Les cellules souches et la thérapie cellulaire génèrent un engouement certain aussi bien pour les... more Les cellules souches et la thérapie cellulaire génèrent un engouement certain aussi bien pour les biologistes que pour les cliniciens et le grand public. La recherche fondamentale en biologie du développement, en utilisant les cellules souches comme modèle d'étude permet d'aborder les régulations et mécanismes tant cellulaires que moléculaire impliquées au cours de l'embryogenèse, de l'histogenèse f?tale et de l'histogenèse adulte au cours du renouvellement tissulaire normal ou après une nécrose tissulaire. Le nombre de laboratoires s'intéressant à l'étude des cellules souches ne cesse de croître, il y a d'ores et déjà une répercutions sur l'enseignement supérieure et la formation au niveau des filières des sciences de le vie et de la santé. Ce présent manuel présentera les cellules souches et leurs applications actuelles et futures en thérapie chez l'Homme. L'ensemble des connaissances, définitions, concepts et théories autour de ces cellules, parfois fortement en contradiction sur la scène de la recherche sera également abordé et discuté.
We examined the expression and function of a gene we previously cloned from its downregulation in... more We examined the expression and function of a gene we previously cloned from its downregulation in a muscle atrophy model. The encoded protein was named myodulin because of sequence homologies with the cartilage-specific chondromodulin-I (ChM-I) protein, its restricted expression in skeletal muscle tissue, and its modulating properties on vascular endothelial cells described here. We investigated the expression of myodulin in muscle fibers and cultured muscle cells. Myodulin RNA messengers were found in muscle fibers and their tendon extensions. Overexpression of myodulin fused to a FLAG peptide showed evidence of a muscle cell surface protein. Myodulin functions were assessed from similarities with chondromodulin-I. Coculture experiments using C 2 C 12 mouse myoblasts or myotubes, which stably overexpress myodulin, with H5V mouse cardiac vascular endothelial cells revealed that myodulin had a very active role in the invasive action of endothelial cells, without any evidence of extracellular myodulin secretion. Our results suggest that myodulin may be a muscle angiogenic factor operating through direct cell-to-cell interactions. This role is consistent with the correlation between modulations in myodulin expression and modifications in muscle microvascularization associated with activity-dependent muscle mass variations. D
Cell-based therapies are used to treat bone defects. We recently described that human multipotent... more Cell-based therapies are used to treat bone defects. We recently described that human multipotent adipose-derived stem (hMADS) cells, which exhibit a normal karyotype, self renewal, and the maintenance of their differentiation properties, are able to differentiate into different lineages. Herein, we show that hMADS cells can differentiate into osteocyte-like cells. In the presence of a low amount of serum and EGF, hMADS cells express specific molecular markers, among which alkaline phosphatase, CBFA-1, osteocalcin, DMP1, PHEX, and podoplanin and develop functional gap-junctions. When loaded on a hardening injectable bone substitute (HIBS) biomaterial and injected subcutaneously into nude mice, hMADS cells develop mineralized woven bone 4 weeks after implantation. Thus hMADS cells represent a valuable tool for pharmacological and biological studies of osteoblast differentiation in vitro and bone development in vivo.
Mesenchymal stem cells have an intrinsic capacity to differentiate into various cell types in cul... more Mesenchymal stem cells have an intrinsic capacity to differentiate into various cell types in culture or after transplantation. Previously we have shown that multipotent stem cells derived from human adipose tissue (hMADS cells) were able to restore dystrophin expression after transplantation in mdx mice. In the current study, we investigated the mechanism of skeletal muscle phenotype acquisition by hMADS cells. We first tested various culture conditions to induce an intrinsic myogenic program in hMADS cells. Neither myotube formation nor Pax7, myf-5, MyoD and myogenin expression could be detected under these conditions. In contrast, when co-cultured with myoblasts, hMADS cells reproducibly contributed to hybrid myotube formation, expressed several muscle differentiation markers and had the ability to restore dystrophin expression in human dystrophic background. Interestingly, this myogenic conversion was not associated with the expression of key transcription factors for muscle determination/differentiation. Therefore, our results clearly demonstrated that acquisition of myogenic identity by hMADS cells did not occur via a bona fide determination/differentiation process. We propose a model of myogenic conversion of human mesenchymal stem cells derived from adipose tissue in which, only after fusion, transcription factors of myoblasts were able to program hMADS genome toward the skeletal muscle lineage.
