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心肌细胞衍生细胞和间充质干细胞细胞外囊泡非编码 RNA 的机制和治疗区别。

Mechanistic and therapeutic distinctions between cardiosphere-derived cell and mesenchymal stem cell extracellular vesicle non-coding RNA.

机构信息

Capricor Therapeutics, Inc., 8840 Wilshire Blvd., Beverly Hills, CA, 90211, USA.

Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA, 90048, USA.

出版信息

Sci Rep. 2021 Apr 21;11(1):8666. doi: 10.1038/s41598-021-87939-9.

DOI:10.1038/s41598-021-87939-9
PMID:33883598
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8060398/
Abstract

Cell therapy limits ischemic injury following myocardial infarction (MI) by preventing cell death, modulating the immune response, and promoting tissue regeneration. The therapeutic efficacy of cardiosphere-derived cells (CDCs) and mesenchymal stem cells (MSCs) is associated with extracellular vesicle (EV) release. Prior head-to-head comparisons have shown CDCs to be more effective than MSCs in MI models. Despite differences in cell origin, it is unclear why EVs from different adult stem cell populations elicit differences in therapeutic efficacy. Here, we compare EVs derived from multiple human MSC and CDC donors using diverse in vitro and in vivo assays. EV membrane protein and non-coding RNA composition are highly specific to the parent cell type; for example, miR-10b is enriched in MSC-EVs relative to CDC-EVs, while Y RNA fragments follow the opposite pattern. CDC-EVs enhance the Arg1/Nos2 ratio in macrophages in vitro and reduce MI size more than MSC-EVs and suppress inflammation during acute peritonitis in vivo. Thus, CDC-EVs are distinct from MSC-EVs, confer immunomodulation, and protect the host against ischemic myocardial injury and acute inflammation.

摘要

细胞疗法通过防止细胞死亡、调节免疫反应和促进组织再生来限制心肌梗死后的缺血性损伤。心脏球源性细胞 (CDC) 和间充质干细胞 (MSC) 的治疗效果与细胞外囊泡 (EV) 的释放有关。先前的头对头比较表明，在 MI 模型中，CDC 比 MSC 更有效。尽管细胞起源不同，但尚不清楚为什么来自不同成体干细胞群体的 EV 会引起治疗效果的差异。在这里，我们使用多种体外和体内测定方法比较了来自多个人类 MSC 和 CDC 供体的 EV。EV 膜蛋白和非编码 RNA 组成高度特定于亲本细胞类型；例如，miR-10b 在 MSC-EV 中相对于 CDC-EV 富集，而 Y RNA 片段则相反。CDC-EV 可增强体外巨噬细胞中的 Arg1/Nos2 比值，并比 MSC-EV 更能减少 MI 大小，并在体内急性腹膜炎期间抑制炎症。因此，CDC-EV 与 MSC-EV 不同，可发挥免疫调节作用，并保护宿主免受缺血性心肌损伤和急性炎症的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e1c/8060398/4fdaaf8deec2/41598_2021_87939_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e1c/8060398/02f3e522cdf1/41598_2021_87939_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e1c/8060398/92cf5912c551/41598_2021_87939_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e1c/8060398/8bc6453c5822/41598_2021_87939_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e1c/8060398/4fdaaf8deec2/41598_2021_87939_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e1c/8060398/02f3e522cdf1/41598_2021_87939_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e1c/8060398/92cf5912c551/41598_2021_87939_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e1c/8060398/8bc6453c5822/41598_2021_87939_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e1c/8060398/4fdaaf8deec2/41598_2021_87939_Fig4_HTML.jpg

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证据揭示：芯片肾脏研究将心肾综合征的循环细胞外囊泡与肾脏病理学联系起来。
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