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Effect of the extracellular component of bone marrow mesenchymal stromal cells from healthy donors on hematologic neoplasms and their angiogenesis.
Human Cell ( IF 3.4 ) Pub Date : 2020-04-12 , DOI: 10.1007/s13577-020-00332-y
Nina Gladkova 1, 2 , Tomohiro Umezu 3, 4, 5 , Satoshi Imanishi 4 , Chiaki Kawana 3 , Junko H Ohyashiki 4 , Kazuma Ohyashiki 3
Affiliation  

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.

中文翻译:

健康捐献者骨髓间充质基质细胞的细胞外成分对血液肿瘤及其血管新生的影响。

来自健康供体的骨髓间充质基质细胞(BM-MSC)是细胞疗法的有希望的来源。然而,它们在癌症中的有效性仍然鲜为人知。这项研究是第一个评估从年轻和老年健康志愿者(KNT细胞)获得的BM-MSC的质量的研究。KNT细胞具有正常的核型,并且对MSC标记(CD90,CD73,CD105)呈阳性。在适当条件下培养时,它们显示出成脂或成骨的潜力。因此,使用几种肿瘤细胞(三种多发性骨髓瘤,三种髓样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。条件培养基(CM),而不是EV,来自年轻健康供体的KNT细胞可显着抑制骨髓瘤和淋巴瘤细胞增殖,但可增强髓样白血病的增殖。年轻的KNT衍生的CM和EV对血液肿瘤形成所致血管新生的抗血管生成作用是明显的,并且在CM中比EV更显着,但在老年KNT衍生的EV中则不明显。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,其元素存在于上清液中而不存在于电动汽车中。因此,BM-MSC可能产生影响瘤形成细胞增殖的可溶性因子,从而导致细胞间的通讯。KNT细胞的抗血管生成作用取决于BM-MSC供体的年龄。年轻的KNT衍生的CM和EV对血液肿瘤形成所致血管新生的抗血管生成作用是明显的,并且在CM中比EV更显着,但在老年KNT衍生的EV中则不明显。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,其元素存在于上清液中而不存在于电动汽车中。因此,BM-MSC可能产生可溶因子,影响瘤形成的细胞增殖,从而引起细胞间的通讯。KNT细胞的抗血管生成作用取决于BM-MSC供体的年龄。年轻的KNT衍生的CM和EV对血液肿瘤形成所致血管新生的抗血管生成作用是明显的,并且在CM中比EV更显着,但在老年KNT衍生的EV中则不明显。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,其元素存在于上清液中而不存在于电动汽车中。因此,BM-MSC可能产生影响瘤形成细胞增殖的可溶性因子,从而导致细胞间的通讯。KNT细胞的抗血管生成作用取决于BM-MSC供体的年龄。上清液中存在元素,而电动汽车中不存在。因此,BM-MSC可能产生影响瘤形成细胞增殖的可溶性因子,从而导致细胞间的通讯。KNT细胞的抗血管生成作用取决于BM-MSC供体的年龄。上清液中存在元素,而电动汽车中不存在。因此,BM-MSC可能产生影响肿瘤形成的细胞增殖的可溶性因子,从而导致细胞间的通讯。KNT细胞的抗血管生成作用取决于BM-MSC供体的年龄。
更新日期:2020-04-12
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