Joyce Daniel, Fujino Masayuki, Morita Miwa, Araki Ryoko, Fung John, Qian Shiguang, Lu Lina, Li Xiao-Kang
Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA.
Laboratory of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Stem Cell Res. 2018 May;29:32-41. doi: 10.1016/j.scr.2018.03.009. Epub 2018 Mar 16.
Myeloid-derived suppressor cells (MDSCs) are markedly increased in cancer patients and tumor-bearing mice and promote tumor growth and survival by inhibiting host innate and adaptive immunity. In this study, we generated and characterized MDSCs from murine-induced pluripotent stem cells (iPSCs). The iPSCs were co-cultured with OP9 cells, stimulated with GM-CSF, and became morphologically heterologous under co-culturing with hepatic stellate cells. Allogeneic and OVA-specific antigen stimulation demonstrated that iPS-MDSCs have a T-cell regulatory function. Furthermore, a popliteal lymph node assay and autoimmune hepatitis model showed that iPS-MDSCs also regulate immune responsiveness in vivo and have a therapeutic effect against hepatitis. Taken together, our results demonstrated a method of generating functional MDSCs from iPSCs and highlighted the potential of iPS-MDSCs as a key cell therapy resource for transplantation and autoimmune diseases.
髓源性抑制细胞（MDSCs）在癌症患者和荷瘤小鼠中显著增加，并通过抑制宿主先天免疫和适应性免疫来促进肿瘤生长和存活。在本研究中，我们从小鼠诱导多能干细胞（iPSCs）中生成并鉴定了MDSCs。将iPSCs与OP9细胞共培养，用粒细胞-巨噬细胞集落刺激因子（GM-CSF）刺激，并在与肝星状细胞共培养时形态变得异质。同种异体和卵清蛋白特异性抗原刺激表明，iPS-MDSCs具有T细胞调节功能。此外，腘窝淋巴结试验和自身免疫性肝炎模型表明，iPS-MDSCs在体内也调节免疫反应性，并对肝炎具有治疗作用。综上所述，我们的结果证明了一种从iPSCs生成功能性MDSCs的方法，并突出了iPS-MDSCs作为移植和自身免疫性疾病关键细胞治疗资源的潜力。
