fetal cardiomyocyte transplantation
The functional benefits of fetal cell transplantation have been well established in myocardial infarction models created by cryonecrosis 3 or coronary artery ligation 2 and in which function was assessed by in vitro Langendorff perfusion studies 3 or in vivo echocardiographic measurements. 2 More recently, these observations made in regionally ischemic preparations have been extended to the setting of global heart failure induced by anthracyclines. 4 The present data extend these findings mechanistically.
Namely, the fact that intramyocardially injected fetal cardiomyocytes primarily limited left ventricular dilation strongly suggests that the elastic properties of these cells played a major role in the overall improvement of function. 7 Indeed, this improvement was probably underestimated because of the expectedly limited effects of cell transplantation in rats with initially small infarcts that did not tend to substantially enlarge over time. Conversely, the greatest benefits were seen in those animals with the largest infarcts and the consequently lowest pretransplant EFs, which supports the potential relevance of this procedure to patients with severe ischemic cardiomyopathy. However, apart from limitation of remodeling, other mechanisms could account for the functional benefits of fetal cardiomyocyte transplantation. For example, these cells have been shown to establish gap junctions with those of the recipient myocardium, 8 which should allow them to beat synchronously with adjacent cells and thus directly contribute to enhanced contractility. Indeed, analysis of our data in relation with the pretransplant functional status of hearts raises the possibility that a contention mechanism could prevail in cases of initially small infarcts, whereas direct systolic assistance would be additionally involved in large infarcts. It is also conceivable that intracardiac grafts could act as platforms releasing growth factors, angiogenic factors, or both. This hypothesis is indeed supported by two lines of evidence: (1) intramyocardially implanted cardiomyocytes increase the density of capillaries and arterioles 9 and (2) locally injected cells improve global heart function, although they do not seem to migrate away from the implant sites, 10,11 which could be consistent with paracrine effects exerted by cell-derived mediators.
A major issue raised by fetal cardiomyocyte transplantation is tracing of the injected cells within the host myocardium. This is due to the fact that fetal cardiomyocytes lose their characteristic phenotypic patterns over time and become progressively indistinguishable from adult host cardiomyocytes. The intramyocardial injections of genetically labeled cells expressing ß-galactosidase activity has been the most common means of identifying them once they have been engrafted into the recipient heart. However, despite immunossupressive therapy, the expression of ß-galactosidase can be highly immunogenic 12 and, through this mechanism, can adversely affect function. Thus to avoid confounding of our echocardiographic measurements by this factor, we made no attempt to label injected fetal cells, assuming that we 2 and others 8,7,3 have previously documented their ability to form stable intracardiac grafts.
Skeletal myoblast transplantation
Myoblasts feature several advantages for cellular transplantation, including their capacity to proliferate. Neonatal myoblasts have thus been shown to replicate in the recipient myocardium until 1 week after grafting. 11 Furthermore, although most engrafted myoblasts differentiate into mature fibers, some of them might become quiescent established satellite cells that could participate in tissue repair in cases of subsequent ischemic episodes. 11
Our data confirm that neonatal skeletal myoblasts can be successfully engrafted in ischemically damaged myocardium, can limit infarct expansion, and can improve 1-month EF compared with values recorded before transplantation, as well as those yielded by nontransplanted control animals at a time-matched study point (ie, 1 month after injection of the culture medium alone). In the present study neonatal myoblasts were used to enhance the efficacy of in vitro expansion before implantation. Furthermore, grafting allogenic cells also provided the opportunity to provide cyclosporine immunossupression under the same conditions as those used in the fetal cardiomyocyte transplantation experiments. This was deemed methodologically important to avoid between-group comparisons of functional outcome to be confounded by the intrinsic effects of cyclosporine on postinfarct myocyte hypertrophy. 13 However, in a rabbit model of cryonecrosis, Taylor and associates 14 have shown that injections of autologous adult myoblasts were equally successful in improving systolic and diastolic function, as assessed by ultrasonic dimension transducers. In this study a causal relationship between the presence of myoblasts and outcome was clearly established in that function was only found to improve in hearts that were successfully engrafted.
