Download or read book Cardiac Repair Using Stem Cells Conditioned Media Based Therapy in a Rodent Model of Myocardial Infarction and Heart Failure written by Mohammad Alrefai and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "ABSTRACT Objectives: Myocardial infarction (MI) is the most common cause of congestive heart failure (CHF). Both diseases are associated with significant morbidity and mortality. Cell-based therapy has demonstrated variable degrees of success in the treatment of myocardial infarction and heart failure. Recently, a major advancement in the stem cell field has been made after the introduction of human induced pluripotent stem cells (HiPSCs) as it carried the advantage of non-invasive harvesting methods over the other types of cell based therapy. Here, we investigated the effects of conditioned media (CM) of HiPSCs and mesenchymal stem cells (MSC) on the cardiac function and remodeling of experimental MI and CHF rat model. It was hypothesized that signaling molecules VEGF and PDGF present in cell conditioning media would have angiogenesis and neovascularization properties to induce improvement in myocardial function and reduction in scar size after MI. Methods: In-vitro preparations: HiPSCs and MSCs were cultured in DMEM containing 5% pluripotent stem cell growth supplement and DMEM alone, respectively. Cells were incubated for 24 hours in the conditioning medium in CO2 chamber at 37C°, thereafter conditioning media was collected and stored in -80C° for further use. In-vivo preparations: A total of 30 female Lewis rats underwent surgical ligation of the left anterior descending coronary artery through a left thoracotomy. Animals were randomized (n=10/group) to receive one of three treatments injected into the peri-infarct area; normal saline (NS), HiPSC (HiPSC CM) and MSC (MSC CM). Group NS, received (500 [mu]L) of normal saline, group HiPSC and MSC received intramyocardial injection of HiPSCs-CM (500 [mu]L) or MSC-CM, respectively injected into the peri-infarcted zone 15 minutes after the ligation. Left ventricular ejection fraction (LVEF), fractional shortening (FS), histology was evaluated in a blinded fashion, at pre-op day 0 then at 1, 2, 4 and 6 weeks and serum proteomics were evaluated at 2 weeks. Results: Echocardiography showed a significant improvement of EF and FS in both group HiPSC and MSC compared to group NS (P

Download or read book Stem Cells and Myocardial Regeneration written by Marc S. Penn and published by Springer Science & Business Media. This book was released on 2007-11-06 with total page 314 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the past 5 years there has been great excitement and controversy in the scientific, financial, and lay literature for the potential of stem cell-based strategies for the prev- tion and treatment of chronic heart failure (CHF). Not that long ago we believed we were born with a set number of cardiac myocytes and that once damaged there was no hope to replace them. The interest in the field stems from the magnitude of cardiovascular disease in the world. Our ability to treat and help patients survive acute myocardial infarction (MI) has resulted in a near epidemic of CHF. There are more than 5 million Americans who currently carry the diagnosis of CHF. With more than 1 million MIs a year in the United States, there are approx 500,000 new cases of CHF diagnosed each year. The goal of Stem Cells and Myocardial Regeneration is to present, in a coherent manner, the current state of knowledge of stem cell-based therapies for cardiac dysfunction, including current findings in both the laboratory and the clinic trials. The first section of this Stem Cells and Myocardial Regeneration focuses on the magnitude of the problem and the successes and failures of what we consider optimal medical therapy. It is on this background that stem cell-based therapy needs to build.

Download or read book Stem Cell Therapy and Tissue Engineering for Cardiovascular Repair written by Nabil Dib and published by Springer Science & Business Media. This book was released on 2006-04-09 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: In excess of 7 million people worldwide die of coronary heart disease each year. Only one-third of these heart attack victims recover completely. The remainder suffer the consequences of myocardial infarction and its ill fated remodeling process, resulting in chronic congestive heart failure. This malady alone is the leading cause of hospital admissions in the United States. New breakthroughs in stem cell therapy and tissue engineering have promised to reverse this dismal outcome by cardiovascular repair. World authorities, including scientists and regulatory authorities, have joined in a collaborative effort to present for the reader the first collective review of stem cell therapy for the treatment of cardiovascular disease. These contributions in basic science, pre-clinical and clinical experience guided by the regulatory pathways, assure a rapid course of translational research and clinical trials. The contents of this publication will become a prerequisite for those preparing to meet the challenges of this exciting and potentially rewarding field of stem cell research.

