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人脐带华通氏胶间充质干细胞分泌组对白血病细胞系具有抗增殖作用,并与阿霉素联合产生相加性细胞毒性作用。

Human Wharton's jelly mesenchymal stem cell secretome display antiproliferative effect on leukemia cell line and produce additive cytotoxic effect in combination with doxorubicin.

作者信息

Hendijani Fatemeh, Javanmard Shaghayegh Haghjooy, Sadeghi-aliabadi Hojjat

机构信息

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.

Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Tissue Cell. 2015 Jun;47(3):229-34. doi: 10.1016/j.tice.2015.01.005. Epub 2015 Jan 31.

DOI:10.1016/j.tice.2015.01.005
PMID:25779671
Abstract

Mesenchymal stem cell (MSC) therapy moves toward clinic progressively. Recent evidences establish anticancer effect of mesenchymal stem cells. However multiple factors including type of cancer, MSC source, study design, and animal model play role in final outcome. Wharton's jelly - a newly approved source of MSCs - possesses superiorities to bone marrow as the conventional source; therefore investigation of its medical effects can produce beneficial results. In this survey we examined cytotoxic and proapoptotic effect of human Wharton's jelly MSC secretome on K562 human leukemia cells. MSCs were isolated from human Wharton's jelly of umbilical cord by explant culture method, then characterized according to ISCT criteria (morphology and plastic adherence, surface antigenicity and differentiation potential). MSC secretome was collected and its cytotoxic and proapoptotic effects on K562 cells in combination with doxorubicin were evaluated using BrdU cell proliferation assay and Annexin V-PI staining. Our results showed antiproliferative effect of mesenchymal stem cell secretome on K562 cancer cells, the effect was also added to cytotoxic effect of doxorubicin without induction of drug resistance. Human Wharton's jelly derived mesenchymal stem cells exerted cytotoxic effect on leukemia cells. Addition of that effect to anticancer effect of chemotherapeutic agents can leads to cytotoxic drug dose reduction and diminished side effects.

摘要

间充质干细胞(MSC)疗法正逐步走向临床应用。近期证据证实了间充质干细胞的抗癌作用。然而,包括癌症类型、MSC来源、研究设计和动物模型等多种因素会对最终结果产生影响。沃顿胶——一种新获批的MSC来源——相较于传统来源的骨髓具有优势;因此,对其医学效果进行研究可能会产生有益成果。在本研究中,我们检测了人脐带沃顿胶MSC分泌组对K562人白血病细胞的细胞毒性和促凋亡作用。通过组织块培养法从人脐带沃顿胶中分离出间充质干细胞,然后根据国际细胞治疗协会(ISCT)标准(形态学和贴壁生长特性、表面抗原性及分化潜能)进行鉴定。收集MSC分泌组,并使用BrdU细胞增殖试验和膜联蛋白V-碘化丙啶(Annexin V-PI)染色评估其与阿霉素联合作用时对K562细胞的细胞毒性和促凋亡作用。我们的结果表明,间充质干细胞分泌组对K562癌细胞具有抗增殖作用,该作用还增强了阿霉素的细胞毒性且未诱导耐药性。人脐带沃顿胶来源的间充质干细胞对白血病细胞具有细胞毒性作用。将该作用与化疗药物的抗癌作用相加,可降低细胞毒性药物剂量并减少副作用。

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Human Wharton's jelly mesenchymal stem cell secretome display antiproliferative effect on leukemia cell line and produce additive cytotoxic effect in combination with doxorubicin.人脐带华通氏胶间充质干细胞分泌组对白血病细胞系具有抗增殖作用,并与阿霉素联合产生相加性细胞毒性作用。
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Differential expression of cell cycle and WNT pathway-related genes accounts for differences in the growth and differentiation potential of Wharton's jelly and bone marrow-derived mesenchymal stem cells.细胞周期和WNT信号通路相关基因的差异表达导致了脐带来源间充质干细胞与骨髓来源间充质干细胞在生长和分化潜能上的差异。
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Human umbilical cord Wharton's jelly mesenchymal stem cells do not transform to tumor-associated fibroblasts in the presence of breast and ovarian cancer cells unlike bone marrow mesenchymal stem cells.人脐带华通氏胶间充质干细胞在乳腺癌和卵巢癌细胞存在的情况下不会转化为肿瘤相关成纤维细胞,而骨髓间充质干细胞则会。
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