In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted Rats
The scant ability of cardiomyocytes to proliferate makes heart regeneration one of the biggest challenges of science. Current therapies do not contemplate heart re-muscularization. In this scenario, stem cell-based approaches have been proposed to overcome this lack of regeneration. We hypothesize t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/11/5/374 |
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| author | Diogo Biagi Evelyn Thais Fantozzi Julliana Carvalho Campos-Oliveira Marcus Vinicius Naghetini Antonio Fernando Ribeiro Sirlene Rodrigues Isabella Ogusuku Rubia Vanderlinde Michelle Lopes Araújo Christie Debora Bastos Mello Antonio Carlos Campos de Carvalho Marcos Valadares Estela Cruvinel Rafael Dariolli |
| author_facet | Diogo Biagi Evelyn Thais Fantozzi Julliana Carvalho Campos-Oliveira Marcus Vinicius Naghetini Antonio Fernando Ribeiro Sirlene Rodrigues Isabella Ogusuku Rubia Vanderlinde Michelle Lopes Araújo Christie Debora Bastos Mello Antonio Carlos Campos de Carvalho Marcos Valadares Estela Cruvinel Rafael Dariolli |
| author_sort | Diogo Biagi |
| collection | DOAJ |
| description | The scant ability of cardiomyocytes to proliferate makes heart regeneration one of the biggest challenges of science. Current therapies do not contemplate heart re-muscularization. In this scenario, stem cell-based approaches have been proposed to overcome this lack of regeneration. We hypothesize that early-stage hiPSC-derived cardiomyocytes (hiPSC-CMs) could enhance the cardiac function of rats after myocardial infarction (MI). Animals were subjected to the permanent occlusion of the left ventricle (LV) anterior descending coronary artery (LAD). Seven days after MI, early-stage hiPSC-CMs were injected intramyocardially. Rats were subjected to echocardiography pre-and post-treatment. Thirty days after the injections were administered, treated rats displayed 6.2% human cardiac grafts, which were characterized molecularly. Left ventricle ejection fraction (LVEF) was improved by 7.8% in cell-injected rats, while placebo controls showed an 18.2% deterioration. Additionally, cell-treated rats displayed a 92% and 56% increase in radial and circumferential strains, respectively. Human cardiac grafts maturate in situ, preserving proliferation with 10% Ki67 and 3% PHH3 positive nuclei. Grafts were perfused by host vasculature with no evidence for immune rejection nor ectopic tissue formations. Our findings support the use of early-stage hiPSC-CMs as an alternative therapy to treat MI. The next steps of preclinical development include efficacy studies in large animals on the path to clinical-grade regenerative therapy targeting human patients. |
| first_indexed | 2024-03-10T11:43:38Z |
| format | Article |
| id | doaj.art-ae1c7d746c0e48628b3ceee53cff2631 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T11:43:38Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-ae1c7d746c0e48628b3ceee53cff26312023-11-21T18:19:39ZengMDPI AGJournal of Personalized Medicine2075-44262021-05-0111537410.3390/jpm11050374In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted RatsDiogo Biagi0Evelyn Thais Fantozzi1Julliana Carvalho Campos-Oliveira2Marcus Vinicius Naghetini3Antonio Fernando Ribeiro4Sirlene Rodrigues5Isabella Ogusuku6Rubia Vanderlinde7Michelle Lopes Araújo Christie8Debora Bastos Mello9Antonio Carlos Campos de Carvalho10Marcos Valadares11Estela Cruvinel12Rafael Dariolli13PluriCell Biotech, São Paulo 05508-000, BrazilPluriCell Biotech, São Paulo 05508-000, BrazilPluriCell Biotech, São Paulo 05508-000, BrazilPluriCell Biotech, São Paulo 05508-000, BrazilPluriCell Biotech, São Paulo 05508-000, BrazilPluriCell Biotech, São Paulo 05508-000, BrazilPluriCell Biotech, São Paulo 05508-000, BrazilPluriCell Biotech, São Paulo 05508-000, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, BrazilPluriCell Biotech, São Paulo 05508-000, BrazilPluriCell Biotech, São Paulo 05508-000, BrazilPluriCell Biotech, São Paulo 05508-000, BrazilThe scant ability of cardiomyocytes to proliferate makes heart regeneration one of the biggest challenges of science. Current therapies do not contemplate heart re-muscularization. In this scenario, stem cell-based approaches have been proposed to overcome this lack of regeneration. We hypothesize that early-stage hiPSC-derived cardiomyocytes (hiPSC-CMs) could enhance the cardiac function of rats after myocardial infarction (MI). Animals were subjected to the permanent occlusion of the left ventricle (LV) anterior descending coronary artery (LAD). Seven days after MI, early-stage hiPSC-CMs were injected intramyocardially. Rats were subjected to echocardiography pre-and post-treatment. Thirty days after the injections were administered, treated rats displayed 6.2% human cardiac grafts, which were characterized molecularly. Left ventricle ejection fraction (LVEF) was improved by 7.8% in cell-injected rats, while placebo controls showed an 18.2% deterioration. Additionally, cell-treated rats displayed a 92% and 56% increase in radial and circumferential strains, respectively. Human cardiac grafts maturate in situ, preserving proliferation with 10% Ki67 and 3% PHH3 positive nuclei. Grafts were perfused by host vasculature with no evidence for immune rejection nor ectopic tissue formations. Our findings support the use of early-stage hiPSC-CMs as an alternative therapy to treat MI. The next steps of preclinical development include efficacy studies in large animals on the path to clinical-grade regenerative therapy targeting human patients.https://www.mdpi.com/2075-4426/11/5/374stem cell-therapyhuman induced pluripotent stem cellscardiomyocytesmyocardial infarctionheart failureregeneration |
| spellingShingle | Diogo Biagi Evelyn Thais Fantozzi Julliana Carvalho Campos-Oliveira Marcus Vinicius Naghetini Antonio Fernando Ribeiro Sirlene Rodrigues Isabella Ogusuku Rubia Vanderlinde Michelle Lopes Araújo Christie Debora Bastos Mello Antonio Carlos Campos de Carvalho Marcos Valadares Estela Cruvinel Rafael Dariolli In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted Rats Journal of Personalized Medicine stem cell-therapy human induced pluripotent stem cells cardiomyocytes myocardial infarction heart failure regeneration |
| title | In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted Rats |
| title_full | In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted Rats |
| title_fullStr | In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted Rats |
| title_full_unstemmed | In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted Rats |
| title_short | In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted Rats |
| title_sort | in situ maturated early stage human induced pluripotent stem cell derived cardiomyocytes improve cardiac function by enhancing segmental contraction in infarcted rats |
| topic | stem cell-therapy human induced pluripotent stem cells cardiomyocytes myocardial infarction heart failure regeneration |
| url | https://www.mdpi.com/2075-4426/11/5/374 |
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