Title:
Muse cells: Unique human mesenchymal stem cells that exist in vivo

Mari Dezawa, M.D., PhD
Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine,

Abstract:
During the study of transdifferenitation of human bone marrow stromal cells (MSCs) into neuronal cells and muscle cells, we found that naive human MSCs grown in adherent culture spontaneously form characteristic cell clusters at a very low frequency that appear similar to clusters formed by human ES cells, suggesting that naive HMSCs may contain multipotent cells. On the other hand, dormant tissue stem cells are known to be activated when tissues are exposed to stress, burdens, or damage. We explored the possibility of whether stress conditions could be exploited for a method to enrich the putative stem cells in adult human mesenchymal cell populations.
We found adult human stem cells that can generate, from a single cell, cells with the characteristics of the three germ layers. The cells are characterized as stress-tolerant stem cells and can be isolated from cultured skin fi broblasts or bone marrow stromal cells, or directly from bone marrow aspirates. They are indistinguishable from other major mesenchymal cells in adherent culture, but when they are transferred to suspension culture, they form characteristic cell clusters that are positive for pluripotency markers and exhibit self-renewal and differentiation. Furthermore, they can be ef fi ciently isolated as cells positive for both SSEA-3, a human pluripotency marker, and CD105, a mesenchymal cell marker. The cells exhibit multipotency, but their proliferation activity is not very high. Furthermore, although retaining their differentiation ability in vivo, these cells, unlike authentic ES cells, do not form teratomas in testes of immunode fi cient mice. In fact, when transplanted into immunode fi cient mice by local or i.v. injection, the cells integrated into damaged skin, muscle, or liver and differentiated into cytokeratin 14-, dystrophin-, or albumin-positive cells in the respective tissues.
Thus, non-tumorigenic stem cells with the ability to generate the multiple cell types of the three germ layers can be obtained through easily accessible adult human mesenchymal cells without introducing exogenous genes. These unique cells will be bene fi cial for cell-based therapy and biomedical research.

References:
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2. Dezawa M, Ishikawa H, Itokazu Y, Yoshihara T, Hoshino M, Takeda S, Ide C, Nabeshima Y. Bone marrow stromal cells generate muscle cells and repair muscle degeneration. Science 309(5732):314-317, 2005.

3. Yasumasa Kuroda, Masaaki Kitada, Shohei Wakao, Kouki Nishikawa, Yukihiro Tanimura, Hideki Makinoshima, Makoto Goda, Hideo Akashi, Ayumu Inutsuka, Akira Niwa, Taeko Shigemoto, Yoko Nabeshima, Tatsutoshi Nakahata, Yo-ichi Nabeshima, Yoshinori Fujiyoshi, and Mari Dezawa . Unique multipotent cells in adult human mesenchymal cell populations. PNAS 107(19):8639-43, May 11, 2010 .