Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment
Human mesenchymal stem cells gather special interest as a universal and feasible add-on therapy for myocardial infarction (MI). In particular, human umbilical cord matrix-derived mesenchymal stromal cells (UCM-MSC) are advantageous since can be easily obtained and display high expansion potential. U...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.624601/full |
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| author | Tiago L. Laundos Tiago L. Laundos Tiago L. Laundos Francisco Vasques-Nóvoa Francisco Vasques-Nóvoa Francisco Vasques-Nóvoa Francisco Vasques-Nóvoa Rita N. Gomes Rita N. Gomes Rita N. Gomes Vasco Sampaio-Pinto Vasco Sampaio-Pinto Vasco Sampaio-Pinto Pedro Cruz Hélder Cruz Jorge M. Santos Rita N. Barcia Perpétua Pinto-do-Ó Perpétua Pinto-do-Ó Perpétua Pinto-do-Ó Diana S. Nascimento Diana S. Nascimento Diana S. Nascimento |
| author_facet | Tiago L. Laundos Tiago L. Laundos Tiago L. Laundos Francisco Vasques-Nóvoa Francisco Vasques-Nóvoa Francisco Vasques-Nóvoa Francisco Vasques-Nóvoa Rita N. Gomes Rita N. Gomes Rita N. Gomes Vasco Sampaio-Pinto Vasco Sampaio-Pinto Vasco Sampaio-Pinto Pedro Cruz Hélder Cruz Jorge M. Santos Rita N. Barcia Perpétua Pinto-do-Ó Perpétua Pinto-do-Ó Perpétua Pinto-do-Ó Diana S. Nascimento Diana S. Nascimento Diana S. Nascimento |
| author_sort | Tiago L. Laundos |
| collection | DOAJ |
| description | Human mesenchymal stem cells gather special interest as a universal and feasible add-on therapy for myocardial infarction (MI). In particular, human umbilical cord matrix-derived mesenchymal stromal cells (UCM-MSC) are advantageous since can be easily obtained and display high expansion potential. Using isolation protocols compliant with cell therapy, we previously showed UCM-MSC preserved cardiac function and attenuated remodeling 2 weeks after MI. In this study, UCM-MSC from two umbilical cords, UC-A and UC-B, were transplanted in a murine MI model to investigate consistency and durability of the therapeutic benefits. Both cellular products improved cardiac function and limited adverse cardiac remodeling 12 weeks post-ischemic injury, supporting sustained and long-term beneficial therapeutic effect. Donor associated variability was found in the modulation of cardiac remodeling and activation of the Akt-mTOR-GSK3β survival pathway. In vitro, the two cell products displayed similar ability to induce the formation of vessel-like structures and comparable transcriptome in normoxia and hypoxia, apart from UCM-MSCs proliferation and expression differences in a small subset of genes associated with MHC Class I. These findings support that UCM-MSC are strong candidates to assist the treatment of MI whilst calling for the discussion on methodologies to characterize and select best performing UCM-MSC before clinical application. |
| first_indexed | 2024-03-12T14:25:40Z |
| format | Article |
| id | doaj.art-d5f0948fe6014d4bbe26d57e13dde2e6 |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-12T14:25:40Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-d5f0948fe6014d4bbe26d57e13dde2e62023-08-18T08:17:24ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01910.3389/fcell.2021.624601624601Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient EngraftmentTiago L. Laundos0Tiago L. Laundos1Tiago L. Laundos2Francisco Vasques-Nóvoa3Francisco Vasques-Nóvoa4Francisco Vasques-Nóvoa5Francisco Vasques-Nóvoa6Rita N. Gomes7Rita N. Gomes8Rita N. Gomes9Vasco Sampaio-Pinto10Vasco Sampaio-Pinto11Vasco Sampaio-Pinto12Pedro Cruz13Hélder Cruz14Jorge M. Santos15Rita N. Barcia16Perpétua Pinto-do-Ó17Perpétua Pinto-do-Ó18Perpétua Pinto-do-Ó19Diana S. Nascimento20Diana S. Nascimento21Diana S. Nascimento22Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, PortugalInstituto Nacional de Engenharia Biomédica (INEB), University of Porto, Porto, PortugalInstituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, PortugalInstituto Nacional de Engenharia Biomédica (INEB), University of Porto, Porto, PortugalCardiovascular RandD Center, Faculty of Medicine of the University of Porto, Porto, PortugalDepartment of Internal Medicine, Centro Hospitalar