Muse細胞(Multi-lineage differentiating stress enduring cell,多向分化壓力耐受細胞)是由日本東北大學出澤真理課題組於2010年發現一種內源性、無成瘤性的多能幹細胞[1]。幾乎所有不同器官來源的結締組織(如骨髓、外周血)中都有Muse細胞[2][3][4]。通常Muse細胞可從商業化的間充質細胞中分離到,如人成纖維細胞、骨髓間充質幹細胞,以及脂肪源幹細胞(adipose-derived stem cells)[5][6]。Muse細胞可自發分化或在細胞因子誘導作用下分化爲三個胚層的細胞。Muse細胞的成瘤性較低,注入新的宿主體內也不會形成腫瘤,目前的觀點認爲這是因爲該細胞的端粒酶活性較低[1]。Muse細胞同時被應用於小鼠骨骼肌退變、糖尿病性皮膚潰瘍及急性重症肝炎等模型的修復研究中,研究發現Muse細胞在損傷組織中能夠和宿主的組織順利整合,並且分別向相應胚層的細胞分化[7][8][9]。有研究利用Muse細胞修復腦動脈堵塞後,引起局部缺血的中風小鼠模型,發現Muse細胞修現可以替代丟失的神經元,整合至梗死的皮質組織中,分化為神經元標誌物表達陽性的細胞,並且有較為明顯的功能修復[10]。
當Muse細胞被放置到含有營養因子和細胞因子的培養基中進行培養時,超過百分之九十的細胞都會進行定向細胞分化。若該培養基含有肝細胞生長因子、成纖維細胞生長因子4和地塞米松的胰島素-轉鐵蛋白-亞硒酸鈉時,百分之九十以上的細胞會分化成肝細胞,並且在α-胎兒蛋白和人類白蛋白表達中呈現陽性反應。在骨或脂肪細胞的培養基中,百分之九十八以上的細胞會分化為骨鈣蛋白或油紅O陽性的細胞[11]。
Kuroda, Y.; 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.-i.; Fujiyoshi, Y.; Dezawa, M. Unique multipotent cells in adult human mesenchymal cell populations. Proceedings of the National Academy of Sciences. 2010, 107 (19): 8639–43. Bibcode:2010PNAS..107.8639K. PMC 2889306 . PMID 20421459. doi:10.1073/pnas.0911647107.
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. 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. 2011, 108 (24): 9875–80. Bibcode:2011PNAS..108.9875W. PMC 3116385 . PMID 21628574. doi:10.1073/pnas.1100816108.
Dezawa, Mari. Muse Cells Provide the Pluripotency of Mesenchymal Stem Cells: Direct Contribution of Muse Cells to Tissue Regeneration. Cell Transplantation. 2016, 25 (5): 849–61. PMID 26884346. doi:10.3727/096368916X690881.
Hori, Emiko; Hayakawa, Yumiko; Hayashi, Tomohide; Hori, Satoshi; Okamoto, Soushi; Shibata, Takashi; Kubo, Michiya; Horie, Yukio; Sasahara, Masakiyo; Kuroda, Satoshi. Mobilization of Pluripotent Multilineage-Differentiating Stress-Enduring Cells in Ischemic Stroke. Journal of Stroke and Cerebrovascular Diseases. 2016, 25 (6): 1473–81. PMID 27019988. doi:10.1016/j.jstrokecerebrovasdis.2015.12.033.
Kuroda, Yasumasa; Wakao, Shohei; Kitada, Masaaki; Murakami, Toru; Nojima, Makoto; Dezawa, Mari. Isolation, culture and evaluation of multilineage-differentiating stress-enduring (Muse) cells. Nature Protocols. 2013, 8 (7): 1391–415. PMID 23787896. doi:10.1038/nprot.2013.076.
Ogura, Fumitaka; Wakao, Shohei; Kuroda, Yasumasa; Tsuchiyama, Kenichiro; Bagheri, Mozhdeh; Heneidi, Saleh; Chazenbalk, Gregorio; Aiba, Setsuya; Dezawa, Mari. Human Adipose Tissue Possesses a Unique Population of Pluripotent Stem Cells with Nontumorigenic and Low Telomerase Activities: Potential Implications in Regenerative Medicine. Stem Cells and Development. 2014, 23 (7): 717–28. PMID 24256547. doi:10.1089/scd.2013.0473.