The mechanism by which skeletal myoblast transplantation is functionally beneficial remains elusive. Chiu and coworkers 15 have hypothesized that implanted satellite cells can undergo a milieu-induced differentiation that leads them to acquire a cardiac-like phenotype. This hypothesis is largely based on the observation by these authors 15 and others 14 of structures resembling intercalated disks between transplanted myoblasts. The influence of the cardiac environment on the phenotypic changes of engrafted cells is further suggested by their conversion to fatigue-resistant slow-twitch fibers. 11,16 However, implanted myoblasts fail to express cardiac-specific myosin heavy chain up to 3 months after transplantation. 11 The formation of intercaleted disks between cardiac host cells and donor cells labeled with a reporter gene has been unambiguously reported only in the case in which a permanent mouse myogenic cell line (C2C12) was injected into a noninfarcted mouse myocardium. 17 Our present results argue against a classical pathway of electrical coupling of cardiac and skeletal tissue in vivo because engrafted myoblasts, identified within and around the fibrotic tissue by their positive staining for the skeletal muscle–specific myosin heavy chain, failed to express connexin 43 on their sarcolemma. Taken together, these data suggest that some structures may develop over time that mechanically tether implanted myoblasts to the adjacent host cardiomyocytes. Conversely, gap junction–supported electrical coupling, which is a prerequisite for transplanted cells to provide synchronized mechanical support, is more unlikely to occur.
Interestingly, the present results show that the lack of such a coupling did not preclude improvement of postinfarct function of myoblast-implanted hearts to the same extent as hearts transplanted with fetal cardiomyocytes. Likewise, the functional benefits of skeletal myoblasts 14 and fetal cardiomyocytes 3 have been reported in cryoinjury models in which implanted cells are insulated from the remaining myocardium by scar tissue and have therefore no possibility for establishing connections with host cardiomyocytes. This suggests that skeletal myoblasts could primarily be cardioprotective through their elastic properties, which would oppose the trend for postinfarct fibrous tissue to dilate over time. Because skeletal muscle tissue is formed both in the core and at the borders of the infarcted zone, cardiac, fibrotic, and skeletal tissues are intricated in vivo. The production of a muscle tissue of skeletal nature within the infarcted area, however, may change the physical properties of the scar and lead to a better compliance of the cardiac tissue, which could become more resistant to a progressive dilation. Thus transplanted cells would act as a tissue bandaging within the scar tissue. This hypothesis, which is consistent with our observations of limited remodeling in myoblast-implanted hearts, is also supported by the micromanometric and sonomicrometric findings that these cells are particularly effective in preserving postinfarct diastolic compliance. 18
In conclusion, transplantation of skeletal myoblasts limits postinfarct remodeling of the left ventricle and ultimately results in improved function. This improvement was similar in magnitude to that seen after implantation of fetal cardiomyocytes. Because skeletal myoblast transplantation would be easier to implement in clinical practice, it might thus find a place in the armamentarium of techniques designed to augment function of the failing heart.
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Appendix: Discussion |
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TopAbstractIntroductionMaterial and methods Results Discussion Appendix: Discussion References |
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Dr Scorsin. I did it before and, indeed, transplantation of cells results in an improvement of function, irrespective of whether the artery is reperfused or not.
Dr Juan C. Chachques (Paris, France). In the last 3 years of our work on an experimental model, we have implanted satellite cells (myoblasts) in small and big animals. We learned that mainly in the rat model it is necessary to correlate the echocardiographic studies with histologic studies because in many cases we do not find cells in the myocardium, even with an improvement in EF. Therefore I recommend that you correlate all your research in small animals with histologic studies of the myocardium because you can improve the EF by another mechanism that is not related to cell implantation. I think that the main conclusions in cellular cardiomyoplasty can be obtained by using big animals.
Dr Scorsin. Thank you for your remarks, Dr Chachques.
Dr Philippe Menasché (Paris, France). I would like to follow up briefly on Dr Allen’s question. Indeed, the first study that we did, now 5 years ago, was a study with ischemia and reperfusion. At that time, this was actually the first study we had done in showing that transplantation of cells did improve function to the same extent as it did in this particular study, where there was no reperfusion.
Regarding Dr Chachques’ comments, it should be noted that in all these animals, the improvement in function assessed by echocardiography was actually correlated with the presence of engrafted cells, which could be identified in all animals. This has also been shown by Doris Taylor by using a slightly different rabbit model, which shows a close correlation between engraftment of cells and improvement of function. Therefore we definitely believe that even if the mechanism by which cells improve function remains elusive, there is a clear correlation between the fact that cells are present in the tissue and the fact that function is improved.
