Human adipose-derived stromal/stem cells demonstrate short-lived persistence after implantation in both an immunocompetent and an immunocompromised murine model.
Human adipose-derived stromal/stem cells demonstrate short-lived persistence after implantation in both an immunocompetent and an immunocompromised murine model.
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DOI：
10.1186/scrt532
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发表时间：
2014-12-18
影响因子：
7.5
通讯作者：
Katz AJ
中科院分区：
文献类型：
--
作者：
Agrawal H;Shang H;Sattah AP;Yang N;Peirce SM;Katz AJ
间充质细胞正在成为一种有前景的细胞再生治疗平台。然而，细胞移植后的命运在许多不同的疾病环境和组织床仍然不清楚。在这项研究中，用一种膜染料对人脂肪源性基质/干细胞（ASCs）进行荧光标记，并将其注射到免疫正常和免疫功能低下的小鼠品系中。细胞以单细胞悬浮液或自组装球体的形式注射。与此同时，细胞在注射前有目的地失活，然后以随机方式植入另一侧。包括这些“对照组”，以确定荧光膜染料是否在使用无活细胞的情况下仍能定位在注射部位。在体内递送后的第3、10和21天采集细胞植入物和周围组织，并进行盲法评估。用荧光显微镜分析注射部位，用PCR检测人特异性内源性逆转录病毒（ERV-3）定量测定人细胞数量。巨噬细胞免疫荧光染色评价宿主反应。ERV-3定量显示，在3周的时间点上，95%的人细胞在注射时是活的。尽管荧光信号在整个研究期间持续存在，但进一步的分析表明，该信号大部分位于宿主巨噬细胞内。这些结果表明，即使注射到免疫功能低下的小鼠体内，人类ASCs也能存活不到三周，这对人类ASCs具有免疫特权并能够在异种和/或同种异体模型中存活较长时间的观点提出了质疑。
Mesenchymal cells are emerging as a promising cell platform for regenerative therapies. However, the fate of cells after transplantation in many different disease settings and tissue beds remains unclear. In this study, human adipose-derived stromal/stem (ASCs) cells were fluorescently labeled with a membrane dye and injected into both immunocompetent and immunocompromised mouse strains. Cells were injected either as single cell suspensions, or as self-assembling spheroids. In parallel, cells were purposefully devitalized prior to injection and then implanted in the opposite side in a randomized fashion. These ‘control’ groups were included to determine whether the fluorescent membrane dye would remain localized at the injection site despite the use of nonviable cells. Cell implants and the surrounding tissues were harvested on days 3, 10 and 21 after in vivo delivery and evaluated in a blinded manner. Injection sites were analyzed by fluorescent microscopy, and human cell numbers were quantified using PCR detection of a human-specific endogenous retrovirus (ERV-3). Host response was evaluated by immunofluorescent staining of macrophages. ERV-3 quantification showed that 95% of the human cells that were viable when they were injected were undetectable at the three-week time-point. Although fluorescent signal persisted for the entire study period, further analysis revealed that much of this signal was located within host macrophages. These results suggest that human ASCs survive for less than three weeks after injection into even immunocompromised mice, and call into question the notion that human ASCs are immuno-privileged and capable of surviving for extended periods in xenogeneic and/or allogeneic models.
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影响因子：
4.3
作者：
Lequeux, Charlotte;Oni, Georgette;Brown, Spencer A.
通讯作者：
Brown, Spencer A.
影响因子：
4.5
作者：
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影响因子：
2.6
作者：
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影响因子：
1.5
作者：
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通讯作者：
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影响因子：
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作者：
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