Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites.
Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites.
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DOI：
10.3390/bioengineering10091049
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发表时间：
2023-09-06
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在再生医学中，实验动物模型通常用于研究人类细胞作为候选治疗药物的潜在效果。尽管一些研究将某些细胞（例如间充质基质细胞（MSC）或人原代细胞）描述为低免疫原性，因此无法引发强烈的炎症宿主反应，但其他研究报告了异种移植后的抗体形成和免疫排斥。因此，我们研究的目的是测试人诱导多能干细胞 (iPSC) 衍生的间充质干细胞 (iMSC) 和原代髓核细胞 (NPC) 在异种移植到免疫功能低下的裸鼠和免疫功能正常的 Sprague Dawley (SD) 大鼠的免疫豁免膝关节（14 天）和椎间盘（IVD；7 天）后的细胞保留和存活率。在这两个实验结束时，我们可以证明，通过 ELISA 评估，两种大鼠类型的全身性 IL-6 和 IgM 炎症标记物水平相对较低。此外，两种大鼠类型之间回收的细胞数量没有显着差异。总之，我们的结果表明，与免疫功能低下的大鼠相比，将人 iMSC 和 NPC 异种注射到免疫豁免的膝关节和 IVD 部位并不会导致免疫功能正常的大鼠炎症反应升高。因此，免疫功能正常的大鼠代表适合针对免疫豁免位点的异种移植研究的动物。
In regenerative medicine, experimental animal models are commonly used to study potential effects of human cells as therapeutic candidates. Although some studies describe certain cells, such as mesenchymal stromal cells (MSC) or human primary cells, as hypoimmunogenic and therefore unable to trigger strong inflammatory host responses, other studies report antibody formation and immune rejection following xenotransplantation. Accordingly, the goal of our study was to test the cellular retention and survival of human-induced pluripotent stem cell (iPSCs)-derived MSCs (iMSCs) and primary nucleus pulposus cells (NPCs) following their xenotransplantation into immune-privileged knee joints (14 days) and intervertebral discs (IVD; 7 days) of immunocompromised Nude and immunocompetent Sprague Dawley (SD) rats. At the end of both experiments, we could demonstrate that both rat types revealed comparably low levels of systemic IL-6 and IgM inflammation markers, as assessed via ELISA. Furthermore, the number of recovered cells was with no significant difference between both rat types. Conclusively, our results show that xenogeneic injection of human iMSC and NPC into immunoprivileged knee and IVD sites did not lead to an elevated inflammatory response in immunocompetent rats when compared to immunocompromised rats. Hence, immunocompetent rats represent suitable animals for xenotransplantation studies targeting immunoprivileged sites.
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影响因子：
9.7
作者：
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11.4
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影响因子：
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