Human Amniotic Fluid-Derived Mesenchymal Stem Cells As Therapeutic Vehicles: A Novel Approach For the Treatment of Bladder Cancer
Human Amniotic Fluid-Derived Mesenchymal Stem Cells As Therapeutic Vehicles: A Novel Approach For the Treatment of Bladder Cancer
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DOI：
10.1089/scd.2011.0151
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发表时间：
2012-05-01
影响因子：
4
通讯作者：
Anagnou, Nicholas P.
中科院分区：
文献类型：
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作者：
Bitsika, Vasiliki;Roubelakis, Maria G.;Anagnou, Nicholas P.
最近的研究支持以细胞为基础的癌症治疗。对于这种治疗方案来说，间充质干细胞（MSCs）是一种有利的细胞类型，它可以很容易地在培养中繁殖，通过基因修饰来表达治疗蛋白，并且在体内表现出对实体瘤的先天倾向。最近，我们成功地从妊娠中期羊水中分离并扩增了MSCs （AF-MSCs）。AF-MSCs的主要特点是在体外高效快速地扩增。在此，我们研究了AF-MSCs在膀胱肿瘤模型中向肿瘤区域运输干扰素β (IFN β)的倾向和能力。为此，我们使用之前从我们的研究中产生的T24M膀胱癌细胞系，并在免疫抑制小鼠中建立了疾病进展模型，该模型可以概括膀胱癌发生的分子事件。我们的研究结果表明，AF-MSCs在迁移到T24M细胞或T24M条件培养基时表现出高运动性，我们进一步鉴定和研究了可能触发这些增强迁移特性的分泌因子。此外，将慢病毒转导的表达绿色荧光蛋白（GFP）或IFN β的AF-MSCs以多剂量静脉注射给T24M荷瘤动物，以检验其治疗效果。GFP-和IFN - af - mscs成功迁移并定植在肿瘤部位。值得注意的是，在IFN β - af - mscs的存在下，可以显著抑制肿瘤生长并延长小鼠的存活时间。总的来说，这些结果证明了AF-MSCs作为抗癌载体的巨大潜力，通过靶向肿瘤部位实现，并进一步促进其在培养中的高增殖率和扩增效率。
Recent studies support cell-based therapies for cancer treatment. An advantageous cell type for such therapeutic schemes are the mesenchymal stem cells (MSCs) that can be easily propagated in culture, genetically modified to express therapeutic proteins, and exhibit an innate tropism to solid tumors in vivo. Recently, we successfully isolated and expanded MSCs from second-trimester amniotic fluid (AF-MSCs). The main characteristic of AF-MSCs is their efficient and rapid expansion in vitro. Herein, we investigated the AF-MSCs tropism and capability to transport interferon beta (IFN beta) to the region of neoplasia in a bladder tumor model. To this end, we used the T24M bladder cancer cell line, previously generated from our studies, and developed a disease progression model in immunosuppressed mice, that can recapitulate the molecular events of bladder carcinogenesis. Our results documented that AF-MSCs exhibited high motility, when migrated either to T24M cells or to T24M-conditioned medium, and we further identified and studied the secreted factors which may trigger these enhanced migratory properties. Further, lentivirus-transduced AF-MSCs, expressing green fluorescent protein (GFP) or IFN beta, were intravenously administered to T24M tumor-bearing animals at multiple doses to examine their therapeutic effect. GFP- and IFN beta-AF-MSCs successfully migrated and colonized at the tumor site. Notably, significant inhibition of tumor growth as well as prolonged survival of mice were observed in the presence of IFN beta-AF-MSCs. Collectively, these results document the great potential of AF-MSCs as anti-cancer vehicles, implemented by the targeting of the tumor site and further facilitated by their high proliferation rate and expansion efficiency in culture.