Safety and immune regulatory properties of canine induced pluripotent stem cell-derived mesenchymal stem cells.
Safety and immune regulatory properties of canine induced pluripotent stem cell-derived mesenchymal stem cells.
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DOI：
10.1016/j.scr.2017.11.010
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发表时间：
2017-12
影响因子：
1.2
通讯作者：
Dow S
中科院分区：
文献类型：
--
作者：
Chow L;Johnson V;Regan D;Wheat W;Webb S;Koch P;Dow S
间充质干细胞在体内表现出广泛的免疫调节活性，在体外可以抑制T细胞的增殖和树突状细胞的激活。目前，大多数临床使用的骨髓间充质干细胞来自较年轻的供者，这是由于易于获得和优越的免疫调节活性。然而，来自多个无关捐赠者的MSC的使用使得标准化研究结果和比较不同临床试验的结果变得困难。一种解决方案是使用诱导多能干细胞(IPSC)来源的MSC；因为IPSC来源的MSC具有几乎无限的增殖潜力，并在体外表现出表型稳定性。鉴于犬作为干细胞疗法临床前评估的自发性疾病模型的价值，我们研究了犬IPSC来源的MSC(IMSC)的功能特性，包括免疫调节特性和形成畸胎瘤的可能性。我们发现犬间充质干细胞下调了多能性基因的表达，并且在形态上与传统的间充质干细胞相似。重要的是，iMSC在多次传代后保持了稳定的表型，在免疫缺陷小鼠中没有形成畸胎瘤，在全身注射后也没有在狗身上诱导肿瘤形成。因此，我们得出结论，iMSC表型稳定，免疫效力强，在肿瘤形成方面是安全的，并代表了一种重要的新细胞来源，用于炎性疾病的治疗调节。
Mesenchymal stem cells (MSCs) exhibit broad immune modulatory activity in vivo and can suppress T cell proliferation and dendritic cell activation in vitro. Currently, most MSC for clinical usage are derived from younger donors, due to ease of procurement and to the superior immune modulatory activity. However, the use of MSC from multiple unrelated donors makes it difficult to standardize study results and compare outcomes between different clinical trials. One solution is the use of MSC derived from induced pluripotent stem cells (iPSC); as iPSC-derived MSC have nearly unlimited proliferative potential and exhibit in vitro phenotypic stability. Given the value of dogs as a spontaneous disease model for pre-clinical evaluation of stem cell therapeutics, we investigated the functional properties of canine iPSC-derived MSC (iMSC), including immune modulatory properties and potential for teratoma formation. We found that canine iMSC downregulated expression of pluripotency genes and appeared morphologically similar to conventional MSC. Importantly, iMSC retained a stable phenotype after multiple passages, did not form teratomas in immune deficient mice, and did not induce tumor formation in dogs following systemic injection. We concluded therefore that iMSC were phenotypically stable, immunologically potent, safe with respect to tumor formation, and represented an important new source of cells for therapeutic modulation of inflammatory disorders.
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影响因子：
64.8
作者：
Mueller, Franz-Josef;Laurent, Louise C.;Kostka, Dennis;Ulitsky, Igor;Williams, Roy;Lu, Christina;Park, In-Hyun;Rao, Mahendra S.;Shamir, Ron;Schwartz, Philip H.;Schmidt, Nils O.;Loring, Jeanne F.
通讯作者：
Loring, Jeanne F.
影响因子：
7.4
作者：
Choudhery MS;Badowski M;Muise A;Pierce J;Harris DT
通讯作者：
Harris DT
影响因子：
3.7
作者：
Gropp M;Shilo V;Vainer G;Gov M;Gil Y;Khaner H;Matzrafi L;Idelson M;Kopolovic J;Zak NB;Reubinoff BE
通讯作者：
Reubinoff BE
影响因子：
6
作者：
Chen, Yen Shun;Pelekanos, Rebecca A.;Fisk, Nicholas M.
通讯作者：
Fisk, Nicholas M.
源自人类诱导多能干细胞的间充质干细胞调节过敏性鼻炎的 T 细胞表型
影响因子：
12.4
作者：
Fu, Q. L.;Chow, Y. Y.;Xu, G.
通讯作者：
Xu, G.