title: Myogenic potential of whole bone marrow mesenchymal stem cells in vitro and in vivo for usage in urinary incontinence.
abstract: 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.
authors.affiliation: Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Turin, Italy. monica.gunetti@unito.it
authors.forename: Monica
authors.initials: M
authors.lastname: Gunetti
authors.forename: Simone
authors.initials: S
authors.lastname: Tomasi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giammò
authors.forename: Marina
authors.initials: M
authors.lastname: Boido
authors.forename: Deborah
authors.initials: D
authors.lastname: Rustichelli
authors.forename: Katia
authors.initials: K
authors.lastname: Mareschi
authors.forename: Edoardo
authors.initials: E
authors.lastname: Errichiello
authors.forename: Maurizio
authors.initials: M
authors.lastname: Parola
authors.forename: Ivana
authors.initials: I
authors.lastname: Ferrero
authors.forename: Franca
authors.initials: F
authors.lastname: Fagioli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vercelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Carone
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy; D018920:Coculture Techniques; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology; D032446:Myoblasts; D051381:Rats; D014549:Urinary Incontinence / Q000628:therapy
chemical_list: D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C)