Wang Y, Huso D L, Harrington J, Kellner J, Jeong D K, Turney J, McNiece I K
Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Cytotherapy. 2005;7(6):509-19. doi: 10.1080/14653240500363216.
Human mesenchymal stem cells (hMSC) have been isolated and characterized extensively for a variety of clinical applications. Yet it is unclear how the phenomenon of hMSC plasticity can be safely and reasonably exploited for therapeutic use.
We have generated mesenchymal stem cells (MSC) from normal human BM and identified a novel cell population with a transformed phenotype. This cell population was characterized by morphologic, immunophenotypic, cytogenetic analyzes and telomerase expression. Its tumorigenicity in NOD/SCID mice was also studied.
A subpopulation of cells in hMSC culture was noted to appear morphologically distinct from typical MSC. The cells were spherical, cuboidal to short spindle in shape, adherent and exhibited contact independent growth. Phenotypically the cells were CD133(+), CD34(-), CD45(-), CD90(low), CD105(-), VEGFR2(+). Cytogenetic analysis showed chromosome aneuploidy and translocations. These cells also showed a high level of telemerase activity compared with typical MSC. Upon transplantation into NOD/SCID mice, multiple macroscopic solid tumors formed in multiple organs or tissues. Histologically, these tumors were very poorly differentiated and showed aggressive growth with large areas of necrosis.
The possible explanations for the origin of this cell population are: (1) the cells represent a transformed population of MSC that developed in culture; (2) abnormal cells existed in the donor BM at rare frequency and subsequently expanded in culture. In either case, the MSC culture may provide a suitable environment for transformed cells to expand or propagate in vitro. In summary, our data demonstrate the potential of transformed cells in hMSC culture and highlight the need for karyotyping as a release criteria for clinical use of MSC.
人骨髓间充质干细胞（hMSC）已被广泛分离和鉴定，用于多种临床应用。然而，尚不清楚如何安全合理地利用hMSC可塑性现象进行治疗。
我们从正常人骨髓中生成了间充质干细胞（MSC），并鉴定出一种具有转化表型的新型细胞群体。通过形态学、免疫表型、细胞遗传学分析和端粒酶表达对该细胞群体进行了表征。还研究了其在NOD/SCID小鼠中的致瘤性。
注意到hMSC培养物中的一个细胞亚群在形态上与典型的MSC不同。这些细胞呈球形、立方形至短梭形，贴壁生长并表现出接触非依赖性生长。表型上，这些细胞为CD133(+)、CD34(-)、CD45(-)、CD90(低)、CD105(-)、VEGFR2(+)。细胞遗传学分析显示染色体非整倍性和易位。与典型的MSC相比，这些细胞还表现出高水平的端粒酶活性。移植到NOD/SCID小鼠后，多个器官或组织中形成了多个肉眼可见的实体瘤。组织学上，这些肿瘤分化很差，表现为侵袭性生长，有大片坏死。
该细胞群体起源的可能解释是：（1）这些细胞代表了在培养中发生转化的MSC群体；（2）供体骨髓中存在罕见频率的异常细胞，随后在培养中扩增。无论哪种情况，MSC培养都可能为转化细胞在体外扩增或增殖提供合适的环境。总之，我们的数据证明了hMSC培养物中转化细胞的潜力，并强调了核型分析作为MSC临床使用放行标准的必要性。