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Footnotes |
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References |
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TopAbstractIntroductionMaterial and methods Results Discussion Appendix: Discussion References |
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|
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 G. H.L. Tang, P. W.M. Fedak, T. M. Yau, R. D. Weisel, A. Kulik, D. A.G. Mickle, and R.-K. Li Cell transplantation to improve ventricular function in the failing heart Eur. J. Cardiothorac. Surg., June 1, 2003; 23(6): 907 - 916. [Abstract] [Full Text] [PDF]
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P. Menasche Cell transplantation in myocardium Ann. Thorac. Surg., June 1, 2003; 75(90060): S20 - 28. [Abstract] [Full Text] [PDF]
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J. D. Dowell, M. Rubart, K. B.S. Pasumarthi, M. H. Soonpaa, and L. J. Field Myocyte and myogenic stem cell transplantation in the heart Cardiovasc Res, May 1, 2003; 58(2): 336 - 350. [Abstract] [Full Text] [PDF]
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P. Menasche Skeletal muscle satellite cell transplantation Cardiovasc Res, May 1, 2003; 58(2): 351 - 357. [Abstract] [Full Text] [PDF]
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T. Reffelmann and R. A. Kloner Cellular cardiomyoplasty--cardiomyocytes, skeletal myoblasts, or stem cells for regenerating myocardium and treatment of heart failure? Cardiovasc Res, May 1, 2003; 58(2): 358 - 368. [Full Text] [PDF]
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O. Agbulut, M.-L. Menot, Z. Li, F. Marotte, D. Paulin, A. A. Hagege, C. Chomienne, J.-L. Samuel, and P. Menasche Temporal patterns of bone marrow cell differentiation following transplantation in doxorubicin-induced cardiomyopathy Cardiovasc Res, May 1, 2003; 58(2): 451 - 459. [Abstract] [Full Text] [PDF]
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P. Menasche, A. A. Hagege, J.-T. Vilquin, M. Desnos, E. Abergel, B. Pouzet, A. Bel, S. Sarateanu, M. Scorsin, K. Schwartz, et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1078 - 1083. [Abstract] [Full Text] [PDF]
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E. Minami, H. Reinecke, and C. E. Murry Skeletal muscle meets cardiac muscle: Friends or foes? J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1084 - 1086. [Full Text] [PDF]
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N. Al Attar, C. Carrion, S. Ghostine, I. Garcin, J.-T. Vilquin, A. A. Hagege, and P. Menasche Long-term (1 year) functional and histological results of autologous skeletal muscle cells transplantation in rat Cardiovasc Res, April 1, 2003; 58(1): 142 - 148. [Abstract] [Full Text] [PDF]
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R. J. Hassink, A. Brutel de la Riviere, C. L. Mummery, and P. A. Doevendans Transplantation of cells for cardiac repair J. Am. Coll. Cardiol., March 5, 2003; 41(5): 711 - 717. [Abstract] [Full Text] [PDF]
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F. D. Pagani, H. DerSimonian, A. Zawadzka, K. Wetzel, A. S. B. Edge, D. B. Jacoby, J. H. Dinsmore, S. Wright, T. H. Aretz, H. J. Eisen, et al. Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans: Histological analysis of cell survival and differentiation J. Am. Coll. Cardiol., March 5, 2003; 41(5): 879 - 888. [Abstract] [Full Text] [PDF]
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R. D. Weisel, R.-K. Li, D. A. G. Mickle, and T. M. Yau Cell transplantation comes of age J. Thorac. Cardiovasc. Surg., March 1, 2003; 125(90030): S53 - 54. [Full Text] [PDF]
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T. M. Yau, S. Tomita, R. D. Weisel, Z.-Q. Jia, L. C. Tumiati, D. A.G. Mickle, and R.-K. Li Beneficial effect of autologous cell transplantation on infarcted heart function: comparison between bone marrow stromal cells and heart cells Ann. Thorac. Surg., January 1, 2003; 75(1): 169 - 177. [Abstract] [Full Text] [PDF]
