Cardiomyocyte Transplantation in a Porcine Myocardial Infarction Model

Watanabe, Eiichi; Smith, Duane M.; Delcarpio, Joseph B.; Sun, Jun; Smart, Frank W.; Meter, Clifford H. Van; Claycomb, William C.

doi:10.1016/s0963-6897(98)00011-6

Cited by 97 publications

(51 citation statements)

References 25 publications

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“…Cell implantation utilizing cardiac stem cells [18], embryonic stem cells [19], hematopoietic stem cells [20], MSCs [21][22][23], skeletal myoblasts [24][25][26], and cardiac myocytes (adult, fetal, or neonatal myocytes) [27,28] has been suggested to be a promising clinical approach for restoration of myocardial function after cardiac infarction. Among these various candidate cell types, MSCs have a great advantage with respect to generating functional cardiac myocytes in the infarcted myocardium because of their ease of preparation and potential to differentiate into a cardiac lineage [29,30] both in vivo and in vitro under appropriate culture conditions.…”

Section: Discussionmentioning

confidence: 99%

Integrin-Linked Kinase Is Required in Hypoxic Mesenchymal Stem Cells for Strengthening Cell Adhesion to Ischemic Myocardium

et al. 2009

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Mesenchymal stem cells (MSCs) therapy has limitations due to the poor viability of MSCs after cell transplantation. Integrin-mediated adhesion is a prerequisite for cell survival. As a novel anti-death strategy to improve cell survival in the infarcted heart, MSCs were genetically modified to overexpress integrin-linked kinase (ILK). The survival rate of ILK-transfected MSCs (ILK-MSCs) was augmented by about 1.5-fold and the phosphorylation of ERK1/2 and Akt in ILK-MSCs were increased by about three and twofold, respectively. ILK-MSCs demonstrated an increase of twofold in the ratio of Bcl-2/Bax and inhibited caspase-3 activation, compared with hypoxic MSCs. The adhesion rate of ILK-MSCs also had a 32.2% increase on the cardiac fibroblast-derived three-dimensional matrix and ILK-MSCs showed higher retention by about fourfold compared to unmodified MSCs. Six animals per group were used for the in vivo experiments analyzed at 1 week after occlusion of the left coronary artery. ILK-MSC transplanted rats had a 12.0% 6 3.1% smaller infarct size than MSC-treated rats after ligation of left anterior descending coronary artery. Transplantation of ILK-MSCs not only led to a 16.0% 6 0.4% decrease in the fibrotic heart area, but also significantly reduced the apoptotic positive index by two-thirds when compared with ligation only. The mean microvessel count per field in the infarcted myocardium of ILK-MSCs group was increased relative to the sham group and MSCs group. In conclusion, the ILK gene transduction of MSCs further assisted cell survival and adhesion, and improved myocardial damage when compared with MSC only after transplantation.

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Section: Discussionmentioning

confidence: 99%

Integrin-Linked Kinase Is Required in Hypoxic Mesenchymal Stem Cells for Strengthening Cell Adhesion to Ischemic Myocardium

et al. 2009

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“…Despite recent reports for their successful cardiomyogenic differentiation in vitro 3 , failure of skeletal myoblasts to electromechanically integrate and synchronously contract with the host myocytes post engraftment have restricted their use as the choice donor cells in clinical settings 4 . Similarly, cardiomyocytes are an excellent option for use as donor cells but their limited availability remains an issue of concern in clinical application 5,6 . Engraftment of non-myogenic fibroblasts and smooth muscle cells with contractility characteristics different from cardiomyocytes have also been shown to improve cardiac function 7,8 .…”

Section: An Overview Of Heart Cell Therapymentioning

confidence: 99%

Strategies to promote donor cell survival: Combining preconditioning approach with stem cell transplantation

Haider

Ashraf

2008

Journal of Molecular and Cellular Cardiology

185

152

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Stem cell transplantation has emerged as a potential modality in cardiovascular therapeutics due to their inherent characteristics of self-renewal, unlimited capacity for proliferation and ability to cross lineage restrictions and adopt different phenotypes. Constrained by extensive death in the unfriendly milieu of ischemic myocardium, the results of heart cell therapy in experimental animal models as well as clinical studies have been less than optimal. Several factors which play a role in early cell death after engraftment in the ischemic myocardium include; absence of survival factors in the transplanted heart, disruption of cell-cell interaction coupled with loss of survival signals from matrix attachments, insufficient vascular supply and elaboration of inflammatory cytokines resulting from ischemia and/or cell death. This article reviews various signaling pathways involved in triggering highly complex forms of cell death and provides critical appreciation of different novel anti-death strategies developed from the knowledge gained from using an ischemic preconditioning approach. The use of pharmacological preconditioning for up-regulation of pro-survival proteins and cardiogenic markers in the transplanted stem cells will be discussed. An overview of heart cell therapyDuring the last decade, widespread experimental studies in animal models and clinical studies have shown the safety, feasibility and efficacy of cell based therapies for myocardial regeneration. Starting with the use of unipotent myogenic cells including skeletal muscle derived stem cells and cardiomyocytes, heart cell therapy has progressed to assess the feasibility of multipotent and pluripotent stem cells for cardiac repair 1,2 . Despite recent reports for their successful cardiomyogenic differentiation in vitro 3 , failure of skeletal myoblasts to electromechanically integrate and synchronously contract with the host myocytes post engraftment have restricted their use as the choice donor cells in clinical settings 4 . Similarly, cardiomyocytes are an excellent option for use as donor cells but their limited availability remains an issue of concern in clinical application 5,6 . Engraftment of non-myogenic fibroblasts and smooth muscle cells with contractility characteristics different from cardiomyocytes have also been shown to improve cardiac function 7,8 . Nevertheless, a repertoire of stem and progenitor cells in the bone marrow with differing plasticity and differentiation potentials have emerged as the most extensively studied cells for their myocardial regenerative potential in experimental animals and clinical studies 9,10 . In case of bone marrow derived stem cell engraftment, the mainstay of mechanisms for cardiac repair is #Corresponding Author: Muhammad Ashraf, Ph.D, Department of Pathology and Laboratory Medicine, 231-Albert Sabin Way, University of Cincinnati, OH-45267-0529, USA. Fax:1-513-558-0807, E-mail:E-mail: muhammad.ashraf@uc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has bee...

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“…Fetal cardiomyocytes still can enter the cell cycle and be expanded in culture. Successful cell transplantation using fetal cardiomyocytes was initially demonstrated in mice (Soonpaa et al, 1994;Li et al, 1995;Li et al, 1996), with findings in improvement of heart function and formation of new blood vessels in and around the cell graft area (Watanabe et al, 1998). These experiments show that fetal cardiomyocyte transplantation is feasible and potentially clinically relevant.…”

Section: Stem Cell Basics and Selectionmentioning

confidence: 93%