We examined the expression and function of a gene we previously cloned from its downregulation in... more We examined the expression and function of a gene we previously cloned from its downregulation in a muscle atrophy model. The encoded protein was named myodulin because of sequence homologies with the cartilage-specific chondromodulin-I (ChM-I) protein, its restricted expression in skeletal muscle tissue, and its modulating properties on vascular endothelial cells described here. We investigated the expression of myodulin in muscle fibers and cultured muscle cells. Myodulin RNA messengers were found in muscle fibers and their tendon extensions. Overexpression of myodulin fused to a FLAG peptide showed evidence of a muscle cell surface protein. Myodulin functions were assessed from similarities with chondromodulin-I. Coculture experiments using C2C12 mouse myoblasts or myotubes, which stably overexpress myodulin, with H5V mouse cardiac vascular endothelial cells revealed that myodulin had a very active role in the invasive action of endothelial cells, without any evidence of extracellular myodulin secretion. Our results suggest that myodulin may be a muscle angiogenic factor operating through direct cell-to-cell interactions. This role is consistent with the correlation between modulations in myodulin expression and modifications in muscle microvascularization associated with activity-dependent muscle mass variations.
We previously showed that the phenotypes of adipocyte progenitors and macrophages were close. Usi... more We previously showed that the phenotypes of adipocyte progenitors and macrophages were close. Using functional analyses and microarray technology, we first tested whether this intriguing relationship was specific to adipocyte progenitors or could be shared with other progenitors. Measurements of phagocytic activity and gene profiling analysis of different progenitor cells revealed that the latter hypothesis should be retained. These results encouraged us to pursue and to confirm our analysis with a gold-standard stem cell population, embryonic stem cells or ESC. The transcriptomic profiles of ESC and macrophages were clustered together, unlike differentiated ESC. In addition, undifferentiated ESC displayed higher phagocytic activity than other progenitors, and they could phagocytoze apoptotic bodies. These data suggest that progenitors and stem cells share some characteristics of macrophages. This opens new perspectives on understanding stem cell phenotype and functionalities such as a putative role of stem cells in tissue remodeling by discarding dead cells but also their immunomodulation or fusion properties.
FR:
Notre laboratoire a isolé à partir de tissu adipeux provenant de nouveau-né, une population d... more FR: Notre laboratoire a isolé à partir de tissu adipeux provenant de nouveau-né, une population de cellules souches mésenchymateuses, dénommée cellules hMADS (human Multipotent Adipose-tissue Derived Stem cells). Les cellules hMADS présentent à l'échelle clonale les propriétés fondamentales associées aux cellules souches telles que la multipotentialité et l'auto-renouvellement. Après extravasion, in vitro ou consécutive à leur transplantation dans un organe secondaire, les cellules souches mésenchymateuses pourraient se différencier en des types cellulaires inhabituels. Nos résultats antérieurs montraient en effet que les cellules hMADS pouvaient, après transplantation dans le muscle Tibialis anterior de la souris mdx, contribuer à la formation de myofibres contenant des noyaux humains et exprimant la dystrophine humaine. L'objectif de ce travail a été d'élucider le mécanisme par lequel les cellules hMADS contribuent à la formation de myofibre squelettique. Dans ce but, nous avons essayé « d'engager » le programme myogénique en testant sur ces cellules de nombreuses conditions de culture. Seules les expériences de co-cultures avec des myoblastes ont permis de mettre en évidence la contribution des cellules hMADS à la formation de myotubes hybrides. Ces myotubes présentent un phénotype « normale » et expriment de nombreux gènes musculaires dont la dystrophine, codés par les noyaux issus de la fusion de cellules hMADS avec les myoblastes murins ou humains. Enfin, nous avons démontré que la conversion myogénique des cellules hMADS dans ces conditions n'était pas due à un processus de « détermination/différenciation », mais à une programmation subie des noyaux hMADS. Cette programmation se produirait après la fusion et nécessiterait l'action des facteurs de transcription myogénique (Myogenic Regulatory Factors) codés par les noyaux issus des myoblastes.
