Increasing Transplanted Cell Survival With Cell-Based Angiogenic Gene Therapy

Yau, Terrence M.; Kim, Christopher; Ng, Dawn V Y; Li, Guangming; Zhang, Yaoguang; Weisel, Richard D.; Li, Ren‐Ke

doi:10.1016/j.athoracsur.2005.04.079

Cited by 64 publications

(44 citation statements)

References 26 publications

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“…An alternative strategy to the use of recombinant growth factors to precondition stem cells is to genetically modulate the cells for overexpression of the growth factor/s of interest [28,29,78,123]. The stem and progenitor cells are excellent carriers of therapeutic genes and can be manipulated for therapeutic gene overexpression without compromising their stemness characteristics.…”

Section: Transgenic Overexpression Of Growth Factors Preconditions Stmentioning

confidence: 99%

Preconditioning and Stem Cell Survival

Haider

Ashraf

2009

J. of Cardiovasc. Trans. Res.

111

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The harsh ischemic and cytokine-rich microenvironment in the infarcted myocardium, infiltrated by the inflammatory and immune cells, offers a significant challenge to the transplanted donor stem cells. Massive cell death occurs during transplantation as well as following engraftment which significantly lowers the effectiveness of the heart cell therapy. Various approaches have been adopted to overcome this problem nevertheless with multiple limitations with each of these current approaches. Cellular preconditioning and reprogramming by physical, chemical, genetic, and pharmacological manipulation of the cells has shown promise and "prime" the cells to the "state of readiness" to withstand the rigors of lethal ischemia in vitro as well as posttransplantation. This review summarizes the past and present novel approaches of ischemic preconditioning, pharmacological and genetic manipulation using preconditioning mimetics, recombinant growth factor protein treatment, and reprogramming of stem cells to overexpress survival signaling molecules, microRNAs, and trophic factors for intracrine, autocrine, and paracrine effects on cytoprotection.

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Section: Transgenic Overexpression Of Growth Factors Preconditions Stmentioning

confidence: 99%

Preconditioning and Stem Cell Survival

Haider

Ashraf

2009

J. of Cardiovasc. Trans. Res.

111

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“…[1][2][3][4] However, improvements in ventricular function were less impressive in the clinical trials than in animal studies, perhaps due to advanced age and comorbidities in the patients. Identifying the mechanisms responsible for the functional improvements may permit clinicians to adapt cell therapies for elderly patients.…”

mentioning

confidence: 99%

Skeletal Myoblasts Preserve Remote Matrix Architecture and Global Function When Implanted Early or Late After Coronary Ligation Into Infarcted or Remote Myocardium

et al. 2008

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Background-The inability of skeletal myoblasts to transdifferentiate into cardiomyocytes suggests that their beneficial effects on cardiac function after a myocardial infarction are mediated by paracrine effects. We evaluated the roles of these factors in the preservation of matrix architecture (in the infarct and remote regions) by varying the timing (postmyocardial infarction) and delivery site of the implanted cells. Methods and Results-Skeletal myoblasts (5ϫ10 6 ) or control media were injected into the infarct or noninfarcted myocardium at 5 or 30 days after coronary artery ligation in rats. Function was assessed by echocardiography before transplantation and 14 and 30 days thereafter and with a Millar catheter at 30 days after transplantation. Ventricular geometry, remote fibrillar collagen architecture, and changes in the matrix metalloproteinase-TIMP system were evaluated. Myoblast implantation in both sites and at both times preserved matrix architecture (length and width of collagen fibers) in the remote myocardium (in association with some decreases in remote myocardial matrix metalloprotease activity), improved global cardiac function, and attenuated the progressive increase in end diastolic volume (PϽ0.05 for all measures compared with medium controls). Cells delivered into the infarct region preserved scar thickness; cells delivered into the noninfarcted myocardium preserved wall thickness. Conclusions-Regardless of whether the cells were injected into the infarct or the noninfarcted myocardium early after an myocardial infarction or later, skeletal myoblasts improved cardiac function by preventing ventricular dilation and preserving matrix architecture in the remote region, likely mediated by paracrine effects. (Circulation. 2008;118[suppl 1]:S130-S137.)

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“…Indeed, the injection of a mixed population may provide some additional advantages. First, the formation of new vessels can aid in the survival of transplanted cells or endogenous ischemic cells [19,20]. Second, the presence of diverse differentiation stages may promote engraftment between CSC and the host myocardium.…”

Section: Mixed Cell Populationsmentioning

confidence: 99%

Adhesion Proteins, Stem Cells, and Arrhythmogenesis

Gillum

Sarvazyan

2008

Cardiovasc Toxicol

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Cell-transplantation therapy is a promising treatment option that is being actively explored as a way to repair cardiac muscle. The ultimate goal is to reconstitute the architecture of the cardiac muscle and to reestablish electrical propagation, while avoiding hypertrophy and scar formation. In this review, we focus on recent advances in the field as well as the difficulties encountered when the engraftment of cells into the host tissue is to be confirmed and functionally characterized. This is critical since incomplete or partial engraftment of transplanted cells within the host cardiac network exacerbates the heterogeneity already present in the injured myocardium and increases its propensity to arrhythmia. We conclude with a brief discussion of how the modulation of cell adhesion via modification of coupling proteins within transplanted cells may facilitate engraftment and alleviate the arrhythmogenic potential of cardiac grafts.

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Increasing Transplanted Cell Survival With Cell-Based Angiogenic Gene Therapy

Cited by 64 publications

References 26 publications

Preconditioning and Stem Cell Survival

Preconditioning and Stem Cell Survival

Skeletal Myoblasts Preserve Remote Matrix Architecture and Global Function When Implanted Early or Late After Coronary Ligation Into Infarcted or Remote Myocardium

Adhesion Proteins, Stem Cells, and Arrhythmogenesis

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