Intra‐arterial transplantation of
            <scp>HLA</scp>
            ‐matched donor mesoangioblasts in Duchenne muscular dystrophy

Cossu, Giulio; Previtali, Stefano C.; Napolitano, Sara; Cicalese, Maria Pia; Tedesco, Francesco Saverio; Nicastro, Francesca; Noviello, Maddalena; Roostalu, Urmas; Sora, Maria Grazia Natali; Scarlato, Marina; Pellegrin, Maurizio De; Godi, Claudia; Giuliani, Serena; Ciotti, Francesca; Tonlorenzi, Rossana; Lorenzetti, Isabella; Rivellini, Cristina; Benedetti, Sara; Gatti, Roberto; Marktel, Sarah; Mazzi, Benedetta; Tettamanti, Andrea; Ragazzi, Martina; Imro, Maria Adele; Marano, Giuseppina; Ambrosi, Alessandro; Fiori, Rossana; Sormani, Maria Pia; Bonini, Chiara; Venturini, Massimo; Politi, Letterio S.; Torrente, Yvan; Ciceri, Fabio

doi:10.15252/emmm.201505636

Cited by 147 publications

(117 citation statements)

References 47 publications

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“…Golden retriever muscular dystrophy (GRMD) dogs injected intra-arterially with mesoangioblasts isolated from healthy dogs showed expression of dystrophin in muscle tissue, and improved muscle morphology and functionality [19,22]. Unfortunately, injection of mesoangioblasts in DMD patients has demonstrated only minimal efficacy so far [23].…”

Section: Cell Therapymentioning

confidence: 99%

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

Chiappalupi

Salvadori

Luca

et al. 2017

JFMK

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Duchenne muscular dystrophy (DMD) is a lethal X-linked pathology due to lack of dystrophin and characterized by progressive muscle degeneration, impaired locomotion and premature death. The chronic presence of inflammatory cells, fibrosis and fat deposition are hallmarks of DMD muscle tissue. Many different therapeutic approaches to DMD have been tested, including cell-based and gene-based approaches, exon skipping, induction of expression of the dystrophin paralogue, utrophin, and, most recently the application of the CASPR/Cas9 genome editing system. However, corticosteroid treatment remains the gold standard therapy, even if corticosteroids have shown multiple undesirable side effects. Sertoli cells (SeC) have long been known for their ability to produce immunomodulatory and trophic factors, and have been used in a plethora of experimental models of disease. Recently, microencapsulated porcine SeC (MC-SeC) injected intraperitoneally in dystrophic mice produced morphological and functional benefits in muscles thanks to their release into the circulation of anti-inflammatory factors and heregulin β1, a known inducer of utrophin expression, thus opening a new avenue in the treatment of DMD. In order to stress the potentiality of the use of MC-SeC in the treatment of DMD, here, we examine the principal therapeutic approaches to DMD, and the properties of SeC (either nude or encapsulated into alginate-based microcapsules) and their preclinical and clinical use. Finally, we discuss the potential and future development of this latter approach.Keywords: Duchenne muscular dystrophy; therapeutic approaches; Sertoli cell; muscle inflammation; myopathies; encapsulation; biomaterials Duchenne Muscular Dystrophy (DMD)Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy. Muscular dystrophies are a group of inherited muscle diseases characterized by mutations in specific genes and resulting in muscle degeneration, impaired locomotion and premature death [1,2]. DMD is an X-linked recessive pathology caused by mutations in the dystrophin gene (DMD) usually resulting in the complete absence of this protein. Dystrophin is an essential component of the dystrophin-associated protein complex (DAPC) at the sarcolemma, a complex that ensures the structural and functional integrity of the myofibers during contraction representing a mechanical link between the intracellular cytoskeleton and the extracellular matrix. Absence of dystrophin or other components of the DAPC compromises the integrity of the DAPC itself leading to a susceptibility of myofibers to degeneration