Universitário São João, Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, PortugalInstituto Nacional de Engenharia Biomédica (INEB), University of Porto, Porto, PortugalInstituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, PortugalInstituto Nacional de Engenharia Biomédica (INEB), University of Porto, Porto, PortugalInstituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto, PortugalECBio S.A., Amadora, PortugalECBio S.A., Amadora, PortugalECBio S.A., Amadora, PortugalECBio S.A., Amadora, PortugalInstituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, PortugalInstituto Nacional de Engenharia Biomédica (INEB), University of Porto, Porto, PortugalInstituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, PortugalInstituto Nacional de Engenharia Biomédica (INEB), University of Porto, Porto, PortugalInstituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto, PortugalHuman mesenchymal stem cells gather special interest as a universal and feasible add-on therapy for myocardial infarction (MI). In particular, human umbilical cord matrix-derived mesenchymal stromal cells (UCM-MSC) are advantageous since can be easily obtained and display high expansion potential. Using isolation protocols compliant with cell therapy, we previously showed UCM-MSC preserved cardiac function and attenuated remodeling 2 weeks after MI. In this study, UCM-MSC from two umbilical cords, UC-A and UC-B, were transplanted in a murine MI model to investigate consistency and durability of the therapeutic benefits. Both cellular products improved cardiac function and limited adverse cardiac remodeling 12 weeks post-ischemic injury, supporting sustained and long-term beneficial therapeutic effect. Donor associated variability was found in the modulation of cardiac remodeling and activation of the Akt-mTOR-GSK3β survival pathway. In vitro, the two cell products displayed similar ability to induce the formation of vessel-like structures and comparable transcriptome in normoxia and hypoxia, apart from UCM-MSCs proliferation and expression differences in a small subset of genes associated with MHC Class I. These findings support that UCM-MSC are strong candidates to assist the treatment of MI whilst calling for the discussion on methodologies to characterize and select best performing UCM-MSC before clinical application.https://www.frontiersin.org/articles/10.3389/fcell.2021.624601/fullmesenchymal stromal (or stem) cellsWharton's jellymyocardial infarctionregeneration/repairumbilical cord matrix derived mesenchymal stromal cells (hUCM-MSCs)cell therapy |
| spellingShingle | Tiago L. Laundos Tiago L. Laundos Tiago L. Laundos Francisco Vasques-Nóvoa Francisco Vasques-Nóvoa Francisco Vasques-Nóvoa Francisco Vasques-Nóvoa Rita N. Gomes Rita N. Gomes Rita N. Gomes Vasco Sampaio-Pinto Vasco Sampaio-Pinto Vasco Sampaio-Pinto Pedro Cruz Hélder Cruz Jorge M. Santos Rita N. Barcia Perpétua Pinto-do-Ó Perpétua Pinto-do-Ó Perpétua Pinto-do-Ó Diana S. Nascimento Diana S. Nascimento Diana S. Nascimento Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment Frontiers in Cell and Developmental Biology mesenchymal stromal (or stem) cells Wharton's jelly myocardial infarction regeneration/repair umbilical cord matrix derived mesenchymal stromal cells (hUCM-MSCs) cell therapy |
| title | Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment |
| title_full | Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment |
| title_fullStr | Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment |
| title_full_unstemmed | Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment |
| title_short | Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment |
| title_sort | consistent long term therapeutic efficacy of human umbilical cord matrix derived mesenchymal stromal cells after myocardial infarction despite individual differences and transient engraftment |
| topic | mesenchymal stromal (or stem) cells Wharton's jelly myocardial infarction regeneration/repair umbilical cord matrix derived mesenchymal stromal cells (hUCM-MSCs) cell therapy |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.624601/full |
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