Download or read book Cardiac Regeneration written by Masaki Ieda and published by Springer. This book was released on 2017-10-27 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Volume of the series Cardiac and Vascular Biology offers a comprehensive and exciting, state-of-the-art work on the current options and potentials of cardiac regeneration and repair. Several techniques and approaches have been developed for heart failure repair: direct injection of cells, programming of scar tissue into functional myocardium, and tissue-engineered heart muscle support. The book introduces the rationale for these different approaches in cell-based heart regeneration and discusses the most important considerations for clinical translation. Expert authors discuss when, why, and how heart muscle can be salvaged. The book represents a valuable resource for stem cell researchers, cardiologists, bioengineers, and biomedical scientists studying cardiac function and regeneration.

Download or read book Heart Regeneration written by Felix B. Engel and published by World Scientific. This book was released on 2012 with total page 393 pages. Available in PDF, EPUB and Kindle. Book excerpt: This title presents the major advances of the last decade in the field of cardiac regeneration.

Download or read book Cardiovascular Regeneration and Stem Cell Therapy written by Annarosa Leri and published by John Wiley & Sons. This book was released on 2008-04-15 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is the definitive reference on two of the most exciting areas of cardiovascular research – myocardial regeneration and stem cell therapy – for the treatment of disease. Edited by pioneers in the area, with contributions from every major investigator worldwide, it covers: The biology of stem cells The actions of stem cells from the bone marrow, the heart, and embryos on the normal restorative and repair functions of the heart and blood vessels How stem cells could contribute to myocardial recovery in the face of injury and aging How adjuvant therapy with growth factors might enhance stem cell activity in regeneration and repair Clinical applications and clinical experiences This fully referenced publication presents the current state of knowledge in both basic science and clinical practice, and is an essential reference for scientists, students, and clinicians.

Download or read book Stem Cell Therapy for Myocardial Repair written by Julia M. Feygin and published by . This book was released on 2007 with total page 388 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Handbook of Cardiac Stem Cell Therapy written by Ioannis Dimarakis and published by World Scientific. This book was released on 2009 with total page 306 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is an impressive compilation of contributions on the hot topic of cardiac stem cell therapy from leading groups all over the world. In the assembly of chapters, a structured approach is adopted; starting from the clinician's perspective, all developments in both the experimental and clinical research areas are covered. This journey will take the reader from the bench-top to the bedside, with all chapters written by leading authorities in their respective fields, including data still in press with medical journals. So, beyond being excellent as an overall update for scientists in the field of cardiac stem cell therapy, this book will likely prove an indispensable tool for every budding scientist considering a research project within this field.

Download or read book Enhancing Myocardial Repair with CardioClusters written by Megan Michele Mendes Monsanto and published by . This book was released on 2020 with total page 167 pages. Available in PDF, EPUB and Kindle. Book excerpt: Heart disease leading to cardiovascular failure is a major public health issue in the United States with a considerable burden for the health care system. Despite recent progress to advance stem cell-based therapy for patients, heart failure carries a five-year mortality that rivals most cancers. This proposal describes an approach to control and pattern three distinct stem cell populations derived from the human heart to promote superior repair and regeneration after myocardial infarction. Regenerative capacity of the heart is mediated through multiple distinct populations of stem cell types that are the subject of ongoing intense study. In the past decade, isolation and characterization of c-kit+ cardiac progenitor cells (CPCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) have provided substantial insight to the capabilities of stem cells to rebuild the damaged heart and advance clinical therapy. Clinical trials have proven the efficacy and safety of autologous and allogeneic cell delivery to human patients, yet improvements in cardiac function and reduction in scar tissue remain modest and far below that needed for restoration of normal functional output. The work presented in this dissertation project overcomes these current cell-based limitations by using a novel method for improving myocardial repair: CardioClusters, a three-dimensional microenvironment consisting of CPCs, MSCs and EPCs. The innovation of this project is the creation of CardioClusters with the ability to capitalize upon beneficial attributes of multiple human stem cells from a single human heart providing a clinically relevant translational strategy. Collectively, studies in this dissertation will pave the way for interventional approaches to selectively adapt stem cell behavior and merge beneficial attributes of stem cell populations found within the human heart for prevention of heart failure after cardiomyopathic injury.

