Division of Neurosurgery, Department of Clinical Sciences Lund, Skåne University Hospital, Lund Stem Cell Center, Lund, Sweden.
Department of Experimental Medical Science and Lund Stem Cell Center BMC, Lund University, Lund, Sweden.
Stem Cells Transl Med. 2021 Apr;10(4):582-597. doi: 10.1002/sctm.20-0127. Epub 2020 Dec 9.
Microglia, the immune sentinel of the central nervous system (CNS), are generated from yolk sac erythromyeloid progenitors that populate the developing CNS. Interestingly, a specific type of bone marrow-derived monocyte is able to express a yolk sac microglial signature and populate CNS in disease. Here we have examined human bone marrow (hBM) in an attempt to identify novel cell sources for generating microglia-like cells to use in cell-based therapies and in vitro modeling. We demonstrate that hBM stroma harbors a progenitor cell that we name stromal microglial progenitor (STR-MP). STR-MP single-cell gene analysis revealed the expression of the consensus genetic microglial signature and microglial-specific genes present in development and CNS pathologies. STR-MPs can be expanded and generate microglia-like cells in vitro, which we name stromal microglia (STR-M). STR-M cells show phagocytic ability, classically activate, and survive and phagocyte in human brain tissue. Thus, our results reveal that hBM harbors a source of microglia-like precursors that can be used in patient-centered fast derivative approaches.
小胶质细胞是中枢神经系统 (CNS) 的免疫哨兵,由充满发育中的 CNS 的卵黄囊红髓祖细胞产生。有趣的是,一种特定类型的骨髓来源单核细胞能够表达卵黄囊小胶质细胞特征,并在疾病中填充 CNS。在这里,我们检查了人类骨髓 (hBM),试图鉴定用于生成类小胶质细胞的新型细胞来源,以用于细胞治疗和体外建模。我们证明 hBM 基质中存在一种祖细胞,我们将其命名为基质小胶质细胞祖细胞 (STR-MP)。STR-MP 单细胞基因分析显示了共识遗传小胶质细胞特征的表达,以及在发育和 CNS 病理中存在的小胶质细胞特异性基因。STR-MP 可以在体外扩增并产生类小胶质细胞,我们将其命名为基质小胶质细胞 (STR-M)。STR-M 细胞表现出吞噬能力,经典激活,并在人脑组织中存活和吞噬。因此,我们的结果表明 hBM 蕴藏着可用于以患者为中心的快速衍生方法的类小胶质细胞前体来源。