Cell Physiology Laboratory, Institute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye Shosse, 76a, 123007 Moscow, Russia.
Cell Physiology Laboratory, Institute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye Shosse, 76a, 123007 Moscow, Russia.
Eur J Cell Biol. 2020 Apr;99(2-3):151069. doi: 10.1016/j.ejcb.2020.151069. Epub 2020 Jan 14.
Adipose-tissue derived stromal cells (ASCs) are currently considered as a full value alternative source of bone marrow MSCs for prevention of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation due to their immunosuppressive potential. Besides, ASCs are known to support ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs). Ex vivo expansion enables to amplify significantly the number of HSPCs of different commitment. Mononuclear cells (MNCs) from cord blood (cb) contain HSPCs and are easily assessed. The rarity of those HSPCs is a serious limitation of its application in cell therapy. Here we expanded cbMNCs in stroma-dependent setting to generate heterocellular associates consisting of ASCs and undifferentiated and low committed hematopoietic cbHSPCs. A part of cbHSPCs in associates demonstrated a primitive phenotype confirmed by formation of "cobblestone areas". ASCs associated with cbHSPCs demonstrated up-regulation of immunosuppressive indoleamine 2,3-dioxygenase (IDO), leukemia inhibitory factor (LIF), cyclooxygenase-2 (PTGS2) genes. ASC-cbHSPCs as well as ASCs provoked the suppression of HLA-DR activation and apoptosis of mitogen-stimulated T cells. VEGF transcription and secretion were elevated providing stimulation of blood vessel formation in ovo. Thus, ASCs retain immunosuppressive and proangiogenic capacities evidencing "third party" potential along with the effective support of ex vivo expansion of cbHSPCs. Above functions expand the relevance of ASCs for needs of regenerative medicine.
脂肪组织来源的基质细胞（ASCs）目前被认为是骨髓间充质干细胞（MSCs）的完全替代来源，可用于预防造血干细胞移植后移植物抗宿主病（GVHD），因为它们具有免疫抑制潜力。此外，ASCs 已知可支持造血干细胞和祖细胞（HSPCs）的体外扩增。体外扩增可显著扩增不同定向的 HSPCs 的数量。脐带血（cb）中的单核细胞（MNCs）含有 HSPCs，且易于评估。这些 HSPCs 的稀有性是其在细胞治疗中应用的严重限制。在此，我们在基质细胞依赖性环境中扩增 cbMNCs，以生成由 ASC 和未分化的低定向造血 cbHSPCs 组成的异细胞相关物。部分 cbHSPCs 在相关物中表现出原始表型，这通过形成“鹅卵石区域”得到证实。与 cbHSPCs 相关的 ASC 表现出免疫抑制吲哚胺 2,3-双加氧酶（IDO）、白血病抑制因子（LIF）、环氧化酶-2（PTGS2）基因的上调。ASC-cbHSPCs 以及 ASC 可引发 HLA-DR 激活的抑制和有丝分裂原刺激的 T 细胞凋亡。VEGF 转录和分泌增加，为鸡胚中的血管形成提供刺激。因此，ASCs 保留免疫抑制和促血管生成能力，证明了其与 cbHSPCs 的体外扩增有效支持一起具有“第三方”潜力。上述功能扩展了 ASCs 对再生医学需求的相关性。