Download or read book Cardiac Regeneration using Stem Cells written by Keiichi Fukuda and published by CRC Press. This book was released on 2013-04-10 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt: To achieve cardiac regeneration using pluripotent stem (iPS) cells, researchers must understand iPS cell generation methods, cardiomyocyte differentiation protocols, cardiomyocyte characterization methods, and tissue engineering. This book presents the current status and future possibilities in cardiac regeneration using iPS cells. Written by top researchers who present new data in these fields, this book reviews cardiac cell therapy for ischemic heart disease and explores in vitro generation of efficacious platelets from iPS cells. It also discusses modeling arrhythmogenic heart disease with patient-specific induced pluripotent stem cells.

Download or read book An Essential Guide to Cardiac Cell Therapy written by Emerson Perin and published by CRC Press. This book was released on 2006-09-15 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt: Sparked by a new understanding that the development of tissues is not restricted to the embryonic phase of development and thus that regeneration of tissues can occur in adults, the emerging field of stem cell therapy has grown exponentially in the last several years. Crucially, the research and findings associated with stem cell research overlap into many other areas, such as basic cell biology, molecular biology and hematology, and the proliferation of clinical studies involving stem cell research is gradually crossing over into the practice of medicine as many patients may become candidates for such novel treatments. As a response to this, Guide to Cardiac Cell Therapy is a comprehensive but understandable resource that makes this exciting field accessible to clinical practitioners. Bridging the gap between basic science and practice, it is a useful introduction to the area as well as a cutting-edge update of the developments in stem cell therapy as applied to cardiovascular disease.

Download or read book Cardiac Regeneration and Repair written by Ren-Ke Li and published by Elsevier. This book was released on 2014-02-17 with total page 509 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiac Regeneration and Repair, Volume Two reviews the use of biomaterials, alone or combined with cell therapy, in providing tissue-engineered constructs to repair the injured heart and prevent or reverse heart failure. Part one explores the variety of biomaterials available for cardiac repair, including nanomaterials and hydrogels. Further chapters explore the use of biomaterials to enhance stem cell therapy for restoring ventricular function and generating stem cell-modified intravascular stents. Part two focuses on tissue engineering for cardiac repair, including chapters on decellularized biologic scaffolds, synthetic scaffolds, cell sheet engineering, maturation of functional cardiac tissue patches, vascularized engineered tissues for in vivo and in vitro applications, and clinical considerations for cardiac tissue engineering. Finally, part three explores vascular remodeling, including chapters highlighting aortic extracellular matrix remodeling, cell-biomaterial interactions for blood vessel formation, and stem cells for tissue-engineered blood vessels. Cardiac Regeneration and Repair, Volume Two is complemented by an initial volume covering pathology and therapies. Together, the two volumes of Cardiac Regeneration and Repair provide a comprehensive resource for clinicians, scientists, or academicians fascinated with cardiac regeneration, including those interested in cell therapy, tissue engineering, or biomaterials. Surveys the variety of biomaterials available for cardiac repair, including nanomaterials and hydrogels. Focuses on tissue engineering for cardiac repair including clinical considerations for cardiac tissue engineering Explores vascular remodeling, highlighting aortic extracellular matrix remodeling, cell-biomaterial interactions for blood vessel formation, and stem cells for tissue-engineered blood vessels

