Muse Cells – The Future Of Stroke Therapy?

Stem cells are pretty amazing. Adult stem cells act as a sort of biological maintenance and repair system. These cells can differentiate and specialize such as to replenish our tissues with all the types of cells found therein. The ability to control their fate is one of the most desired achievements in science.

Adult stem cells can be obtained from the bone marrow, adipose tissue or the blood. But adult human stem cells are generally considered to have a limited range of cell types into which they can differentiate, based on the tissue in which they exist. One of the biggest goals of stem cell research has been to find ways to increase the potency of adult human stem cells, i.e., their capacity to differentiate into as many different cell types as possible.

Some stem cells have been shown to be able to differentiates into different types of cells from the same of from close developmental lineages, at least in certain conditions. This means that those cells can overcome the tissue-specific restrictions and become other types of cells, being therefore what is deemed as multipotent cells.

Early in embryonic development, three germ layers are formed that originate different types of organs and tissues. This is the first big “commitment” step for stem cells. Broadly put, whereas multipotent stem cells can originate different types of cells that are derived from each one of these germ layers, pluripotent stem cells can generate cells from different developmental lineages, i.e. nearly all cells found in our body.

A huge accomplishment would be to discover a simple and effective method of turning human adult stem cells into pluripotent stem cells, making their potential applications tremendous.

A few years ago, in 2010, a research group from Japan described a distinct type of stem cells with some of those characteristics. They were multipotent cells expressing some signs of pluripotency, with the ability to self-renew and, importantly, to differentiate into cells representative of all three embryonic germ layers.

They were named multilineage-differentiating stress-enduring (Muse) cells and they were promising. The same group later showed that Muse cells could selectively generate induced pluripotent stem cells – even better. What also made them great was that they were easy to isolate since they could be extracted, for example, from populations of skin fibroblasts. Importantly, these cells did not form teratomes – tumors with components derived from different tissues or organs- very common when using both embryonic and other induced pluripotent stem cells.

One of the cell types which Muse cells are able to generate are neuronal cells. Some interesting applications for these cells are now emerging and they are rather promising, particularly in the field of stroke rehabilitation. Some animal studies have shown that Muse cells can contribute to functional recovery after ischemic stroke.

One of those studies showed that the transplantation of human Muse cells to mice with ischemic stroke could lead to motor function recovery after a few weeks; Muse cells were integrated into peri-infarct areas of the cerebral cortex and differentiated into neuronal cells.

In another study, it was observed that Muse cells spontaneously committed to a neuronal lineage when co-cultured with stroke brain slices. When transplanted into the cerebral cortex of stroke rats, Muse cells induced significant improvements in neurological and motor functions. They differentiated into neuronal cells and integrated into the sensory-motor cortex, extending their branches into the cervical region of the spinal cord.

Muse cells are unique among stem cells because they can efficiently differentiate into neuronal cells after integration in the brain, possibly reconstructing the neuronal tissue to mitigate stroke symptoms. Human fibroblast-derived Muse cells pose as a new source of transplantable stem cells, circumventing the need for gene manipulations.

These findings are highly promising: they show that Muse cells may potentially contribute to a more effective tissue regeneration and functional recovery after stroke. Let’s hope they have the same effect in humans.


Kuroda Y, Wakao S, Kitada M, Murakami T, Nojima M, & Dezawa M (2013). Isolation, culture and evaluation of multilineage-differentiating stress-enduring (Muse) cells. Nature protocols, 8 (7), 1391-415 PMID: 23787896

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Simerman AA, Dumesic DA, & Chazenbalk GD (2014). Pluripotent muse cells derived from human adipose tissue: a new perspective on regenerative medicine and cell therapy. Clinical and translational medicine, 3 PMID: 24940477

Uchida H, Morita T, Niizuma K, Kushida Y, Kuroda Y, Wakao S, Sakata H, Matsuzaka Y, Mushiake H, Tominaga T, Borlongan CV, & Dezawa M (2015). Transplantation of Unique Subpopulation of Fibroblasts, Muse Cells, Ameliorates Experimental Stroke Possibly Via Robust Neuronal Differentiation. Stem cells (Dayton, Ohio) PMID: 26388204

Wakao S, Kitada M, Kuroda Y, Shigemoto T, Matsuse D, Akashi H, Tanimura Y, Tsuchiyama K, Kikuchi T, Goda M, Nakahata T, Fujiyoshi Y, & Dezawa M (2011). Multilineage-differentiating stress-enduring (Muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts. Proceedings of the National Academy of Sciences of the United States of America, 108 (24), 9875-80 PMID: 21628574

Yamauchi T, Kuroda Y, Morita T, Shichinohe H, Houkin K, Dezawa M, & Kuroda S (2015). Therapeutic effects of human multilineage-differentiating stress enduring (MUSE) cell transplantation into infarct brain of mice. PloS one, 10 (3) PMID: 25747577

Image via Marioner / Shutterstock.

Sara Adaes, PhD

Sara Adaes, PhD, has been a researcher in neuroscience for over a decade. She studied biochemistry and did her first research studies in neuropharmacology. She has since been investigating the neurobiological mechanisms of pain at the Faculty of Medicine of the University of Porto, in Portugal. Follow her on Twitter @saradaes
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