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 M. Ruel, R. A. Kelly, and F. W. Sellke Therapeutic Angiogenesis, Transmyocardial Laser Revascularization, and Cell Therapy Card. Surg. Adult, January 1, 2003; 2(2003): 715 - 750. [Full Text]
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L. Gepstein Derivation and Potential Applications of Human Embryonic Stem Cells Circ. Res., November 15, 2002; 91(10): 866 - 876. [Abstract] [Full Text] [PDF]
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I. D. Cox, C. A. Thompson, and S. N. Oesterle Biointerventional cardiovascular therapy Eur. Heart J., November 2, 2002; 23(22): 1753 - 1756. [Full Text] [PDF]
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 A. BEHFAR, L. V. ZINGMAN, D. M. HODGSON, J.-M. RAUZIER, G. C. KANE, A. TERZIC, and M. PUCEAT Stem cell differentiation requires a paracrine pathway in the heart FASEB J, October 1, 2002; 16(12): 1558 - 1566. [Abstract] [Full Text] [PDF]
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S. Ghostine, C. Carrion, L. C. G. Souza, P. Richard, P. Bruneval, J.-T. Vilquin, B. Pouzet, K. Schwartz, P. Menasche, and A. A. Hagege Long-Term Efficacy of Myoblast Transplantation on Regional Structure and Function After Myocardial Infarction Circulation, September 24, 2002; 106(12_suppl_1): I-131 - I-136. [Abstract] [Full Text] [PDF]
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W.-H. Zimmermann, M. Didie, G. H. Wasmeier, U. Nixdorff, A. Hess, I. Melnychenko, O. Boy, W. L. Neuhuber, M. Weyand, and T. Eschenhagen Cardiac Grafting of Engineered Heart Tissue in Syngenic Rats Circulation, September 24, 2002; 106(12_suppl_1): I-151 - I-157. [Abstract] [Full Text] [PDF]
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Y. Sakakibara, K. Tambara, F. Lu, T. Nishina, G. Sakaguchi, N. Nagaya, K. Nishimura, R.-K. Li, R. D. Weisel, and M. Komeda Combined Procedure of Surgical Repair and Cell Transplantation for Left Ventricular Aneurysm: An Experimental Study Circulation, September 24, 2002; 106(12_suppl_1): I-193 - I-197. [Abstract] [Full Text] [PDF]
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Y. Sakakibara, K. Nishimura, K. Tambara, M. Yamamoto, F. Lu, Y. Tabata, and M. Komeda Prevascularization with gelatin microspheres containing basic fibroblast growth factor enhances the benefits of cardiomyocyte transplantation J. Thorac. Cardiovasc. Surg., July 1, 2002; 124(1): 50 - 56. [Abstract] [Full Text] [PDF]
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J. G. Shake, P. J. Gruber, W. A. Baumgartner, G. Senechal, J. Meyers, J. M. Redmond, M. F. Pittenger, and B. J. Martin Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects Ann. Thorac. Surg., June 1, 2002; 73(6): 1919 - 1926. [Abstract] [Full Text] [PDF]
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S. Tomita, D. A. G. Mickle, R. D. Weisel, Z.-Q. Jia, L. C. Tumiati, Y. Allidina, P. Liu, and R.-K. Li Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation J. Thorac. Cardiovasc. Surg., June 1, 2002; 123(6): 1132 - 1140. [Abstract] [Full Text] [PDF]
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W. Roell, Z. J. Lu, W. Bloch, S. Siedner, K. Tiemann, Y. Xia, E. Stoecker, M. Fleischmann, H. Bohlen, R. Stehle, et al. Cellular Cardiomyoplasty Improves Survival After Myocardial Injury Circulation, May 21, 2002; 105(20): 2435 - 2441. [Abstract] [Full Text] [PDF]
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 C. A Thompson and S. N Oesterle Biointerventional cardiology: the future interface of interventional cardiovascular medicine and bioengineering Vascular Medicine, May 1, 2002; 7(2): 135 - 140. [Abstract] [PDF]
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K. Suzuki, B. Murtuza, L. Heslop, J. E. Morgan, R. T. Smolenski, N. Suzuki, T. A. Partridge, and M. H. Yacoub Single fibers of skeletal muscle as a novel graft for cell transplantation to the heart J. Thorac. Cardiovasc. Surg., May 1, 2002; 123(5): 984 - 992. [Abstract] [Full Text] [PDF]
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P Menasche and M Desnos Cardiac reparation: fixing the heart with cells, new vessels and genes Eur. Heart J. Suppl., April 1, 2002; 4(suppl_D): D73 - D81. [Abstract] [PDF]
