Engraftment Is Optimal When Myoblasts Are Transplanted Early: The Role of Hepatocyte Growth Factor

O’Blenes, Stacy B.; Li, Audrey W.; Chen, Robert; Arora, Rakesh C.; Horackova, Magda

doi:10.1016/j.athoracsur.2009.12.007

Cited by 9 publications

(25 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar observations are mentioned in other reports [17,52]. A recent study compared transplantation of skeletal myoblasts in rats immediately and 5 weeks after coronary artery litigation, reporting increased engraftment in the early group and decreased scar thickness as well as increased scar area in the late group [39]. Unfortunately, no functional measures are presented.…”

Section: Preclinical Studiessupporting

confidence: 48%

See 1 more Smart Citation

Stem Cell Therapy for Myocardial Infarction: Are We Missing Time?

Horst

2010

Cardiology

View full text Add to dashboard Cite

The success of stem cell therapy in myocardial infarction (MI) is modest, and for stem cell therapy to be clinically effective fine-tuning in regard to timing, dosing, and the route of administration is required. Experimental studies suggest the existence of a temporal window of opportunity bound by the acute inflammatory response on one hand and by scar formation on the other. In the meantime, microenvironmental factors must favor stem cell homing, survival, differentiation, and integration for stem cell therapy to be effective. Clinical data on the optimal timing of treatment are scarce. Experimental studies and clinical subgroup analyses can provide a clue and useful guidance for further research. In this review, the fundamental mechanisms as well as trial results important for the determination of the optimal timing of stem cell therapy following MI are summarized and discussed. We conclude that optimization of stem cell therapy requires further research on the fundamental mechanisms responsible for stem cell homing, survival, differentiation, and integration. Clinically, randomized trials with bone-marrow-derived stem cells should be conducted timing therapy at different points within the first month after MI, which seems to be the most promising period for this cell type.

show abstract

Section: Preclinical Studiessupporting

confidence: 48%

“…However, several stem cell homing factors have been identified [29,33,34,35,36,37,38,39]. Table 1 lists some of the most important homing factors and the associated time course following MI.…”

Section: Stem Cell Therapymentioning

confidence: 99%

Stem Cell Therapy for Myocardial Infarction: Are We Missing Time?

Horst

2010

Cardiology

View full text Add to dashboard Cite

show abstract

“…Studies in primary rat skeletal myoblasts and the C2C12 murine cell line have also demonstrated a promotion of proliferation in response to HGF at concentrations ranging from 3 ng/ml to 50 ng/ml (Allen et al, 1995;Anastasi et al, 1997;O'Blenes et al, 2010). In contrast however, a separate study utilising rat satellite cells demonstrated a suppression of proliferation in response to HGF at concentrations greater than 10 ng/ml (Yamada et al, 2010).…”

Section: Introductionmentioning

confidence: 87%

“…This is followed by migration to the site of injury and subsequent differentiation (Grounds et al, 2002). The activation of satellite cells, subsequent expansion, and terminal differentiation of the myoblast population is regulated by growth factors, such as fibroblast growth factor (FGF), insulin growth factor-1 (IGF-1), transforming growth factor beta (TGF-beta), and hepatocyte growth factor (HGF) (Gal-Levi et al, 1998;Miller et al, 2000;O'Blenes et al, 2010;O'Reilly et al, 2008;Pownall & Isaacs, 2010;Yamada et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Dose-dependent modulation of myogenesis by HGF: implications for c-Met expression and downstream signalling pathways

et al. 2015

View full text Add to dashboard Cite

Hepatocyte growth factor (HGF) regulates satellite cell activation, proliferation, and differentiation. We analyzed the dose-dependent effects of HGF on myogenesis. Murine C2C12 and human donor-derived skeletal muscle myoblasts were treated with 0, 2, or 10 ng/ml HGF followed by assessment of proliferation and differentiation. HGF (2 ng/ml) significantly promoted cell division, but reduced myogenic commitment and fusion. Conversely, 10 ng/ml HGF reduced proliferative capability, but increased differentiation. c-Met expression analysis revealed significantly decreased expression in differentiating cells cultured with 2 ng/ml HGF, but increased expression in proliferating cells with 10 ng/ml HGF. Mitogen-activated protein kinase (MAPKs: ERK, JNK, or p38K) and phosphatidylinositol-3-kinase (PI3K) inhibition abrogated the HGF-stimulated increase in cell number. Interestingly, PI3K and p38 kinase facilitated the negative effect of HGF on proliferation, while ERK inhibition abrogated the HGF-mediated decrease in differentiation. Dose-dependent effects of HGF are mediated by changes in c-Met expression and downstream MAPK and PI3K signalling.

show abstract

“…13 To achieve long-term benefits of cell transplantation, the graft must resist apoptosis and restore blood flow at the host environment chronically deprived of nutrients and oxygen. Although a three-dimensional sheet structure provides the cells with intercellular and ECM contacts that in contrast to single cell injections initially protect the cells, 14 the sheets greatly suffer from the inactivity of the underlying morbid myocardium of chronic HF.…”

mentioning

confidence: 99%

Bcl-2 Improves Myoblast Sheet Therapy in Rat Chronic Heart Failure

Siltanen

Kitabayashi

Pätilä

et al. 2011

Tissue Engineering Part A

View full text Add to dashboard Cite

Myoblast transplantation therapy for chronic heart failure (HF) is impaired by early donor cell death and reduced graft viability. Although epicardial implantation of cell sheets can prevent the initial loss of transplanted cells, limited vascularization subjects the sheets to apoptotic stress. We studied the efficacy of antiapoptotic bcl2 in myoblast sheet therapy for rat chronic HF. Myocardial infarction was induced by left anterior descending coronary artery ligation and HF was allowed to develop for 4 weeks. Thereafter, wild type (L6-WT; n=16) or Bcl-2-expressing (L6-Bcl2; n=19) myoblast sheets were transplanted epicardially. Control rats (n=21) underwent left anterior descending coronary artery ligation and re-thoracotomy. Five rats were sham-operated in both surgeries. Four weeks after transplantation, only the L6-Bcl2 rats showed improved left ventricular ejection fraction. Their vascular density in the damaged myocardium was greater, and they had more proliferating cells. The L6-Bcl2 group had an increased amount of myocytes in the infarct area. Soluble factors from L6-Bcl2 sheets induced a 2.9-fold increase in endothelial cell proliferation, and enhanced endothelial wound healing as compared to the L6-WT sheets. These effects were inhibited by SU5416 and were thus dependent on Flt1/Flk1 signaling. In conclusion, bcl2 improves efficacy of myoblast sheet transplantation and promotes proangiogenic paracrine signaling.

show abstract

Engraftment Is Optimal When Myoblasts Are Transplanted Early: The Role of Hepatocyte Growth Factor

Cited by 9 publications

References 31 publications

Stem Cell Therapy for Myocardial Infarction: Are We Missing Time?

Stem Cell Therapy for Myocardial Infarction: Are We Missing Time?

Dose-dependent modulation of myogenesis by HGF: implications for c-Met expression and downstream signalling pathways

Bcl-2 Improves Myoblast Sheet Therapy in Rat Chronic Heart Failure

Contact Info

Product

Resources

About