Transplantation of Adipose Stromal Cell Sheet Producing Hepatocyte Growth Factor Induces Pleiotropic Effect in Ischemic Skeletal Muscle
Cell therapy remains a promising approach for the treatment of cardiovascular diseases. In this regard, the contemporary trend is the development of methods to overcome low cell viability and enhance their regenerative potential. In the present study, we evaluated the therapeutic potential of gene-m...
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| Veröffentlicht in: | International journal of molecular sciences 2019-06, Vol.20 (12), p.3088 |
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| creator | Boldyreva, Maria A Shevchenko, Evgeny K Molokotina, Yuliya D Makarevich, Pavel I Beloglazova, Irina B Zubkova, Ekaterina S Dergilev, Konstantin V Tsokolaeva, Zoya I Penkov, Dmitry Hsu, Mu-Nung Hu, Yu-Chen Parfyonova, Yelena V |
| description | Cell therapy remains a promising approach for the treatment of cardiovascular diseases. In this regard, the contemporary trend is the development of methods to overcome low cell viability and enhance their regenerative potential. In the present study, we evaluated the therapeutic potential of gene-modified adipose-derived stromal cells (ADSC) that overexpress hepatocyte growth factor (HGF) in a mice hind limb ischemia model. Angiogenic and neuroprotective effects were assessed following ADSC transplantation in suspension or in the form of cell sheet. We found superior blood flow restoration, tissue vascularization and innervation, and fibrosis reduction after transplantation of HGF-producing ADSC sheet compared to other groups. We suggest that the observed effects are determined by pleiotropic effects of HGF, along with the multifactorial paracrine action of ADSC which remain viable and functionally active within the engineered cell construct. Thus, we demonstrated the high therapeutic potential of the utilized approach for skeletal muscle recovery after ischemic damage associated with complex tissue degenerative effects. |
| doi_str_mv | 10.3390/ijms20123088 |
| format | Article |
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In this regard, the contemporary trend is the development of methods to overcome low cell viability and enhance their regenerative potential. In the present study, we evaluated the therapeutic potential of gene-modified adipose-derived stromal cells (ADSC) that overexpress hepatocyte growth factor (HGF) in a mice hind limb ischemia model. Angiogenic and neuroprotective effects were assessed following ADSC transplantation in suspension or in the form of cell sheet. We found superior blood flow restoration, tissue vascularization and innervation, and fibrosis reduction after transplantation of HGF-producing ADSC sheet compared to other groups. We suggest that the observed effects are determined by pleiotropic effects of HGF, along with the multifactorial paracrine action of ADSC which remain viable and functionally active within the engineered cell construct. Thus, we demonstrated the high therapeutic potential of the utilized approach for skeletal muscle recovery after ischemic damage associated with complex tissue degenerative effects.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20123088</identifier><identifier>PMID: 31238604</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adipose Tissue - cytology ; Angiogenesis ; Animals ; Cell adhesion & migration ; Cell Culture Techniques ; Cell Differentiation - genetics ; Cell Movement - drug effects ; Cell therapy ; Culture Media, Conditioned - pharmacology ; Damage prevention ; Disease Models, Animal ; Extracellular matrix ; Gene Expression ; Gene therapy ; Growth factors ; Hepatocyte growth factor ; Hepatocyte Growth Factor - biosynthesis ; Hepatocyte Growth Factor - genetics ; Humans ; Ischemia ; Mice ; Muscle Fibers, Skeletal - cytology ; Muscle Fibers, Skeletal - metabolism ; Muscle, Skeletal - blood supply ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - pathology ; Muscles ; Musculoskeletal system ; Neovascularization, Physiologic - drug effects ; Neovascularization, Physiologic - genetics ; Neuroglia - cytology ; Neuroglia - drug effects ; Neuroglia - metabolism ; Neuronal Outgrowth - drug effects ; Pericytes ; Risk analysis ; Risk factors ; Skeletal muscle ; Stromal Cells - metabolism ; Stromal Cells - transplantation ; Transplantation ; Vectors (Biology) ; Viability</subject><ispartof>International journal of molecular sciences, 2019-06, Vol.20 (12), p.3088</ispartof><rights>2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-ea1edb9fe810f6b24c72d54df1754a966a517d78836fde195eb2366940eded53</citedby><cites>FETCH-LOGICAL-c412t-ea1edb9fe810f6b24c72d54df1754a966a517d78836fde195eb2366940eded53</cites><orcidid>0000-0002-2345-3681 ; 0000-0001-8869-5190 ; 0000-0002-0512-3670</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627773/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627773/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31238604$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Boldyreva, Maria A</creatorcontrib><creatorcontrib>Shevchenko, Evgeny