Download or read book Conditioning of Mesenchymal Stem Cells Initiates Cardiogenic Differentiation and Increases Function in Infarcted Hearts written by Jacques Paul Guyette and published by . This book was released on 2012 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Current treatment options are limited for patients with myocardial infarction or heart failure. Cellular cardiomyoplasty is a promising therapeutic strategy being investigated as a potential treatment, which aims to deliver exogenous cells to the infarcted heart, for the purpose of restoring healthy myocardial mass and mechanical cardiac function. While several cell types have been studied for this application, only bone marrow cells and human mesenchymal stem cells (hMSCs) have been shown to be safe and effective for improving cardiac function in clinical trials. In both human and animal studies, the delivery of hMSCs to infarcted myocardium decreased inflammatory response, promoted cardiomyocyte survival, and improved cardiac functional indices. While the benefits of using hMSCs as a cell therapy for cardiac repair are encouraging, the desired expectation of cardiomyoplasty is to increase cardiomyocyte content that will contribute to active cardiac mechanical function. Delivered cells may increase myocyte content by several different mechanisms such as differentiating to a cardiomyocyte lineage, secreting paracrine factors that increase native stem cell differentiation, or secreting factors that increase native myocyte proliferation. Considerable work suggests that hMSCs can differentiate towards a cardiomyocyte lineage based on measured milestones such as cardiac-specific marker expression, sarcomere formation, ion current propagation, and gap junction formation. However, current methods for cardiac differentiation of hMSCs have significant limitations. Current differentiation techniques are complicated and tedious, signaling pathways and mechanisms are largely unknown, and only a small percentage of hMSCs appear to exhibit cardiogenic traits. In this body of work, we developed a simple strategy to initiate cardiac differentiation of hMSCs in vitro. Incorporating environmental cues typically found in a myocardial infarct (e.g. decreased oxygen tension and increased concentrations of cell-signaling factors), our novel in vitro conditioning regimen combines reduced-O2 culture and hepatocyte growth factor (HGF) treatment. Reduced-O2 culturing of hMSCs has shown to enhance differentiation, tissue formation, and the release of cardioprotective signaling factors. HGF is a pleiotropic cytokine involved in several biological processes including developmental cardiomyogenesis, through its interaction with the tyrosine kinase receptor c-Met. We hypothesize that applying a combined conditioning treatment of reduced-O2 and HGF to hMSCs in vitro will enhance cardiac-specific gene and protein expression. Additionally, the transplantation of conditioned hMSCs into an in vivo infarct model will result in differentiation of delivered hMSCs and improved cardiac mechanical function. In testing our hypothesis, we show that reduced-O2 culturing can enhance hMSC growth kinetics and total c-Met expression. Combining reduced-O2 culturing with HGF treatment, hMSCs can be conditioned to express cardiac-specific genes and proteins in vitro. Using small-molecule inhibitors to target specific effector proteins in a proposed HGF/c-Met signaling pathway, treated reduced-O2/HGF hMSCs show a decrease in cardiac gene expression. When implanted into rat infarcts in vivo, reduced-O2/HGF conditioned hMSCs increase regional cardiac mechanics within the infarct region at 1 week and 1 month. Further analysis from the in vivo study showed a significant increase in the retention of reduced-O2/HGF conditioned hMSCs. Immunohistochemistry showed that some of the reduced-O2/HGF conditioned hMSCs express cardiac-specific proteins in vivo. These results suggest that a combined regimen of reduced-O2 and HGF conditioning increases cardiac-specific marker expression in hMSCs in vitro. In addition, the implantation of reduced-O2/HGF conditioned hMSCs into an infarct significantly improves cardiac function, with contributing factors of improved cell retention and possible increases in myocyte content. Overall, we developed a simple in vitro conditioning regimen to improve cardiac differentiation capabilities in hMSCs, in order to enhance the outcomes of using hMSCs as a cell therapy for the diseased heart.

Download or read book Cardiac Tissue Engineering written by Milica Radisic and published by Humana Press. This book was released on 2014-07-29 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiac Tissue Engineering: Methods and Protocols presents a collection of protocols on cardiac tissue engineering from pioneering and leading researchers around the globe. These include methods and protocols for cell preparation, biomaterial preparation, cell seeding, and cultivation in various systems. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Cardiac Tissue Engineering: Methods and Protocols highlights the major techniques, both experimental and computational, for the study of cardiovascular tissue engineering.

