Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Extracell Vesicles ; 10(3): e12045, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33456725

RESUMO

Extracellular vesicles (EVs) from cardiac stromal cells, developed as therapeutic candidates, improve dystrophic muscle function when administered parenterally, but oral delivery remains untested. We find that casein, the dominant protein in breast milk, enhances the uptake and bioactivity of ingested heart-derived EVs, altering gene expression in blood cells and enhancing muscle function in mdx mice with muscular dystrophy. Thus, EVs, administered orally, are absorbed and exert disease-modifying bioactivity in vivo. Formulating EVs with casein enhances uptake and markedly expands the range of potential therapeutic applications.


Assuntos
Caseínas/metabolismo , Vesículas Extracelulares/metabolismo , Distrofias Musculares/terapia , Animais , Ingestão de Alimentos , Feminino , Camundongos , Camundongos Endogâmicos mdx , Leite Humano/metabolismo , Doenças Musculares/terapia , Mioblastos Cardíacos/metabolismo , Células Estromais/metabolismo
3.
JCI Insight ; 4(7)2019 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-30944252

RESUMO

Dystrophin deficiency leads to progressive muscle degeneration in Duchenne muscular dystrophy (DMD) patients. No known cure exists, and standard care relies on the use of antiinflammatory steroids, which are associated with side effects that complicate long-term use. Here, we report that a single intravenous dose of clinical-stage cardiac stromal cells, called cardiosphere-derived cells (CDCs), improves the dystrophic phenotype in mdx mice. CDCs augment cardiac and skeletal muscle function, partially reverse established heart damage, and boost the regenerative capacity of skeletal muscle. We further demonstrate that CDCs work by secreting exosomes, which normalize gene expression at the transcriptome level, and alter cell signaling and biological processes in mdx hearts and skeletal muscle. The work reported here motivated the ongoing HOPE-2 clinical trial of systemic CDC delivery to DMD patients, and identifies exosomes as next-generation cell-free therapeutic candidates for DMD.


Assuntos
Células-Tronco Adultas/transplante , Distrofina/metabolismo , Exossomos/metabolismo , Distrofia Muscular de Duchenne/terapia , Miocárdio/citologia , Células-Tronco Adultas/metabolismo , Animais , Modelos Animais de Doenças , Distrofina/genética , Feminino , Regulação da Expressão Gênica , Humanos , Injeções Intravenosas , Camundongos , Camundongos Endogâmicos mdx , Distrofia Muscular de Duchenne/genética , Mutação
4.
Stem Cell Reports ; 10(3): 942-955, 2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29478899

RESUMO

Genetic deficiency of dystrophin leads to disability and premature death in Duchenne muscular dystrophy (DMD), affecting the heart as well as skeletal muscle. Here, we report that clinical-stage cardiac progenitor cells, known as cardiosphere-derived cells (CDCs), improve cardiac and skeletal myopathy in the mdx mouse model of DMD. Injection of CDCs into the hearts of mdx mice augments cardiac function, ambulatory capacity, and survival. Exosomes secreted by human CDCs reproduce the benefits of CDCs in mdx mice and in human induced pluripotent stem cell-derived Duchenne cardiomyocytes. Surprisingly, CDCs and their exosomes also transiently restored partial expression of full-length dystrophin in mdx mice. The findings further motivate the testing of CDCs in Duchenne patients, while identifying exosomes as next-generation therapeutic candidates.


Assuntos
Exossomos/fisiologia , Distrofia Muscular de Duchenne/terapia , Animais , Terapia Baseada em Transplante de Células e Tecidos/métodos , Modelos Animais de Doenças , Distrofina/metabolismo , Exossomos/metabolismo , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Distrofia Muscular Animal/metabolismo , Distrofia Muscular Animal/terapia , Distrofia Muscular de Duchenne/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...