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M. Takagaki, P. M. McCarthy, T. Tabata, R. Dessoffy, L. A. Cardon, J. Connor, Y. Ochiai, J. D. Thomas, G. S. Francis, J. B. Young, et al. Induction and maintenance of an experimental model of severe cardiomyopathy with a novel protocol of rapid ventricular pacing J. Thorac. Cardiovasc. Surg., March 1, 2002; 123(3): 544 - 549. [Abstract] [Full Text] [PDF]
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W.-H. Zimmermann, K. Schneiderbanger, P. Schubert, M. Didie, F. Munzel, J.F. Heubach, S. Kostin, W.L. Neuhuber, and T. Eschenhagen Tissue Engineering of a Differentiated Cardiac Muscle Construct Circ. Res., February 8, 2002; 90(2): 223 - 230. [Abstract] [Full Text] [PDF]
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 C.E. MURRY, M.L. WHITNEY, M.A. LAFLAMME, H. REINECKE, and L.J. FIELD Cellular Therapies for Myocardial Infarct Repair Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 519 - 526. [Abstract] [PDF]
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 A. A. Hagege, J.-T. Vilquin, P. Bruneval, and P. Menasche Regeneration of the Myocardium: A New Role in the Treatment of Ischemic Heart Disease? Hypertension, December 1, 2001; 38(6): 1413 - 1415. [Abstract] [Full Text] [PDF]
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K. Suzuki, B. Murtuza, R. T. Smolenski, I. A. Sammut, N. Suzuki, Y. Kaneda, and M. H. Yacoub Cell Transplantation for the Treatment of Acute Myocardial Infarction Using Vascular Endothelial Growth Factor-Expressing Skeletal Myoblasts Circulation, September 18, 2001; 104 (2009): I-207 - I-212. [Abstract] [Full Text] [PDF]
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K. Suzuki, B. Murtuza, N. Suzuki, R. T. Smolenski, and M. H. Yacoub Intracoronary Infusion of Skeletal Myoblasts Improves Cardiac Function in Doxorubicin-Induced Heart Failure Circulation, September 18, 2001; 104 (2009): I-213 - I-217. [Abstract] [Full Text] [PDF]
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T. M. Yau, K. Fung, R. D. Weisel, T. Fujii, D. A.G. Mickle, and R.-K. Li Enhanced Myocardial Angiogenesis by Gene Transfer With Transplanted Cells Circulation, September 18, 2001; 104 (2009): I-218 - I-222. [Abstract] [Full Text] [PDF]
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B. Pouzet, S. Ghostine, J.-T. Vilquin, I. Garcin, M. Scorsin, A. A. Hagege, D. Duboc, K. Schwartz, and P. Menasche Is Skeletal Myoblast Transplantation Clinically Relevant in the Era of Angiotensin-Converting Enzyme Inhibitors? Circulation, September 18, 2001; 104 (2009): I-223 - I-228. [Abstract] [Full Text] [PDF]
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R. D. Weisel, R.-K. Li, D. A.G. Mickle, and T. M. Yau Cell transplantation comes of age J. Thorac. Cardiovasc. Surg., May 1, 2001; 121(5): 835 - 836. [Full Text] [PDF]
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C. Rajnoch, J.-C. Chachques, A. Berrebi, P. Bruneval, M.-O. Benoit, and A. Carpentier Cellular therapy reverses myocardial dysfunction J. Thorac. Cardiovasc. Surg., May 1, 2001; 121(5): 871 - 878. [Abstract] [Full Text] [PDF]
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B. Pouzet, J.-T. Vilquin, A. A. Hagege, M. Scorsin, E. Messas, M. Fiszman, K. Schwartz, and P. Menasche Factors affecting functional outcome after autologous skeletal myoblast transplantation Ann. Thorac. Surg., March 1, 2001; 71(3): 844 - 851. [Abstract] [Full Text] [PDF]
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 A. A HAGÈGE and P. MENASCHÉ Cellular cardiomyoplasty: a new hope in heart failure? Heart, November 1, 2000; 84(5): 465 - 466. [Full Text]
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W.-H. Zimmermann, K. Schneiderbanger, P. Schubert, M. Didie, F. Munzel, J.F. Heubach, S. Kostin, W.L. Neuhuber, and T. Eschenhagen Tissue Engineering of a Differentiated Cardiac Muscle Construct Circ. Res., February 8, 2002; 90(2): 223 - 230. [Abstract] [Full Text] [PDF]
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