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Myogenic Potential of Whole Bone Marrow Mesenchymal Stem Cells In Vitro and In Vivo for Usage in Urinary Incontinence
Urinary incontinence, defined as the complaint of any involuntary loss of urine, is a pathological condition, which affects 30% females and 15% males over 60, often following a progressive decrease of rhabdosphincter cells due to increasing age or secondary to damage to the pelvic floor musculature,...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448658/ https://www.ncbi.nlm.nih.gov/pubmed/23029081 http://dx.doi.org/10.1371/journal.pone.0045538 |
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author | Gunetti, Monica Tomasi, Simone Giammò, Alessandro Boido, Marina Rustichelli, Deborah Mareschi, Katia Errichiello, Edoardo Parola, Maurizio Ferrero, Ivana Fagioli, Franca Vercelli, Alessandro Carone, Roberto |
author_facet | Gunetti, Monica Tomasi, Simone Giammò, Alessandro Boido, Marina Rustichelli, Deborah Mareschi, Katia Errichiello, Edoardo Parola, Maurizio Ferrero, Ivana Fagioli, Franca Vercelli, Alessandro Carone, Roberto |
author_sort | Gunetti, Monica |
collection | PubMed |
description | Urinary incontinence, defined as the complaint of any involuntary loss of urine, is a pathological condition, which affects 30% females and 15% males over 60, often following a progressive decrease of rhabdosphincter cells due to increasing age or secondary to damage to the pelvic floor musculature, connective tissue and/or nerves. Recently, stem cell therapy has been proposed as a source for cell replacement and for trophic support to the sphincter. To develop new therapeutic strategies for urinary incontinence, we studied the interaction between mesenchymal stem cells (MSCs) and muscle cells in vitro; thereafter, aiming at a clinical usage, we analyzed the supporting role of MSCs for muscle cells in vitro and in in vivo xenotransplantation. MSCs can express markers of the myogenic cell lineages and give rise, under specific cell culture conditions, to myotube-like structures. Nevertheless, we failed to obtain mixed myotubes both in vitro and in vivo. For in vivo transplantation, we tested a new protocol to collect human MSCs from whole bone marrow, to get larger numbers of cells. MSCs, when transplanted into the pelvic muscles close to the external urethral sphincter, survived for a long time in absence of immunosuppression, and migrated into the muscle among fibers, and towards neuromuscular endplates. Moreover, they showed low levels of cycling cells, and did not infiltrate blood vessels. We never observed formation of cell masses suggestive of tumorigenesis. Those which remained close to the injection site showed an immature phenotype, whereas those in the muscle had more elongated morphologies. Therefore, MSCs are safe and can be easily transplanted without risk of side effects in the pelvic muscles. Further studies are needed to elucidate their integration into muscle fibers, and to promote their muscular transdifferentiation either before or after transplantation. |
format | Online Article Text |
id | pubmed-3448658 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34486582012-10-01 Myogenic Potential of Whole Bone Marrow Mesenchymal Stem Cells In Vitro and In Vivo for Usage in Urinary Incontinence Gunetti, Monica Tomasi, Simone Giammò, Alessandro Boido, Marina Rustichelli, Deborah Mareschi, Katia Errichiello, Edoardo Parola, Maurizio Ferrero, Ivana Fagioli, Franca Vercelli, Alessandro Carone, Roberto PLoS One Research Article Urinary incontinence, defined as the complaint of any involuntary loss of urine, is a pathological condition, which affects 30% females and 15% males over 60, often following a progressive decrease of rhabdosphincter cells due to increasing age or secondary to damage to the pelvic floor musculature, connective tissue and/or nerves. Recently, stem cell therapy has been proposed as a source for cell replacement and for trophic support to the sphincter. To develop new therapeutic strategies for urinary incontinence, we studied the interaction between mesenchymal stem cells (MSCs) and muscle cells in vitro; thereafter, aiming at a clinical usage, we analyzed the supporting role of MSCs for muscle cells in vitro and in in vivo xenotransplantation. MSCs can express markers of the myogenic cell lineages and give rise, under specific cell culture conditions, to myotube-like structures. Nevertheless, we failed to obtain mixed myotubes both in vitro and in vivo. For in vivo transplantation, we tested a new protocol to collect human MSCs from whole bone marrow, to get larger numbers of cells. MSCs, when transplanted into the pelvic muscles close to the external urethral sphincter, survived for a long time in absence of immunosuppression, and migrated into the muscle among fibers, and towards neuromuscular endplates. Moreover, they showed low levels of cycling cells, and did not infiltrate blood vessels. We never observed formation of cell masses suggestive of tumorigenesis. Those which remained close to the injection site showed an immature phenotype, whereas those in the muscle had more elongated morphologies. Therefore, MSCs are safe and can be easily transplanted without risk of side effects in the pelvic muscles. Further studies are needed to elucidate their integration into muscle fibers, and to promote their muscular transdifferentiation either before or after transplantation. Public Library of Science 2012-09-21 /pmc/articles/PMC3448658/ /pubmed/23029081 http://dx.doi.org/10.1371/journal.pone.0045538 Text en © 2012 Gunetti et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Gunetti, Monica Tomasi, Simone Giammò, Alessandro Boido, Marina Rustichelli, Deborah Mareschi, Katia Errichiello, Edoardo Parola, Maurizio Ferrero, Ivana Fagioli, Franca Vercelli, Alessandro Carone, Roberto Myogenic Potential of Whole Bone Marrow Mesenchymal Stem Cells In Vitro and In Vivo for Usage in Urinary Incontinence |
title | Myogenic Potential of Whole Bone Marrow Mesenchymal Stem Cells In Vitro and In Vivo for Usage in Urinary Incontinence |
title_full | Myogenic Potential of Whole Bone Marrow Mesenchymal Stem Cells In Vitro and In Vivo for Usage in Urinary Incontinence |
title_fullStr | Myogenic Potential of Whole Bone Marrow Mesenchymal Stem Cells In Vitro and In Vivo for Usage in Urinary Incontinence |
title_full_unstemmed | Myogenic Potential of Whole Bone Marrow Mesenchymal Stem Cells In Vitro and In Vivo for Usage in Urinary Incontinence |
title_short | Myogenic Potential of Whole Bone Marrow Mesenchymal Stem Cells In Vitro and In Vivo for Usage in Urinary Incontinence |
title_sort | myogenic potential of whole bone marrow mesenchymal stem cells in vitro and in vivo for usage in urinary incontinence |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448658/ https://www.ncbi.nlm.nih.gov/pubmed/23029081 http://dx.doi.org/10.1371/journal.pone.0045538 |
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