Uso de células tronco para tratamento da cardiomiopatia da distrofia muscular de Duchenne
USA – a empresa Capricor está desenvolvendo um protocolo para tratamento da cardiomiopatia da distrofia muscular de Duchenne com células tronco. A empresa tem experiência no tratamento de outras doenças cardíacas. No Congresso da Associação Americana de Cardiologia eles apresentaram o estudo feito em camundongos com distrofia muscular. Os animais tratados com estas células tronco apresentaram melhora da função cardíaca, redução da fibrose, e recuperação da integridade das mitocôndrias. A cardiomiopatia é a maior causa de mortalidade na doença e este tratamento se mostra viável para controle desta manifestação.
O resumo em inglês pode ser lido abaixo:
(American Heart Association Meeting, 2014) Heart-derived Cell Therapy for Duchenne Cardiomyopathy: Cardiosphere-derived Cells and their Exosomes Improve Function, Restore Mitochondrial Integrity and Reverse Degenerative Changes in the Hearts of Mdx Mice
Mark A Aminzadeh, Rachel Tobin, Rachel Smith, Linda Marbán, Eduardo Marbán, Cedars-Sinai Heart Inst, Los Angeles, CA
Abstract
Introduction: Cardiosphere-derived cells (CDCs) promote cardiomyogenesis and angiogenesis, while inhibiting oxidative stress, inflammation and fibrosis, in both ischemic and nonischemic cardiomyopathy. The mdx mouse model of Duchenne muscular dystrophy develops cardiomyopathy due to dystrophin deficiency and the resultant intense oxidative stress, inflammation and apoptosis. Here we tested the hypothesis that transplantation of CDCs or of exosomes derived from CDCs (CDC-XO) may be beneficial in mdx mice.
Methods and Results: A total of 78 mice were studied at a point when global cardiac dysfunction was already evident by echocardiography. Wild-type syngeneic mouse CDCs (105 cells total), CDC-XO (70µg), or vehicle only were injected intramyocardially in 5 left ventricular (LV) sites in 10-month old mdx mice. LV ejection fraction markedly improved over 3 months after treatment either with CDC or CDC-XO compared to vehicle-treated mice (60.4±1.6 vs 48.1±2.2; p<0.005). The functional improvement was associated with enhanced Nrf2 activation, upregulation of Nrf2 downstream gene products, increased expression of mitochondrial transcription factor A and cellular mitochondrial content, restored expression of mitochondrial respiratory chain subunits, reduced collagen I and III deposition, and attenuated infiltration of inflammatory cells [CD68+ macrophages and CD3+ T cells] in the CDC or CDC-XO-treated mouse hearts. Mitochondrial swelling and disorganization of cristae, prominent in vehicle-treated hearts by electron microscopy, were reversed by CDC treatment. Concomitantly, CDC-treated mdx mice exhibited higher maximal exercise capacity compared to vehicle-treated mice over 3 months of follow up (p<0.05). Conclusions: Cardiac function and exercise capacity improved in mdx mice treated with either CDCs or CDC-XO, accompanied by enhanced activation of the antioxidative Nrf2 pathway, attenuation of inflammation, reduction in collagen content and fibrosis, and augmented cardiomyogenesis in CDC-treated mdx hearts. The findings raise the possibility that CDCs and/or CDC-derived exosomes may be useful therapeutically in patients with Duchenne cardiomyopathy.
Fonte: http://distrofiamuscular.net/principal.htm