ENG: Our laboratory has isolated from human infant adipose tissue, a mesenchymal stem cell population, named hMADS cells (human Multipotent Adipose-Derived Stem cells). hMADS cells exhibit at the single-cell level fundamental stem cell properties such self-renewal and multipotentiality. In addition, mesenchymal stem cells may have an intrinsic capacity to differentiate into supplementary cell types in culture or after transplantation. Previously we have shown that hMADS cells were able to restore dystrophin expression after transplantation in mdx mice. In the current study, we investigated the mechanism of skeletal muscle phenotype acquisition by hMADS cells. We first tested various culture conditions to induce an intrinsic myogenic program in hMADS cells. Myotube formation and muscle determination/differentiation factors, i. e. Pax7, myf-5, MyoD and myogenin were assessed. No myogenic conversion could be detected under these conditions. In contrast, when co-cultured with myoblasts, hMADS cells reproducibly contributed to hybrid myotube formation, expressed several muscle differentiation markers and had the ability to restore dystrophin expression in human dystrophic background. Interestingly, this myogenic conversion was not associated by the expression of key transcription factors for muscle determination/differentiation. Therefore, our results clearly demonstrated that acquisition of myogenic identity by hMADS cells did not occur via a bona fide determination/differentiation process. We propose a model of myogenic conversion of human mesenchymal stem cells derived from adipose tissue in which, only after fusion, transcription factors of myoblasts were able to program hMADS genome toward the skeletal muscle lineage.
Les cellules souches et la thérapie cellulaire génèrent un engouement certain aussi bien pour les... more Les cellules souches et la thérapie cellulaire génèrent un engouement certain aussi bien pour les biologistes que pour les cliniciens et le grand public. La recherche fondamentale en biologie du développement, en utilisant les cellules souches comme modèle d'étude permet d'aborder les régulations et mécanismes tant cellulaires que moléculaire impliquées au cours de l'embryogenèse, de l'histogenèse f?tale et de l'histogenèse adulte au cours du renouvellement tissulaire normal ou après une nécrose tissulaire. Le nombre de laboratoires s'intéressant à l'étude des cellules souches ne cesse de croître, il y a d'ores et déjà une répercutions sur l'enseignement supérieure et la formation au niveau des filières des sciences de le vie et de la santé. Ce présent manuel présentera les cellules souches et leurs applications actuelles et futures en thérapie chez l'Homme. L'ensemble des connaissances, définitions, concepts et théories autour de ces cellules, parfois fortement en contradiction sur la scène de la recherche sera également abordé et discuté.
We examined the expression and function of a gene we previously cloned from its downregulation in... more We examined the expression and function of a gene we previously cloned from its downregulation in a muscle atrophy model. The encoded protein was named myodulin because of sequence homologies with the cartilage-specific chondromodulin-I (ChM-I) protein, its restricted expression in skeletal muscle tissue, and its modulating properties on vascular endothelial cells described here. We investigated the expression of myodulin in muscle fibers and cultured muscle cells. Myodulin RNA messengers were found in muscle fibers and their tendon extensions. Overexpression of myodulin fused to a FLAG peptide showed evidence of a muscle cell surface protein. Myodulin functions were assessed from similarities with chondromodulin-I. Coculture experiments using C 2 C 12 mouse myoblasts or myotubes, which stably overexpress myodulin, with H5V mouse cardiac vascular endothelial cells revealed that myodulin had a very active role in the invasive action of endothelial cells, without any evidence of extracellular myodulin secretion. Our results suggest that myodulin may be a muscle angiogenic factor operating through direct cell-to-cell interactions. This role is consistent with the correlation between modulations in myodulin expression and modifications in muscle microvascularization associated with activity-dependent muscle mass variations. D
Cell-based therapies are used to treat bone defects. We recently described that human multipotent... more Cell-based therapies are used to treat bone defects. We recently described that human multipotent adipose-derived stem (hMADS) cells, which exhibit a normal karyotype, self renewal, and the maintenance of their differentiation properties, are able to differentiate into different lineages. Herein, we show that hMADS cells can differentiate into osteocyte-like cells. In the presence of a low amount of serum and EGF, hMADS cells express specific molecular markers, among which alkaline phosphatase, CBFA-1, osteocalcin, DMP1, PHEX, and podoplanin and develop functional gap-junctions. When loaded on a hardening injectable bone substitute (HIBS) biomaterial and injected subcutaneously into nude mice, hMADS cells develop mineralized woven bone 4 weeks after implantation. Thus hMADS cells represent a valuable tool for pharmacological and biological studies of osteoblast differentiation in vitro and bone development in vivo.