Download or read book Gene Therapy and Cell Fusion Enhances Stem Cell Mediated Cardiac Repair written by Pearl Jennine Quijada and published by . This book was released on 2015 with total page 130 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiovascular disease is the leading cause of mortality in the United States. Myocardial infarction (MI) induces massive cellular death and leads to a decline in cardiac function. Cardiomyocytes have limited proliferative capacity sparking interests in molecular and cellular strategies to promote stem cell conversion into new cardiomyocytes. Cardiac progenitor cells (CPCs) are tissue resident stem cells that give rise to cardiomyogenic structures. Although, CPCs introduced into the heart confer improvements in cardiac function after MI, these effects are not sufficient to support complete heart regeneration and prevent heart failure. Studying molecular pathways that contribute to CPC survival and commitment is essential in advancing CPC based therapeutic approaches. Ca2+/Calmodulin-dependent protein kinase II[Delta]B (CaMKII[Delta]B) regulates survival and growth in cardiomyocytes. However, the role of CaMKII[Delta] in CPCs has not been previously explored. CPCs increase nuclear CaMKII after MI and in vitro differentiation suggesting that CaMKII[Delta]B contributes to the regulation of CPC commitment. Overexpression of CaMKII[Delta]B in CPCs reduces proliferation, enhances resistance to death and increases cardiac specific differentiation. CaMKII[Delta]B may serve as a novel modulatory kinase to promote CPC survival and commitment. Despite increasing use of stem cells for regenerative-based cardiac therapy, the optimal stem cell population(s) remains uncertain. In the past decade there has been increasing interest and characterization of stem cell populations reported to directly and/or indirectly contributes to cardiac regeneration through processes of cardiomyogenic commitment and / or release of cardioprotective paracrine factors. Future therapies require development of unprecedented concepts to enhance myocardial healing. Combinatorial cell therapy utilizing CPCs and bone marrow derived mesenchymal stem cells (MSCs) promote enhanced reparative functions in vivo. However, identifying cell specific mechanisms of cardiac repair are difficult using dual cell systems. Here, we performed cell fusion between CPCs and MSCs to obtain hybrids with combined cell characteristics called CardioChimeras. Our ideal cell therapy is to combine the beneficial properties of CPCs to undergo cardiac specific commitment as well as MSCs that foster an improved microenvironment with protective paracrine secretion.

Download or read book Mesenchymal Stem Cell Therapy written by Lucas G. Chase and published by Springer Science & Business Media. This book was released on 2012-12-12 with total page 458 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the past decade, significant efforts have been made to develop stem cell-based therapies for difficult to treat diseases. Multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), appear to hold great promise in regards to a regenerative cell-based therapy for the treatment of these diseases. Currently, more than 200 clinical trials are underway worldwide exploring the use of MSCs for the treatment of a wide range of disorders including bone, cartilage and tendon damage, myocardial infarction, graft-versus-host disease, Crohn’s disease, diabetes, multiple sclerosis, critical limb ischemia and many others. MSCs were first identified by Friendenstein and colleagues as an adherent stromal cell population within the bone marrow with the ability to form clonogenic colonies in vitro. In regards to the basic biology associated with MSCs, there has been tremendous progress towards understanding this cell population’s phenotype and function from a range of tissue sources. Despite enormous progress and an overall increased understanding of MSCs at the molecular and cellular level, several critical questions remain to be answered in regards to the use of these cells in therapeutic applications. Clinically, both autologous and allogenic approaches for the transplantation of MSCs are being explored. Several of the processing steps needed for the clinical application of MSCs, including isolation from various tissues, scalable in vitro expansion, cell banking, dose preparation, quality control parameters, delivery methods and numerous others are being extensively studied. Despite a significant number of ongoing clinical trials, none of the current therapeutic approaches have, at this point, become a standard of care treatment. Although exceptionally promising, the clinical translation of MSC-based therapies is still a work in progress. The extensive number of ongoing clinical trials is expected to provide a clearer path forward for the realization and implementation of MSCs in regenerative medicine. Towards this end, reviews of current clinical trial results and discussions of relevant topics association with the clinical application of MSCs are compiled in this book from some of the leading researchers in this exciting and rapidly advancing field. Although not absolutely all-inclusive, we hope the chapters within this book can promote and enable a better understanding of the translation of MSCs from bench-to-bedside and inspire researchers to further explore this promising and quickly evolving field.