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Section: Cell Therapymentioning

confidence: 99%

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

Chiappalupi

Salvadori

Luca

et al. 2017

JFMK

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“…Given the unmet clinical need for DMD patient therapy, stem cell treatment was translated for use in patients and the first randomized clinical trial was recently completed. 20 However, stem cell clinical trials in DMD are facing several limitations such as the costs for GMP stem cell production, their source (heterologous or autologous), the dosage needed to reach a clinical benefit, the variability in disease progression and severity of DMD patients, and last but not less important the number of trial admissible patients. The results described above demonstrate the feasibility of engineered muscle-derived CD133+ SCs autologous transplantation in dystrophic well-characterized older dogs.…”

Section: Discussionmentioning

confidence: 99%

Adaptive Immune Response Impairs the Efficacy of Autologous Transplantation of Engineered Stem Cells in Dystrophic Dogs

Sitzia

Farini

Jardim³

et al. 2016

Molecular Therapy

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Duchenne muscular dystrophy is the most common genetic muscular dystrophy. It is caused by mutations in the dystrophin gene, leading to absence of muscular dystrophin and to progressive degeneration of skeletal muscle. We have demonstrated that the exon skipping method safely and efficiently brings to the expression of a functional dystrophin in dystrophic CD133+ cells injected scid/mdx mice. Golden Retriever muscular dystrophic (GRMD) dogs represent the best preclinical model of Duchenne muscular dystrophy, mimicking the human pathology in genotypic and phenotypic aspects. Here, we assess the capacity of intra-arterial delivered autologous engineered canine CD133+ cells of restoring dystrophin expression in Golden Retriever muscular dystrophy. This is the first demonstration of five-year follow up study, showing initial clinical amelioration followed by stabilization in mild and severe affected Golden Retriever muscular dystrophy dogs. The occurrence of T-cell response in three Golden Retriever muscular dystrophy dogs, consistent with a memory response boosted by the exon skipped-dystrophin protein, suggests an adaptive immune response against dystrophin.

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“…The systemic delivery of cells may be preferred, but little headway has been made in investigating systemic delivery-based rsif.royalsocietypublishing.org J. R. Soc. [25,65,158,159]. Moreover, these patients' quality of life could be exceedingly improved by providing at least a single functional muscle that would allow them to retain an ability to communicate (e.g.…”

Section: Transplantation Of In Vitro Fabricated Muscle Tissuesmentioning

confidence: 99%

Hydrogel biomaterials and their therapeutic potential for muscle injuries and muscular dystrophies

Lev¹,

Seliktar²

2018

J. R. Soc. Interface.

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Muscular diseases such as muscular dystrophies and muscle injuries constitute a large group of ailments that manifest as muscle weakness, atrophy or fibrosis. Although cell therapy is a promising treatment option, the delivery and retention of cells in the muscle is difficult and prevents sustained regeneration needed for adequate functional improvements. Various types of biomaterials with different physical and chemical properties have been developed to improve the delivery of cells and/or growth factors for treating muscle injuries. Hydrogels are a family of materials with distinct advantages for use as cell delivery systems in muscle injuries and ailments, including their mild processing conditions, their similarities to natural tissue extracellular matrix, and their ability to be delivered with less invasive approaches. Moreover, hydrogels can be made to completely degrade in the body, leaving behind their biological payload in a process that can enhance the therapeutic process. For these reasons, hydrogels have shown great potential as cell delivery matrices. This paper reviews a few of the hydrogel systems currently being applied together with cell therapy and/or growth factor delivery to promote the therapeutic repair of muscle injuries and muscle wasting diseases such as muscular dystrophies.

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Intra‐arterial transplantation of HLA ‐matched donor mesoangioblasts in Duchenne muscular dystrophy

Cited by 147 publications

References 47 publications

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

Adaptive Immune Response Impairs the Efficacy of Autologous Transplantation of Engineered Stem Cells in Dystrophic Dogs

Hydrogel biomaterials and their therapeutic potential for muscle injuries and muscular dystrophies

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