Mesenchymal stem cells have an intrinsic capacity to differentiate into various cell types in cul... more Mesenchymal stem cells have an intrinsic capacity to differentiate into various cell types in culture or after transplantation. Previously we have shown that multipotent stem cells derived from human adipose tissue (hMADS cells) were able to restore dystrophin expression after transplantation in mdx mice. In the current study, we investigated the mechanism of skeletal muscle phenotype acquisition by hMADS cells. We first tested various culture conditions to induce an intrinsic myogenic program in hMADS cells. Neither myotube formation nor Pax7, myf-5, MyoD and myogenin expression could be detected under these conditions. In contrast, when co-cultured with myoblasts, hMADS cells reproducibly contributed to hybrid myotube formation, expressed several muscle differentiation markers and had the ability to restore dystrophin expression in human dystrophic background. Interestingly, this myogenic conversion was not associated with the expression of key transcription factors for muscle determination/differentiation. Therefore, our results clearly demonstrated that acquisition of myogenic identity by hMADS cells did not occur via a bona fide determination/differentiation process. We propose a model of myogenic conversion of human mesenchymal stem cells derived from adipose tissue in which, only after fusion, transcription factors of myoblasts were able to program hMADS genome toward the skeletal muscle lineage.
We examined the expression and function of a gene we previously cloned from its downregulation in... more We examined the expression and function of a gene we previously cloned from its downregulation in a muscle atrophy model. The encoded protein was named myodulin because of sequence homologies with the cartilage-specific chondromodulin-I (ChM-I) protein, its restricted expression in skeletal muscle tissue, and its modulating properties on vascular endothelial cells described here. We investigated the expression of myodulin in muscle fibers and cultured muscle cells. Myodulin RNA messengers were found in muscle fibers and their tendon extensions. Overexpression of myodulin fused to a FLAG peptide showed evidence of a muscle cell surface protein. Myodulin functions were assessed from similarities with chondromodulin-I. Coculture experiments using C2C12 mouse myoblasts or myotubes, which stably overexpress myodulin, with H5V mouse cardiac vascular endothelial cells revealed that myodulin had a very active role in the invasive action of endothelial cells, without any evidence of extracellular myodulin secretion. Our results suggest that myodulin may be a muscle angiogenic factor operating through direct cell-to-cell interactions. This role is consistent with the correlation between modulations in myodulin expression and modifications in muscle microvascularization associated with activity-dependent muscle mass variations.
We previously showed that the phenotypes of adipocyte progenitors and macrophages were close. Usi... more We previously showed that the phenotypes of adipocyte progenitors and macrophages were close. Using functional analyses and microarray technology, we first tested whether this intriguing relationship was specific to adipocyte progenitors or could be shared with other progenitors. Measurements of phagocytic activity and gene profiling analysis of different progenitor cells revealed that the latter hypothesis should be retained. These results encouraged us to pursue and to confirm our analysis with a gold-standard stem cell population, embryonic stem cells or ESC. The transcriptomic profiles of ESC and macrophages were clustered together, unlike differentiated ESC. In addition, undifferentiated ESC displayed higher phagocytic activity than other progenitors, and they could phagocytoze apoptotic bodies. These data suggest that progenitors and stem cells share some characteristics of macrophages. This opens new perspectives on understanding stem cell phenotype and functionalities such as a putative role of stem cells in tissue remodeling by discarding dead cells but also their immunomodulation or fusion properties.
FR:
Notre laboratoire a isolé à partir de tissu adipeux provenant de nouveau-né, une population d... more FR: Notre laboratoire a isolé à partir de tissu adipeux provenant de nouveau-né, une population de cellules souches mésenchymateuses, dénommée cellules hMADS (human Multipotent Adipose-tissue Derived Stem cells). Les cellules hMADS présentent à l'échelle clonale les propriétés fondamentales associées aux cellules souches telles que la multipotentialité et l'auto-renouvellement. Après extravasion, in vitro ou consécutive à leur transplantation dans un organe secondaire, les cellules souches mésenchymateuses pourraient se différencier en des types cellulaires inhabituels. Nos résultats antérieurs montraient en effet que les cellules hMADS pouvaient, après transplantation dans le muscle Tibialis anterior de la souris mdx, contribuer à la formation de myofibres contenant des noyaux humains et exprimant la dystrophine humaine. L'objectif de ce travail a été d'élucider le mécanisme par lequel les cellules hMADS contribuent à la formation de myofibre squelettique. Dans ce but, nous avons essayé « d'engager » le programme myogénique en testant sur ces cellules de nombreuses conditions de culture. Seules les expériences de co-cultures avec des myoblastes ont permis de mettre en évidence la contribution des cellules hMADS à la formation de myotubes hybrides. Ces myotubes présentent un phénotype « normale » et expriment de nombreux gènes musculaires dont la dystrophine, codés par les noyaux issus de la fusion de cellules hMADS avec les myoblastes murins ou humains. Enfin, nous avons démontré que la conversion myogénique des cellules hMADS dans ces conditions n'était pas due à un processus de « détermination/différenciation », mais à une programmation subie des noyaux hMADS. Cette programmation se produirait après la fusion et nécessiterait l'action des facteurs de transcription myogénique (Myogenic Regulatory Factors) codés par les noyaux issus des myoblastes.
