Muse Cells

Author(s):  
Mari Dezawa
Keyword(s):  
2021 ◽  
Vol 568 ◽  
pp. 103-109
Author(s):  
Xue Chen ◽  
Xin-Yao Yin ◽  
Ya-Yu Zhao ◽  
Chen-Chun Wang ◽  
Pan Du ◽  
...  

2019 ◽  
Vol 28 (7) ◽  
pp. 907-923 ◽  
Author(s):  
Zikuan Leng ◽  
Dongming Sun ◽  
Zihao Huang ◽  
Iman Tadmori ◽  
Ning Chiang ◽  
...  

Multilineage-differentiating stress-enduring (Muse) cells are a population of pluripotent stage-specific embryonic antigen 3 (SSEA3)+ mesenchymal stem cells first described by Mari Dezawa in 2010. Although some investigators have reported SSEA3+ mesenchymal cells in umbilical cord tissues, none have quantitatively compared SSEA3+ cells isolated from Wharton’s jelly (WJ) and the cord lining (CL) of human umbilical cords (HUCs). We separated WJ and the CL from HUCs, cultured mesenchymal stromal cells (MSCs) isolated from these two tissues with collagenase, and quantified the percentage of SSEA3+ cells over three passages. The first passage had 5.0% ± 4.3% and 5.3% ± 5.1% SSEA3+ cells from WJ and the CL, respectively, but the percentage of SSEA3+ cells decreased significantly ( P < 0.05) between P0 and P2 in the CL group and between P0 and P1 in the WJ group. Magnetic-activated cell sorting (MACS) markedly enriched SSEA3+ cells to 91.4% ± 3.2%. Upon culture of the sorted population, we found that the SSEA3+ percentage ranged from 62.5% to 76.0% in P2–P5 and then declined to 42.0%–54.7% between P6 and P9. At P10, the cultures contained 37.4% SSEA3+ cells. After P10, we resorted the cells and achieved 89.4% SSEA3+ cells in culture. The procedure for MACS-based enrichment of SSEA3+ cells, followed by expansion in culture and a re-enrichment step, allows the isolation of many millions of SSEA3+ cells in relatively pure culture. When cultured, the sorted SSEA3+ cells differentiated into embryoid spheres and survived 4 weeks after transplant into a contused Sprague-Dawley rat spinal cord. The transplanted SSEA3+ cells migrated into the injury area from four injection points around the contusion site and did not produce any tumors. The umbilical cord is an excellent source of fetal Muse cells, and our method allows the practical and efficient isolation and expansion of relatively pure populations of SSEA3+ Muse cells that can be matched by human leukocyte antigen for transplantation in human trials.


2019 ◽  
Vol 1 (1) ◽  
pp. 17-19 ◽  
Author(s):  
Shingo Minatoguchi ◽  
Takahiro Ando ◽  
Toshiki Tanaka ◽  
Yoshihisa Yamada ◽  
Hiromitsu Kanamori ◽  
...  

2020 ◽  
pp. 297-314
Author(s):  
Mari Dezawa
Keyword(s):  

2019 ◽  
Vol 6 (1) ◽  
pp. 68-72
Author(s):  
Ali M. Fouad ◽  
Mahmoud M. Gabr ◽  
Elsayed K. Abdelhady ◽  
Sahar A. Rashed ◽  
Sherry M. Khater ◽  
...  

2016 ◽  
Vol 18 (2) ◽  
pp. 67-77 ◽  
Author(s):  
Qi Liu ◽  
Ru-zhi Zhang ◽  
Di Li ◽  
Sai Cheng ◽  
Yu-hua Yang ◽  
...  

2018 ◽  
Vol 122 (8) ◽  
pp. 1069-1083 ◽  
Author(s):  
Yoshihisa Yamada ◽  
Shohei Wakao ◽  
Yoshihiro Kushida ◽  
Shingo Minatoguchi ◽  
Atsushi Mikami ◽  
...  

2015 ◽  
Vol 27 (1) ◽  
pp. 260
Author(s):  
D. A. Anzalone ◽  
D. Iuso ◽  
P. Toschi ◽  
F. Zacchini ◽  
G. E. Ptak ◽  
...  

Pluripotency is the ability of one cell to generate every cell type of the 3 germ layers, a property typically owned by embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC), with some exceptions; multilineage-differentiating stress-enduring (Muse) cells are an example. Muse cells, described as pre-existing pluripotent stem cells in mesenchymal tissues (Kuroda et al. 2010) are able to form clusters from single cells in suspension culture, express pluripotency factors and differentiate into cell types of the 3 germ layers, like ESC and iPSC. In addition, Muse cells are proposed to be the only source of cells capable to generate iPSC by current methodologies (Wakao et al. 2011). However, it is unclear whether they are normally present in adult tissue, derive from precursors stem or differentiated cells, or are induced by the in vitro conditions. In our work, we tested the hypothesis that the transition from a committed (tissue) to an uncommitted (in vitro culture) environment triggers in the cells the activation of a default gene circuitry leading to pluripotency. Adult skin fibroblasts were obtained from sheep ear biopsy (n = 3) and expanded in vitro (A) or cultured in suspension in hanging drops (B) or in nonadherent dishes (C) in MEM with 10% FBS. In a subsequent experiment, clonal expansion was attempted by culturing single suspension cells in drops of medium (D). Pluripotency was assessed analysing Oct4 and Nanog expression, using real-time PCR (mRNA) and Western blotting (protein), in cultured fibroblasts compared to whole ear biopsy (30-day-old fetus was used as positive control, CTR). Furthermore, in adherent cells (A) and in clusters obtained from suspension culture (B, C, D), Oct4 and Nanog expression was compared by immunofluorescence. We found that while in the ear biopsy not one of these pluripotency markers was expressed, in in vitro-expanded fibroblasts both mRNA and protein expression was detected; mRNA expression value (mean ± s.e.m. relative to CTR) was 0.59 ± 0.18 for Nanog and 0.2 ± 0.07 for Oct4. Moreover, fibroblasts in suspension (B, C, D) were able to form clusters [obtained from 32% (16/50) of single cells, D] similar to those normally obtained with ESC, iPSC. and Muse cells. All the clusters (B, C, D) showed a more intensive signal of Oct4 and Nanog protein compared to adherent cells by immunofluorescence. In the present work we demonstrate that adult somatic cells (skin fibroblasts) express key pluripotency factors, such as OCT4 and Nanog, in both adherent and suspension culture, after removal from the tissue (ear). We can conclude that the simple in vitro culture switches on the expression of pluripotency markers in adult somatic cells. Removal from the context of the tissue probably leads the cells to lose their tissue-specific identity and acquire a new undifferentiated one, which in an optimal condition culture could result in pluripotency. Our interpretation is that reprogramming must be an automatic, default response when differentiated cells are removed from the constraints imposed by a multicellular environment.


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