Impact of Hepatocyte Growth Factor on Skeletal Myoblast Transplantation Late after Myocardial Infarction
In clinical studies, skeletal myoblast (SKMB) transplantation late after myocardial infarction (MI) has minimal impact on left ventricular (LV) function. This may be related to our previous observation that the extent of SKMB engraftment is minimal in chronic MI when compared to acute MI, which corr...
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| Format: | Article |
| Language: | English |
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AboutScience Srl
2013-01-01
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| Series: | Drug Target Insights |
| Online Access: | https://doi.org/10.4137/DTI.S11802 |
| _version_ | 1818557635961552896 |
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| author | Stacy B. O'blenes Audrey W. Li Chris Bowen Drew DeBay Mohammed Althobaiti James Clarke |
| author_facet | Stacy B. O'blenes Audrey W. Li Chris Bowen Drew DeBay Mohammed Althobaiti James Clarke |
| author_sort | Stacy B. O'blenes |
| collection | DOAJ |
| description | In clinical studies, skeletal myoblast (SKMB) transplantation late after myocardial infarction (MI) has minimal impact on left ventricular (LV) function. This may be related to our previous observation that the extent of SKMB engraftment is minimal in chronic MI when compared to acute MI, which correlates with decreased hepatocyte growth factor (HGF) expression, an important regulator of SKMB function. Here, we investigated delivery of exogenous HGF as a strategy for augmenting SKMB engraftment late after MI. Rats underwent SKMB transplantation 4 weeks after coronary ligation. HGF or vehicle control was delivered intravenously during the subsequent 2 weeks. LV function was assessed by MRI before and 2 weeks after SKMB transplantation. We evaluated HGF delivery, SKMB engraftment, and expression of genes associated with post-MI remodeling. Serum HGF was 6.2 ± 2.4 ng/mL after 2 weeks of HGF infusion (n = 7), but undetectable in controls (n = 7). LV end-diastolic volume and ejection fraction did not improve with HGF treatment (321 ± 27 mm 3 , 42% ± 2% vs. 285 ± 33 mm 3 , 43% ± 2%, HGF vs. control). MIs were larger in HGF-treated animals (50 ± 7 vs. 30 ± 6 mm 3 , P = 0.046), but the volume of engrafted SKMBs or percentage of MIs occupied by SKMBs did not increase with HGF (1.7 ± 0.3 mm 3 , 4.7% ± 1.9% vs. 1.4 ± 0.4 mm 3 , 5.3% ± 1.6%, HGF vs. control). Expression of genes associated with post-infarction remodeling was not altered by HGF. Delivery of exogenous HGF failed to augment SKMB engraftment and functional recovery in chronic MI. Expression of genes associated with LV remodeling was not altered by HGF. Alternative strategies to enhance engraftment of SKMB must be explored to optimize the clinical efficacy of SKMB transplantation. |
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| institution | Directory Open Access Journal |
| issn | 1177-3928 |
| language | English |
| last_indexed | 2024-12-14T00:02:07Z |
| publishDate | 2013-01-01 |
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| series | Drug Target Insights |
| spelling | doaj.art-83e8769345904bc3ab4b78e394f933692022-12-21T23:26:15ZengAboutScience SrlDrug Target Insights1177-39282013-01-01710.4137/DTI.S11802Impact of Hepatocyte Growth Factor on Skeletal Myoblast Transplantation Late after Myocardial InfarctionStacy B. O'blenes0Audrey W. Li1Chris Bowen2Drew DeBay3Mohammed Althobaiti4James Clarke5Dalhousie University Department of Physiology and Biophysics.Dalhousie University Department of Physiology and Biophysics.NRC Biomedical MRI Research Lab, Halifax, Nova Scotia, Canada.NRC Biomedical MRI Research Lab, Halifax, Nova Scotia, Canada.Dalhousie University Department of Radiology, Nova Scotia, Canada.Dalhousie University Department of Radiology, Nova Scotia, Canada.In clinical studies, skeletal myoblast (SKMB) transplantation late after myocardial infarction (MI) has minimal impact on left ventricular (LV) function. This may be related to our previous observation that the extent of SKMB engraftment is minimal in chronic MI when compared to acute MI, which correlates with decreased hepatocyte growth factor (HGF) expression, an important regulator of SKMB function. Here, we investigated delivery of exogenous HGF as a strategy for augmenting SKMB engraftment late after MI. Rats underwent SKMB transplantation 4 weeks after coronary ligation. HGF or vehicle control was delivered intravenously during the subsequent 2 weeks. LV function was assessed by MRI before and 2 weeks after SKMB transplantation. We evaluated HGF delivery, SKMB engraftment, and expression of genes associated with post-MI remodeling. Serum HGF was 6.2 ± 2.4 ng/mL after 2 weeks of HGF infusion (n = 7), but undetectable in controls (n = 7). LV end-diastolic volume and ejection fraction did not improve with HGF treatment (321 ± 27 mm 3 , 42% ± 2% vs. 285 ± 33 mm 3 , 43% ± 2%, HGF vs. control). MIs were larger in HGF-treated animals (50 ± 7 vs. 30 ± 6 mm 3 , P = 0.046), but the volume of engrafted SKMBs or percentage of MIs occupied by SKMBs did not increase with HGF (1.7 ± 0.3 mm 3 , 4.7% ± 1.9% vs. 1.4 ± 0.4 mm 3 , 5.3% ± 1.6%, HGF vs. control). Expression of genes associated with post-infarction remodeling was not altered by HGF. Delivery of exogenous HGF failed to augment SKMB engraftment and functional recovery in chronic MI. Expression of genes associated with LV remodeling was not altered by HGF. Alternative strategies to enhance engraftment of SKMB must be explored to optimize the clinical efficacy of SKMB transplantation.https://doi.org/10.4137/DTI.S11802 |
| spellingShingle | Stacy B. O'blenes Audrey W. Li Chris Bowen Drew DeBay Mohammed Althobaiti James Clarke Impact of Hepatocyte Growth Factor on Skeletal Myoblast Transplantation Late after Myocardial Infarction Drug Target Insights |
| title | Impact of Hepatocyte Growth Factor on Skeletal Myoblast Transplantation Late after Myocardial Infarction |
| title_full | Impact of Hepatocyte Growth Factor on Skeletal Myoblast Transplantation Late after Myocardial Infarction |
| title_fullStr | Impact of Hepatocyte Growth Factor on Skeletal Myoblast Transplantation Late after Myocardial Infarction |
| title_full_unstemmed | Impact of Hepatocyte Growth Factor on Skeletal Myoblast Transplantation Late after Myocardial Infarction |
| title_short | Impact of Hepatocyte Growth Factor on Skeletal Myoblast Transplantation Late after Myocardial Infarction |
| title_sort | impact of hepatocyte growth factor on skeletal myoblast transplantation late after myocardial infarction |
| url | https://doi.org/10.4137/DTI.S11802 |
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