ENG: Our laboratory has isolated from human infant adipose tissue, a mesenchymal stem cell population, named hMADS cells (human Multipotent Adipose-Derived Stem cells). hMADS cells exhibit at the single-cell level fundamental stem cell properties such self-renewal and multipotentiality. In addition, mesenchymal stem cells may have an intrinsic capacity to differentiate into supplementary cell types in culture or after transplantation. Previously we have shown that hMADS cells were able to restore dystrophin expression after transplantation in mdx mice. In the current study, we investigated the mechanism of skeletal muscle phenotype acquisition by hMADS cells. We first tested various culture conditions to induce an intrinsic myogenic program in hMADS cells. Myotube formation and muscle determination/differentiation factors, i. e. Pax7, myf-5, MyoD and myogenin were assessed. No myogenic conversion could be detected under these conditions. In contrast, when co-cultured with myoblasts, hMADS cells reproducibly contributed to hybrid myotube formation, expressed several muscle differentiation markers and had the ability to restore dystrophin expression in human dystrophic background. Interestingly, this myogenic conversion was not associated by the expression of key transcription factors for muscle determination/differentiation. Therefore, our results clearly demonstrated that acquisition of myogenic identity by hMADS cells did not occur via a bona fide determination/differentiation process. We propose a model of myogenic conversion of human mesenchymal stem cells derived from adipose tissue in which, only after fusion, transcription factors of myoblasts were able to program hMADS genome toward the skeletal muscle lineage.
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Notre laboratoire a isolé à partir de tissu adipeux provenant de nouveau-né, une population de cellules souches mésenchymateuses, dénommée cellules hMADS (human Multipotent Adipose-tissue Derived Stem cells). Les cellules hMADS présentent à l'échelle clonale les propriétés fondamentales associées aux cellules souches telles que la multipotentialité et l'auto-renouvellement.
Après extravasion, in vitro ou consécutive à leur transplantation dans un organe secondaire, les cellules souches mésenchymateuses pourraient se différencier en des types cellulaires inhabituels. Nos résultats antérieurs montraient en effet que les cellules hMADS pouvaient, après transplantation dans le muscle Tibialis anterior de la souris mdx, contribuer à la formation de myofibres contenant des noyaux humains et exprimant la dystrophine humaine.
L'objectif de ce travail a été d'élucider le mécanisme par lequel les cellules hMADS contribuent à la formation de myofibre squelettique. Dans ce but, nous avons essayé « d'engager » le programme myogénique en testant sur ces cellules de nombreuses conditions de culture. Seules les expériences de co-cultures avec des myoblastes ont permis de mettre en évidence la contribution des cellules hMADS à la formation de myotubes hybrides. Ces myotubes présentent un phénotype « normale » et expriment de nombreux gènes musculaires dont la dystrophine, codés par les noyaux issus de la fusion de cellules hMADS avec les myoblastes murins ou humains.
Enfin, nous avons démontré que la conversion myogénique des cellules hMADS dans ces conditions n'était pas due à un processus de « détermination/différenciation », mais à une programmation subie des noyaux hMADS. Cette programmation se produirait après la fusion et nécessiterait l'action des facteurs de transcription myogénique (Myogenic Regulatory Factors) codés par les noyaux issus des myoblastes.
ENG:
Our laboratory has isolated from human infant adipose tissue, a mesenchymal stem cell population, named hMADS cells (human Multipotent Adipose-Derived Stem cells). hMADS cells exhibit at the single-cell level fundamental stem cell properties such self-renewal and multipotentiality.
