Rachakatla R S, Marini F, Weiss M L, Tamura M, Troyer D
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506-5602, USA.
Cancer Gene Ther. 2007 Oct;14(10):828-35. doi: 10.1038/sj.cgt.7701077. Epub 2007 Jun 29.
Umbilical cord matrix stem (UCMS) cells are unique stem cells derived from Wharton's jelly, which have been shown to express genes characteristic of primitive stem cells. To test the safety of these cells, human UCMS cells were injected both intravenously and subcutaneously in large numbers into severe combined immunodeficiency (SCID) mice and multiple tissues were examined for evidence of tumor formation. UCMS cells did not form gross or histological teratomas up to 50 days posttransplantation. Next, to evaluate whether UCMS cells could selectively engraft in xenotransplanted tumors, MDA 231 cells were intravenously transplanted into SCID mice, followed by intravenous transplantation of UCMS cells 1 and 2 weeks later. UCMS cells were found near or within lung tumors but not in other tissues. Finally, UCMS cells were engineered to express human interferon beta--designated 'UCMS-IFN-beta'. UCMS-IFN-beta cells were intravenously transplanted at multiple intervals into SCID mice bearing MDA 231 tumors and their effect on tumors was examined. UCMS-IFN-beta cells significantly reduced MDA 231 tumor burden in SCID mouse lungs indicated by wet weight. These results clearly indicate safety and usability of UCMS cells in cancer gene therapy. Thus, UCMS cells can potentially be used for targeted delivery of cancer therapeutics.
脐带基质干细胞（UCMS细胞）是源自华通氏胶的独特干细胞，已证明其表达原始干细胞的特征性基因。为了测试这些细胞的安全性，将大量人UCMS细胞静脉内和皮下注射到严重联合免疫缺陷（SCID）小鼠体内，并检查多个组织是否有肿瘤形成的迹象。移植后50天内，UCMS细胞未形成肉眼可见或组织学上的畸胎瘤。接下来，为了评估UCMS细胞是否能选择性地植入异种移植肿瘤中，将MDA 231细胞静脉内移植到SCID小鼠体内，1周和2周后再静脉内移植UCMS细胞。在肺肿瘤附近或内部发现了UCMS细胞，但在其他组织中未发现。最后，对UCMS细胞进行基因工程改造，使其表达人干扰素β，命名为“UCMS-IFN-β”。将UCMS-IFN-β细胞在多个时间点静脉内移植到携带MDA 231肿瘤的SCID小鼠体内，并检查其对肿瘤的影响。以湿重表示，UCMS-IFN-β细胞显著降低了SCID小鼠肺中MDA 231肿瘤的负荷。这些结果清楚地表明UCMS细胞在癌症基因治疗中的安全性和可用性。因此，UCMS细胞有可能用于癌症治疗药物的靶向递送。
