Effect of the extracellular component of bone marrow mesenchymal stromal cells from healthy donors on hematologic neoplasms and their angiogenesis
Effect of the extracellular component of bone marrow mesenchymal stromal cells from healthy donors on hematologic neoplasms and their angiogenesis
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DOI：
10.1007/s13577-020-00332-y
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发表时间：
2020-04-12
期刊：
影响因子：
4.3
通讯作者：
Ohyashiki, Kazuma
中科院分区：
文献类型：
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作者：
Gladkova, Nina;Umezu, Tomohiro;Ohyashiki, Kazuma
来自健康供体的骨髓间充质干细胞（BM-MSCs）是一种有前途的细胞治疗来源。然而，它们在癌症中的有效性仍然鲜为人知。这项研究是第一次评估从年轻和老年健康志愿者（KNT细胞）获得的BM-MSCs的质量。KNT细胞具有正常核型，MSC标志物（CD 90、CD 73、CD 105）呈阳性。当在适当的条件下培养时，它们表现出成脂或成骨潜力。因此，使用几种肿瘤细胞（三种多发性骨髓瘤、三种髓性白血病和三种淋巴瘤细胞系）验证了来自KNT细胞的分泌因子[上清液或细胞外囊泡（EV）]的抗肿瘤作用。来自年轻健康供体的KNT细胞的条件培养基（CM），但不是EV，显著抑制骨髓瘤和淋巴瘤细胞增殖，但增强髓性白血病增殖。来自年轻KNT的CM和EV对血液肿瘤诱导的血管生成的抗血管生成作用是明显的，并且在CM中比在EV中更突出，但在老年KNT衍生的EV中不明显。这些发现表明KNT细胞的抗肿瘤作用取决于血液肿瘤的类型，其中元素存在于上清液中而不是EV中。因此，BM-MSC可能产生影响肿瘤细胞增殖的可溶性因子，引起细胞间通讯。KNT细胞的抗血管生成作用取决于BM-MSC供体的年龄。
Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors are a promising source of cell therapy. However, their effectiveness in cancer remains less known. This study is the first to evaluate the quality of BM-MSCs obtained from young and elderly healthy volunteers (KNT cells). The KNT cells had normal karyotypes and were positive for MSC markers (CD90, CD73, CD105). When cultured under appropriate conditions, they showed adipogenic or osteogenic potential. Hence, the anti-neoplastic effects of secretory factors [supernatant or extracellular vesicles (EV)] from KNT cells were verified using several neoplastic cells (three multiple myeloma, three myeloid leukemia, and three lymphoma cell lines). The conditioned medium (CM), but not EV, of KNT cells derived from young healthy donors significantly inhibited myeloma and lymphoma cell proliferation, but enhanced myeloid leukemia proliferation. Anti-angiogenesis effect of CM and EV derived from young KNT against hematologic neoplasia-induced angiogenesis was evident and more prominent in CM than in EV but not evident in elderly KNT-derived EV. These findings indicate that the anti-tumor effect of KNT cells depends on the types of hematologic neoplasia, with elements existing in the supernatant and not in EVs. Therefore, BM-MSC may produce soluble factors that affect cell proliferation of neoplasia, causing cell-to-cell communication. The anti-angiogenesis effect of KNT cells depends on the age of BM-MSC donors.