Stem cells against myodystrophy
Muscular dystrophy in mice was cured with the help of human stem cells
Nanonewsnet based on the materials of the University of Minnesota:
U of M researchers develop new muscular dystrophy treatment approach using human stem cellsScientists from the Lillehei Heart Institute of the University of Minnesota (University of Minnesota, U of M), USA, have achieved outstanding success in the treatment of muscular dystrophy in mice using human muscle progenitor cells derived from induced pluripotent stem cells.
A study published in the journal Cell Stem Cell (Human ES- and iPS-Derived Myogenic Progenitors Restore DYSTROPHIN and Improve Contractility upon Transplantation in Dystrophic Mice) describes a strategy for obtaining a rapidly dividing population of human skeletal myogenic progenitor cells (muscle-forming cells) derived from induced pluripotent stem (iPS) cells. iPS cells have all the potential of embryonic stem (ES) cells, but are obtained by reprogramming skin cells (fibroblasts). They may be specific to the patient, which reduces the likelihood of their immune rejection, and do not increase the intensity of passions around ethical issues related to the need to kill human embryos.
This is the first demonstration of the effectiveness of the treatment of muscular dystrophy with human stem cells. According to scientists (by the way, they were the first to use mouse embryonic cells for the treatment of muscular dystrophy), there is a significant lag in translating the results of studies using mouse stem cells into therapeutically significant work based on human stem cells. This lag significantly limits the development of cell therapy methods and delays their clinical trials.
The latest study by American scientists proves the validity of the concept of treating muscular dystrophy with human iPS cells, preparing the ground for future clinical methods.
"One of the biggest obstacles to the development of cell therapy for neuromuscular disorders, such as muscular dystrophy, was obtaining sufficient amounts of muscle progenitor cells to achieve a therapeutically effective response," explains the study leader, Associate Professor of Medicine Rita Perlingeiro, PhD. "Our results show that obtaining skeletal muscle stem cells suitable for transplantation from human pluripotent stem cells is indeed possible and creates the basis for the development of a clinically significant therapeutic approach."
Human skeletal muscle progenitor cells provided extensive and long-term muscle regeneration in mice suffering from muscular dystrophy and improved their function.
To achieve these results, the scientists genetically modified two well-studied human iPS cell lines and a line of human embryonic stem cells with the PAX7 genome. This allowed them to regulate the levels of Pax7 protein, which is necessary for the regeneration of skeletal muscle tissue after its damage. The researchers found that such regulation stimulates the differentiation of naive ES and iPS cells into muscle-forming cells. Thus, the PAX7 gene – introduced at exactly the right time – helped determine the fate of human ES and iPS cells, "pushing" them to differentiate into muscle progenitor cells.
As soon as the researchers were able to accurately determine the optimal timing of differentiation, the cells became fully suitable for the resumption of muscle growth necessary for the treatment of diseases such as muscular dystrophy. Moreover, Pax7-induced progenitor cells proved to be much more effective in improving muscle function than human myoblasts, which, as already conducted clinical trials have shown, do not persist after transplantation.
According to John Wagner, MD, Scientific director of Clinical Research at the Stem Cell Institute U of M, this work is a phenomenal breakthrough. "Dr. Perlingeiro and her colleagues managed to overcome one of the most significant obstacles to stem cell treatment of children with devastating and life-threatening muscular dystrophy."
According to Dr. Perlingeiro, before proceeding to clinical trials, it is necessary to investigate alternative methods of administration of PAX7. Their method of delivering the Pax7 protein consists in the genetic modification of cells by viruses, and since viruses sometimes cause mutations, clinical trials are quite risky. But the researchers have set themselves the task of developing a safe and effective protocol, and are now actively engaged in testing alternative methods of gene delivery.
Portal "Eternal youth" http://vechnayamolodost.ru21.05.2012