Cutting edge Seminar

 

 

Speaker: Mari Dezawa（Professor, Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine）

 

 

Date&Time: 5 Dec. (Wed.) 2018, 12:00- 13:00

Venue: Conference Room(1F), IMEG

 

Abstract:

Multilineage-differentiating stress enduring (Muse) cells are naturally existing unique endogenous stem cells that are non-tumorigenic and are pluripotent. They express pluripotent markers, can generate cells representative of all three germ layers from a single cell and are able to self-renew. Since they express specific receptor for damage signal, sphingosine-1-phosphate (S1P) receptor2, they can preferentially home into S1P-producing damaged site after intravenous injection with lower entrapment in the lung and spleen. After integration, they replenish lost cells by spontaneous differentiation into tissue-compatible cells, leading to long lasting robust tissue and functional regeneration. The unique reparative functions of Muse cells were demonstrated in animal models of liver cirrhosis, stroke, chronic kidney disease and acute myocardial infarction (AMI) by intravenous drip. They do not have to be “induced,” or genetically manipulated, to be pluripotent or be purposive cells before administration.

They can be collected as cells positive for SSEA-3, a surface marker for pluripotent stem cells, from readily accessible sources such as the bone marrow (~0.03% of the total mononucleated cell population), and from commercially available cultured fibroblasts (several %). Recently, Muse cells are shown to circulate in peripheral blood in healthy donors, and the number increases in stroke and AMI patients in an acute phase, suggesting that endogenous Muse cells are mobilized into peripheral blood to repair tissues while their number is not sufficient to recover, and that supply of exogenous Muse cells by intravenous drip is expected to deliver statistically meaningful functional recovery. Overall, Muse cells are a feasible source for cell-based therapy, that may safely provide clinically relevant regenerative effects compatible with the ‘body’s natural repair systems’ by simple cost-effective strategy-collection of Muse cells from sources, large scale expansion and ‘intravenous drip’. Currently, the phase I clinical study targeting AMI is conducted by Life Science Institute Inc., a group company of Mitsubishi Chemical Holdings.

 

 

References:

１）Yamada Y1, Wakao S1, Kushida Y, Minatoguchi S, Mikami A, Higashi K, Baba S, Shigemoto T, Kuroda Y, Kanamori H, Amin M, Kawasaki M, Nishigaki K, Taoka M1, Isobe T, Muramatsu C, Dezawa M, Minatoguchi S. S1P–S1PR2 Axis Mediates Homing of Muse Cells Into Damaged Heart for Long-Lasting Tissue Repair and Functional Recovery After Acute Myocardial Infarction. Circ Res. 13;122(8):1069-1083, 2018.

２）Uchida H, Niizuma K, Kushida Y, Wakao S, Tominaga T, Borlongan CV, Dezawa M. Human Muse Cells Reconstruct Neuronal Circuitry in Subacute Lacunar Stroke Model. Stroke 48(2):428-435, 2017

３）Kuroda Y1, Kitada M, Wakao S, Nishikawa K, Tanimura Y, Makinoshima H, Goda M, Akashi H, Inutsuka A, Niwa A, Shigemoto T, Nabeshima Y, Nakahata T, Nabeshima Y, Fujiyoshi Y, Dezawa M. Unique multipotent cells in adult human mesenchymal cell populations. Proc Natl Acad Sci U S A. 11;107(19):8639-43, 2010

 

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