In addition, mesenchymal stem cells may have an intrinsic capacity to differentiate into supplementary cell types in culture or after transplantation. Previously we have shown that hMADS cells were able to restore dystrophin expression after transplantation in mdx mice. In the current study, we investigated the mechanism of skeletal muscle phenotype acquisition by hMADS cells. We first tested various culture conditions to induce an intrinsic myogenic program in hMADS cells. Myotube formation and muscle determination/differentiation factors, i. e. Pax7, myf-5, MyoD and myogenin were assessed. No myogenic conversion could be detected under these conditions. In contrast, when co-cultured with myoblasts, hMADS cells reproducibly contributed to hybrid myotube formation, expressed several muscle differentiation markers and had the ability to restore dystrophin expression in human dystrophic background. Interestingly, this myogenic conversion was not associated by the expression of key transcription factors for muscle determination/differentiation.
Therefore, our results clearly demonstrated that acquisition of myogenic identity by hMADS cells did not occur via a bona fide determination/differentiation process. We propose a model of myogenic conversion of human mesenchymal stem cells derived from adipose tissue in which, only after fusion, transcription factors of myoblasts were able to program hMADS genome toward the skeletal muscle lineage.
Notre laboratoire a isolé à partir de tissu adipeux provenant de nouveau-né, une population de cellules souches mésenchymateuses, dénommée cellules hMADS (human Multipotent Adipose-tissue Derived Stem cells). Les cellules hMADS présentent à l'échelle clonale les propriétés fondamentales associées aux cellules souches telles que la multipotentialité et l'auto-renouvellement.
Après extravasion, in vitro ou consécutive à leur transplantation dans un organe secondaire, les cellules souches mésenchymateuses pourraient se différencier en des types cellulaires inhabituels. Nos résultats antérieurs montraient en effet que les cellules hMADS pouvaient, après transplantation dans le muscle Tibialis anterior de la souris mdx, contribuer à la formation de myofibres contenant des noyaux humains et exprimant la dystrophine humaine.
L'objectif de ce travail a été d'élucider le mécanisme par lequel les cellules hMADS contribuent à la formation de myofibre squelettique. Dans ce but, nous avons essayé « d'engager » le programme myogénique en testant sur ces cellules de nombreuses conditions de culture. Seules les expériences de co-cultures avec des myoblastes ont permis de mettre en évidence la contribution des cellules hMADS à la formation de myotubes hybrides. Ces myotubes présentent un phénotype « normale » et expriment de nombreux gènes musculaires dont la dystrophine, codés par les noyaux issus de la fusion de cellules hMADS avec les myoblastes murins ou humains.
Enfin, nous avons démontré que la conversion myogénique des cellules hMADS dans ces conditions n'était pas due à un processus de « détermination/différenciation », mais à une programmation subie des noyaux hMADS. Cette programmation se produirait après la fusion et nécessiterait l'action des facteurs de transcription myogénique (Myogenic Regulatory Factors) codés par les noyaux issus des myoblastes.
ENG:
Our laboratory has isolated from human infant adipose tissue, a mesenchymal stem cell population, named hMADS cells (human Multipotent Adipose-Derived Stem cells). hMADS cells exhibit at the single-cell level fundamental stem cell properties such self-renewal and multipotentiality.
In addition, mesenchymal stem cells may have an intrinsic capacity to differentiate into supplementary cell types in culture or after transplantation. Previously we have shown that hMADS cells were able to restore dystrophin expression after transplantation in mdx mice. In the current study, we investigated the mechanism of skeletal muscle phenotype acquisition by hMADS cells. We first tested various culture conditions to induce an intrinsic myogenic program in hMADS cells. Myotube formation and muscle determination/differentiation factors, i. e. Pax7, myf-5, MyoD and myogenin were assessed. No myogenic conversion could be detected under these conditions. In contrast, when co-cultured with myoblasts, hMADS cells reproducibly contributed to hybrid myotube formation, expressed several muscle differentiation markers and had the ability to restore dystrophin expression in human dystrophic background. Interestingly, this myogenic conversion was not associated by the expression of key transcription factors for muscle determination/differentiation.
Therefore, our results clearly demonstrated that acquisition of myogenic identity by hMADS cells did not occur via a bona fide determination/differentiation process. We propose a model of myogenic conversion of human mesenchymal stem cells derived from adipose tissue in which, only after fusion, transcription factors of myoblasts were able to program hMADS genome toward the skeletal muscle lineage.