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TRANSPLANTATION OF IPS CELLS REDUCES APOPTOSIS AND FIBROSIS AND IMPROVES CARDIAC FUNCTION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS
- Date Issued:
- 2010
- Abstract/Description:
- Background: Streptozotocin (STZ) induced diabetes leads to various complications including cardiomyopathy. Recent data suggests transplanted bone marrow stem cells improve cardiac function in diabetic cardiomyopathy. However, whether modified ES, iPS cells, or factors released from these cells can inhibit apoptosis and fibrosis remains completely unknown. The present study was designed to determine the effects of transplanted ES cells overexpressing pancreatic transcription factor 1 a (Ptf1a), a pro-pancreatic endodermal transcription factor, iPS cells, or their respective conditioned media (CM) on diabetic cardiomyopathy. Methods: Experimental diabetes was induced in male Sprague Dawley rats (8-10 weeks old) by intraperitoneal STZ injections (65 mg/kg body weight for 2 consecutive days). Animals were divided into six experimental groups including control, treated with sodium citrate buffer IP, STZ, STZ + ES-Ptf1a cells, STZ + iPS cells, STZ + ES-Ptf1a CM and STZ + iPS CM. Following STZ injections, appropriate cells (1 X 106/mL/injection/day) or CM (2 mL injection/day) were given intravenously for 3 consecutive days. Animals were sacrificed and hearts were harvested at day 28. Histology, TUNEL staining, and Caspase-3 activity were used to assess apoptosis and fibrosis. ERK1/2 phosphorylation was quantified using ELISAs. M-mode echocardiography fractional shortening was used to assess cardiac function. Results: Animals transplanted with ES cells, iPS cells, or both CMs showed a significant (p<0.05) reduction in interstitial fibrosis, and apoptosis compared with STZ group. ERK expression was not significantly different compared with STZ. Echocardiography showed a significant (p<0.05) improvement in fractional shortening in cell and media transplanted groups compared with STZ. Conclusions: Our data suggest that ES cells, iPS cells, and/or CMs inhibit apoptosis, reduce fibrosis, and improve cardiac function in STZ-treated diabetic rats.
Title: | TRANSPLANTATION OF IPS CELLS REDUCES APOPTOSIS AND FIBROSIS AND IMPROVES CARDIAC FUNCTION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS. |
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Name(s): |
Neel, Sarah, Author Singla, Dinender, Committee Chair University of Central Florida, Degree Grantor |
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Type of Resource: | text | |
Date Issued: | 2010 | |
Publisher: | University of Central Florida | |
Language(s): | English | |
Abstract/Description: | Background: Streptozotocin (STZ) induced diabetes leads to various complications including cardiomyopathy. Recent data suggests transplanted bone marrow stem cells improve cardiac function in diabetic cardiomyopathy. However, whether modified ES, iPS cells, or factors released from these cells can inhibit apoptosis and fibrosis remains completely unknown. The present study was designed to determine the effects of transplanted ES cells overexpressing pancreatic transcription factor 1 a (Ptf1a), a pro-pancreatic endodermal transcription factor, iPS cells, or their respective conditioned media (CM) on diabetic cardiomyopathy. Methods: Experimental diabetes was induced in male Sprague Dawley rats (8-10 weeks old) by intraperitoneal STZ injections (65 mg/kg body weight for 2 consecutive days). Animals were divided into six experimental groups including control, treated with sodium citrate buffer IP, STZ, STZ + ES-Ptf1a cells, STZ + iPS cells, STZ + ES-Ptf1a CM and STZ + iPS CM. Following STZ injections, appropriate cells (1 X 106/mL/injection/day) or CM (2 mL injection/day) were given intravenously for 3 consecutive days. Animals were sacrificed and hearts were harvested at day 28. Histology, TUNEL staining, and Caspase-3 activity were used to assess apoptosis and fibrosis. ERK1/2 phosphorylation was quantified using ELISAs. M-mode echocardiography fractional shortening was used to assess cardiac function. Results: Animals transplanted with ES cells, iPS cells, or both CMs showed a significant (p<0.05) reduction in interstitial fibrosis, and apoptosis compared with STZ group. ERK expression was not significantly different compared with STZ. Echocardiography showed a significant (p<0.05) improvement in fractional shortening in cell and media transplanted groups compared with STZ. Conclusions: Our data suggest that ES cells, iPS cells, and/or CMs inhibit apoptosis, reduce fibrosis, and improve cardiac function in STZ-treated diabetic rats. | |
Identifier: | CFE0003512 (IID), ucf:48964 (fedora) | |
Note(s): |
2010-12-01 M.S. Medicine, Burnett College of Biomedical Sciences Masters This record was generated from author submitted information. |
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Subject(s): |
induced pluripotent stem cell cardiac function apoptosis fibrosis |
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Persistent Link to This Record: | http://purl.flvc.org/ucf/fd/CFE0003512 | |
Restrictions on Access: | public | |
Host Institution: | UCF |