Stem cells to repair the broken heart: much ado about nothing? (original) (raw)
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Stem cell therapy in acute myocardial infarction: A pot of gold or Pandora's box
2011
Stem cell therapy for conditions characterized by myocyte loss in myocardial infarction and heart failure is intuitively appealing. Stem cells from various sources, including heart itself in preclinical and animal studies, have shown the potential to improve the function of ventricular muscle after ischaemic injury. The clinical experience from worldwide studies have indicated the safety profile but with modest benefits. The predominant mechanisms of transplanted cells for improving cardiac function have pointed towards paracrine effects rather than transdifferentiation into cardiomyocytes. Thus, further investigations should be encouraged towards bench side and bedside to resolve various issues for ensuring the correct type and dosing of cells, time, and method of delivery and identify correct mechanism of functional improvement. An interdisciplinary effort at the scientific, clinical, and the government front will bring successful realization of this therapy for healing the heart and may convert what seems now a Pandora's Box into a Pot of Gold.
Stem cells for myocardial repair
Thrombosis & Haemostasis, 2010
There is a growing interest in the clinical application for stem cell as a novel therapy for treatment of acute myocardial infarction and chronic myocardial ischaemia. The initial premise is the transplanted exogenous stem cells can engraft and integrate with host myocardium for cardiac regeneration. However, recent experimental studies suggest that multiple mechanisms, including remodelling of extracellular matrix, enhancement of neovascularisation and recruitment of endogenous stem cells are more likely to contribute to the beneficial effects of stem cell therapy that direct trans-differentiation of stem cells into functional myocardium. Among different potential cell sources, bone marrow-derived cells and skeletal myoblasts have been tested in pilot clinical trials. Phase I/II randomised controlled clinical trials suggest that intracoronary or intramyocardial injection of bone marrow-derived cells may be safe and feasible strategies for treatment of acute myocardial infarction as well as chronic myocardial ischaemia. In addition, these studies show a modest, but significant improvement in left ventricular ejection fraction and clinical status of patients after cell transplantation. Nevertheless, most of these studies included a relatively small sample size (<200) and short duration of follow-up (<6 months), and the clinical efficacy of stem cell therapy need to be confirmed by future clinical trials. Furthermore, the optimal timing, cell types and mode of delivery need to be addressed, and strategies to improve cell survival and engraftment should also be developed to overcome the potential hurdles related to cell-based therapy.
European Journal of Heart Failure, 2005
Background: Transplantation of bone marrow derived adult stem cells (BMC) improves cardiac function after acute myocardial infarction (MI). However, the cell population mediating myocardial recovery and the fate of the transplanted cells are still controversial. Aims: We determined the effects of Sca-1 + c-kit + lin À haematopoietic BMC on cardiac function after MI and the cell fate after transplantation. Methods: Sca-1 + c-kit + lin À BMC of male donor C57BL/6 mice were transplanted by intravenous injection into syngenic females after permanent MI. LV dimensions and function were determined by echocardiography and cardiac magnetic resonance imaging, transplanted BMC were identified by Y chromosome DNA in situ hybridization. Results: BMC treatment completely prevented LV dilation (LV enddiastolic volume BMC 70 T 16 Al vs. control 122 T 41 Al; p < 0.05) and improved fractional shortening (BMC 22.9 T 8% vs. control 15.4 T 8.4%; p < 0.05) and ejection fraction (BMC 68.2 T 6.6% vs. control 52 T 14.3%, p < 0.05) as early as 3 days after transplantation, but did not decrease infarct size (BMC 27 T 6% vs. control 28 T 7%, p = n.s.). After 4 weeks, only sporadic cells of male origin were identified in infarcted hearts (<0.01% of periinfarct cells). Conclusion: Intravenous injection of sca-1 + c-kit + lin À BMC after MI improves LV dimensions and function without evidence for long term engraftment.
Stem cells for cardiac repair in acute myocardial infarction
Expert Review of Cardiovascular Therapy, 2011
Despite recent advances in medical therapy, reperfusion strategies, implantable cardio verterdefibrillators and cardiac assist devices, ischemic heart disease is a frequent cause of morbidity and mortality worldwide. Cell therapy has been introduced as a new treatment modality to regenerate lost cardiomyocytes. At present, several cell types seem to improve left ventricular function in animal models as well as in humans, but evidence for true generation of new myocardium is confined to the experimental models. In the clinical perspective, myocardial regeneration has been replaced by myocardial repair, as other mechanisms seem to be involved. Clinical studies on adult stem cells suggest, at best, moderate beneficial effects on surrogate end points, but some applications may qualify for evaluation in larger trials. Complete regeneration of the myocardium by cell therapy after a large myocardial infarction is still visionary, but pluripotent stem cells and tissue engineering are important tools to solve the puzzle.
Stem cells for myocardial infarction: an update
Biotecnologia Aplicada
Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new treatments. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials. The recent breakthroughs in stem cell studies, molecular and cell biology, and tissue engineering have prepared the route for developing a new biomedical discipline: regenerative medicine. In the field of cardiovascular medicine, the real promise of a stem cell-based regeneration and repair lies in the promotion of myogenesis at the site of the cell graft and in the development of angiogenesis processes to achieve both structural and functional benefits. This review critically discusses the recent findings in the field of stem cells and their use in the treatment of vascular diseases. Here we analyze the sources of cells available for therapy in cardiovascular diseases. We also propose the mechanisms by which stem cells can promote angiogenesis and functional improvement. Finally we discuss the most recent results in pre-clinical experimentation and clinical trials regarding myocardial infarction.
Stem Cell Therapy for Myocardial Infarction: Challenges and Prospects
Abstract Myocardial infarction causes death worldwide with the greatest incidence being in the United States. Although there have been many advances in myocardial re-perfusion strategies and novel pharmacological approaches, therapies for treating acute and chronic myocardial ischemic damage remain limited. This means that no currently available heart failure treatment has demonstrated an ability to generate new muscle tissue within the scared regions of the heart. Stem cell, however, offers new hope to patients who have otherwise limited choices. Therefore, this review aims at exploring the use and peculiarities of stem cell therapy for myocardial infarction. But the success of stem cell therapy for clinical use needs the validation of several issues ranging from selection of appropriate stem cells, routes of transfer, establishment of conducive trans-differentiation milieu with associated cytokines, means to evaluate/track response to cell therapy to compliance with regulatory and ethical issues besides addressing biological and technical issues surrounding stem cell therapy.