K</creatorcontrib><creatorcontrib>Molokotina, Yuliya D</creatorcontrib><creatorcontrib>Makarevich, Pavel I</creatorcontrib><creatorcontrib>Beloglazova, Irina B</creatorcontrib><creatorcontrib>Zubkova, Ekaterina S</creatorcontrib><creatorcontrib>Dergilev, Konstantin V</creatorcontrib><creatorcontrib>Tsokolaeva, Zoya I</creatorcontrib><creatorcontrib>Penkov, Dmitry</creatorcontrib><creatorcontrib>Hsu, Mu-Nung</creatorcontrib><creatorcontrib>Hu, Yu-Chen</creatorcontrib><creatorcontrib>Parfyonova, Yelena V</creatorcontrib><title>Transplantation of Adipose Stromal Cell Sheet Producing Hepatocyte Growth Factor Induces Pleiotropic Effect in Ischemic Skeletal Muscle</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Cell therapy remains a promising approach for the treatment of cardiovascular diseases. In this regard, the contemporary trend is the development of methods to overcome low cell viability and enhance their regenerative potential. In the present study, we evaluated the therapeutic potential of gene-modified adipose-derived stromal cells (ADSC) that overexpress hepatocyte growth factor (HGF) in a mice hind limb ischemia model. Angiogenic and neuroprotective effects were assessed following ADSC transplantation in suspension or in the form of cell sheet. We found superior blood flow restoration, tissue vascularization and innervation, and fibrosis reduction after transplantation of HGF-producing ADSC sheet compared to other groups. We suggest that the observed effects are determined by pleiotropic effects of HGF, along with the multifactorial paracrine action of ADSC which remain viable and functionally active within the engineered cell construct. Thus, we demonstrated the high therapeutic potential of the utilized approach for skeletal muscle recovery after ischemic damage associated with complex tissue degenerative effects.</description><subject>Adipose Tissue - cytology</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Cell adhesion & migration</subject><subject>Cell Culture Techniques</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Movement - drug effects</subject><subject>Cell therapy</subject><subject>Culture Media, Conditioned - pharmacology</subject><subject>Damage prevention</subject><subject>Disease Models, Animal</subject><subject>Extracellular matrix</subject><subject>Gene Expression</subject><subject>Gene therapy</subject><subject>Growth factors</subject><subject>Hepatocyte growth factor</subject><subject>Hepatocyte Growth Factor - biosynthesis</subject><subject>Hepatocyte Growth Factor - genetics</subject><subject>Humans</subject><subject>Ischemia</subject><subject>Mice</subject><subject>Muscle Fibers, Skeletal - 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In this regard, the contemporary trend is the development of methods to overcome low cell viability and enhance their regenerative potential. In the present study, we evaluated the therapeutic potential of gene-modified adipose-derived stromal cells (ADSC) that overexpress hepatocyte growth factor (HGF) in a mice hind limb ischemia model. Angiogenic and neuroprotective effects were assessed following ADSC transplantation in suspension or in the form of cell sheet. We found superior blood flow restoration, tissue vascularization and innervation, and fibrosis reduction after transplantation of HGF-producing ADSC sheet compared to other groups. We suggest that the observed effects are determined by pleiotropic effects of HGF, along with the multifactorial paracrine action of ADSC which remain viable and functionally active within the engineered cell construct. 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| ispartof | International journal of molecular sciences, 2019-06, Vol.20 (12), p.3088 |
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| language | eng |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; PubMed Central; EZB Electronic Journals Library |
| subjects | Adipose Tissue - cytology Angiogenesis Animals Cell adhesion & migration Cell Culture Techniques Cell Differentiation - genetics Cell Movement - drug effects Cell therapy Culture Media, Conditioned - pharmacology Damage prevention Disease Models, Animal Extracellular matrix Gene Expression Gene therapy Growth factors Hepatocyte growth factor Hepatocyte Growth Factor - biosynthesis Hepatocyte Growth Factor - genetics Humans Ischemia Mice Muscle Fibers, Skeletal - cytology Muscle Fibers, Skeletal - metabolism Muscle, Skeletal - blood supply Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Muscles Musculoskeletal system Neovascularization, Physiologic - drug effects Neovascularization, Physiologic - genetics Neuroglia - cytology Neuroglia - drug effects Neuroglia - metabolism Neuronal Outgrowth - drug effects Pericytes Risk analysis Risk factors Skeletal muscle Stromal Cells - metabolism Stromal Cells - transplantation Transplantation Vectors (Biology) Viability |
| title | Transplantation of Adipose Stromal Cell Sheet Producing Hepatocyte Growth Factor Induces Pleiotropic Effect in Ischemic Skeletal Muscle |
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