Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential.
A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4572703?pdf=render |
| _version_ | 1818265331006701568 |
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| author | Francesca Oltolina Andrea Zamperone Donato Colangelo Luca Gregoletto Simone Reano Stefano Pietronave Simone Merlin Maria Talmon Eugenio Novelli Marco Diena Carmine Nicoletti Antonio Musarò Nicoletta Filigheddu Antonia Follenzi Maria Prat |
| author_facet | Francesca Oltolina Andrea Zamperone Donato Colangelo Luca Gregoletto Simone Reano Stefano Pietronave Simone Merlin Maria Talmon Eugenio Novelli Marco Diena Carmine Nicoletti Antonio Musarò Nicoletta Filigheddu Antonia Follenzi Maria Prat |
| author_sort | Francesca Oltolina |
| collection | DOAJ |
| description | A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol. |
| first_indexed | 2024-12-12T19:49:06Z |
| format | Article |
| id | doaj.art-2224d588b376464e80bba0f141f76867 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T19:49:06Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2224d588b376464e80bba0f141f768672022-12-22T00:14:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013799910.1371/journal.pone.0137999Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential.Francesca OltolinaAndrea ZamperoneDonato ColangeloLuca GregolettoSimone ReanoStefano PietronaveSimone MerlinMaria TalmonEugenio NovelliMarco DienaCarmine NicolettiAntonio MusaròNicoletta FilighedduAntonia FollenziMaria PratA major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol.http://europepmc.org/articles/PMC4572703?pdf=render |
| spellingShingle | Francesca Oltolina Andrea Zamperone Donato Colangelo Luca Gregoletto Simone Reano Stefano Pietronave Simone Merlin Maria Talmon Eugenio Novelli Marco Diena Carmine Nicoletti Antonio Musarò Nicoletta Filigheddu Antonia Follenzi Maria Prat Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential. PLoS ONE |
| title | Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential. |
| title_full | Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential. |
| title_fullStr | Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential. |
| title_full_unstemmed | Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential. |
| title_short | Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential. |
| title_sort | human cardiac progenitor spheroids exhibit enhanced engraftment potential |
| url | http://europepmc.org/articles/PMC4572703?pdf=render |
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