Rapid selection of mesenchymal stem and progenitor cells in primary prostate stromal cultures.
Rapid selection of mesenchymal stem and progenitor cells in primary prostate stromal cultures.
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DOI：
10.1002/pros.23145
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发表时间：
2016-05
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影响因子：
--
通讯作者：
Isaacs JT
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文献类型：
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作者：
Brennen WN;Kisteman LN;Isaacs JT
癌相关成纤维细胞（CAFs）是肿瘤微环境的主要组成部分，具有促肿瘤特性。尽管有这些知识，它们的生理起源仍然知之甚少。骨髓间充质干细胞（MSCs）可以用于组织损伤和炎症区域，包括前列腺癌。在临床前模型中，MSCs可以产生并具有许多与CAFs重叠的特性。用多参数流式细胞术和多能分化测定法对年轻器官供体和前列腺癌患者的原发性前列腺间质培养物与骨髓间质培养物中的间质干细胞进行了比较。在多种培养条件下，包括常氧、缺氧和各种培养基，确定群体倍增次数、群体倍增、细胞大小和分化潜力。ELISA法检测TGF-β。间充质干细胞和间质祖细胞不仅存在于正常和恶性前列腺组织中，而且很快被选择用于从这些组织中提取的原代间质培养；在短短几段时间内成为优势种群。生长势与TGF-β浓度呈负相关。所有条件下产生的群体平均细胞直径为> ~ 15 μm。所有被测试的培养物都具有成骨和软骨分化的能力，但与骨髓来源的间质干细胞不同，来源于正常前列腺组织的原代基质培养物缺乏成脂分化的潜力。相反，来自前列腺癌患者的基质培养物的一部分保留了分化为脂肪细胞的能力；这一特性在缺氧条件下在骨髓和前列腺来源的间充质干细胞中都被显著抑制。原代前列腺基质培养高度富集具有MSC或基质祖细胞表型的细胞。当考虑到它们的重叠特性时，使用诸如此类的原代培养物来研究caf会产生有趣的影响。来源于正常前列腺的间质培养缺乏脂肪形成表明它们具有谱系限制的祖细胞表型。一组前列腺癌患者培养物中脂肪形成分化的保留表明，从骨髓中积极募集较少的祖细胞或间充质干细胞是疾病进展的一个功能。这种招募可以潜在地用于预后目的或基于细胞的平台，用于将细胞毒性药物系统递送到前列腺癌部位。
Carcinoma-associated fibroblasts (CAFs) are a dominant component of the tumor microenvironment with pro-tumorigenic properties. Despite this knowledge, their physiologic origins remain poorly understood. Mesenchymal stem cells (MSCs) can be recruited from the bone marrow to areas of tissue damage and inflammation, including prostate cancer. MSCs can generate and have many overlapping properties with CAFs in preclinical models. Multiparameter flow cytometry and multipotent differentiation assays used to define MSCs in primary prostate stromal cultures derived from young (>25 yrs) organ donors and prostate cancer patients compared with bone marrow-derived stromal cultures. Population doubling times, population doublings, cell size, and differentiation potential determined under multiple culture conditions, including normoxia, hypoxia, and a variety of media. TGF-β measured by ELISA. MSCs and stromal progenitors are not only present in normal and malignant prostate tissue, but are quickly selected for in primary stromal cultures derived from these tissues; becoming the dominant population within just a few passages. Growth potential inversely associated with TGF-β concentrations. All conditions generated populations with an average cell diameter >15 μm. All cultures tested had the ability to undergo osteogenic and chondrogenic differentiation, but unlike bone marrow-derived MSCs, primary stromal cultures derived from normal prostate tissue lack adipogenic differentiation potential. In contrast, a subset of stromal cultures derived from prostate cancer patients retain the ability to differentiate into adipocytes; a property that is significantly suppressed under hypoxic conditions in both bone marrow- and prostate-derived MSCs. Primary prostate stromal cultures are highly enriched in cells with an MSC or stromal progenitor phenotype. The use of primary cultures such as these to study CAFs raises interesting implications when considering their overlapping properties. The lack of adipogenesis in stromal cultures derived from normal prostates suggests they have a lineage-restricted progenitor phenotype. The retention of adipogenic differentiation in cultures from a subset of prostate cancer patients suggests the active recruitment of less committed progenitors or MSCs from the bone marrow as a function of disease progression. This recruitment can potentially be exploited for prognostic purposes or a cell-based platform for the systemic delivery of cytotoxic agents to sites of prostate cancer.