Stem cell transplantation aimed at neural repair following stroke has, for several years, been recognized as a possible way to ameliorate the effects of stroke. However, studies with a variety of stem cell types have shown that there are drawbacks and consequences to most stem cells tested in laboratory studies, such as the propensity for the cells to differentiate into several cell types (pluripotent) and to form tumors.
Now, a team of American and Japanese researchers has found that when rats modeled with stroke are treated with a newly discovered kind of cell called "Muse (multilineage-differentiating stress-enduring) cells," neuronal regeneration resulted in "significant improvements in neurological and motor functions" compared to control groups that were not transplanted with Muse cells. More good news is that the Muse cells, unlike many other pluripotent cells, do not cause tumors.
The study has considerable implications for future clinical studies aimed at regenerating neurological and motor function in patients who have suffered ischemic stroke.
The paper describing the study appears in the journal Stem Cells.
"Muse cells are unique stem cells that are able to self-renew and also display high efficiency for differentiating into neuron-like cells," explained lead author Dr. Cesar V Borlongan, Distinguished Professor and Vice-Chairman for Research at the University of South Florida (USF) College of Medicine Department of Neurosurgery and Brain Repair and Director of USF's the Center of Excellence for Aging and Brain Repair. "Unlike mesenchymal stem cells (MSCs) that have previously been used in stem cell transplantation in stroke-related clinical trials, in the present study Muse cells were found to possess functional characteristics of neurons as they attain the attributes of the host microenvironment. When Muse cells were transplanted into to the brains of rats modeled with stroke, they attained neuronal characteristics."
Muse cells reside in a variety of tissues, including bone marrow, skin and fat tissues. Since these cells can be derived from dermal fibroblasts (a type of connective tissue cell that provides the structural framework for animal tissues and plays a critical role in wound healing), they can be obtained with relative ease, without the need for invasive procedures required for obtaining other kinds of stem cells. Furthermore, while many stem cells used in stem cell transplantation studies have been found to cause cancer (oncogenic), Muse cells do not produce tumors (non-tumorigenic) and exhibit exceptional tissue repair potential when introduced into the blood stream.
According to the researchers, fetal stem cells may appear to be better candidates for replacing lost neural circuitry, considering that they preferentially differentiate toward being neuronal cells. However, fetal stem cell accessibility is limited and, like embryonic stem cells, their immaturity may present safety issues, such as tumor development. Also, the use of fetal and embryonic stem cells has been the topic of many ethical debates. Since Muse cells can be derived from adult tissue rather than fetal or embryonic tissue, the ethical quandaries associated with stem cell therapy may be considerably allayed with their use.
Not only do Muse cells also have the practical advantage of being non-tumorigenic, they are readily accessed commercially and can also be easily collected from patient skin biopsies. Once more, Muse cells do not have to be "induced," or genetically manipulated, to be pluripotent as required with some other cell varieties -- they already display inherent stem cell properties after isolation and, with their acquired neuronal properties, Muse cells spontaneously home toward the stroke-damaged sites.
"Ours is the first study to show that human skin fibroblast-derived Muse cells can have neuron-like function, possess an inherent ability to assume 'stemness' properties, and to readily differentiate into neural-lineage cells after integration into the stroke brain," said co-lead author Dr. Mari Dezawa, Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine in Sendai, Japan. "Our results show that Muse cells are a feasible and promising source for cell-based approaches to ischemic stroke therapy."
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Dezawa M et al. Transplantation of Unique Subpopulation of Fibroblasts, Muse Cells, Ameliorates Experimental Stroke Possibly Via Robust Neuronal Differentiation. Stem Cells, Published Online September 28 2015. doi: 10.1002/stem.2206