Download or read book Mesenchymal Stem Cells Derived from Pluripotent Stem Cells for Cardiovascular Repair and Regeneration written by Yuelin Zhang and published by Open Dissertation Press. This book was released on 2017-01-26 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Mesenchymal Stem Cells Derived From Pluripotent Stem Cells for Cardiovascular Repair and Regeneration" by Yuelin, Zhang, 張月林, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Despite major advances in pharmacological and surgical treatments of cardiovascular diseases (CVDs), clinical outcomes of patients with severe CVDs remain very poor. Most of medication and interventions currently available are only playing roles of preventing further damage to myocardium, declining the risk of on-going cardiovascular events, lifting the cardiac pumping efficiency and lower early mortality rates, none of these treatments can regenerate or repair damaged cardiac tissue or restore heart function. As a result, several new strategies have been explored to overcome limitations of current therapeutic approaches. One prospective is to replace dead cardiac vascular cells with young and green cells to repair or regenerate damaged heart myocardium. Several types of stem cells, including bone marrow hematopoietic stem cells, mesenchymal stem cells (MSCs), embryonic stem cell (ESCs)and induced pluripotent stem cells (iPSCs), have been tested as the candidates for treatment of CVDs. Among a myriad of types of stem cells, bone marrow derived MSCs(BM-MSCs) has received great attention based on several unique properties such as easy isolation and expansion, stable genetic background and low immunogenicity. However, the therapeutic efficacy of BM-MSCs derived from aging or diseased donors is impaired. The differentiation potential of BM-MSCs is gradually reduced with the increased culture time. Thus, it is urgent to identify some novel alternative sources for MSCs. Moreover, the potential mechanisms of MSCs therapy have not been understood totally. This thesis is designed to investigate the therapeutic efficacy and potential mechanisms of several novel types of MSCs, including hESC-MSCs and hiPSC-MSCs and Rap1-/--BM-MSCson several types of CVDs, including pulmonary arterial hypertension (PAH), dilated cardiomyopathy (DCM)and myocardial infarction (MI). In Chapter 4, it disclosed that hESC-MSCs have a better therapeutic efficacy than BM-MSCs in attenuation of PAH induced by monocrotaline in mice. The greater therapeutic potential of hESC-MSCs on PAH was not only attributed to the higher capacity of differentiation into de-novo vascular cells, but also attributed to higher cell survival rate and greater paracrine effects post-transplantation. In Chapter 5, it demonstrated that compared with BM-MSCs, iPSC-MSCs have a better therapeutic effect on doxorubicin-induced cardiomyopathy. Several potential mechanisms of action were involved in iPSC-MSCs-based therapy for cardiomyopathy. It demonstrated that iPSC-MSCs transplantation not only attenuated the generation of reactive oxygen species(ROS)and the level of inflammation, but also restored depletion of cardiac progenitor cells and promoted endogenous myocardial regeneration against doxorubicin induced cardiomyopathy. Moreover, mitochondrial transfer and paracrine actions of iPSC-MSCs played critical roles in the rescue for doxorubicin-induced cardiomyopathy. In Chapter 6, it uncovered that compared with wild type BM-MSCs, Rap1-/--BM-MSCs transplantation achieved a better benefit to MI induced by ligation of left anterior descending (LAD)coronary artery. Rap1-mediated NF-κB activity plays a key role in regulation MSCscytokine secretion profiles. The absence of Rap1 in MSCs leads to reduced pro-inflammatory cytokines secretion and enhanced MSCs survival capacity, thus yielding a better therapeut