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移植的人诱导多能干细胞改善脊髓损伤的预后：损伤微环境的调节。

Grafted human induced pluripotent stem cells improve the outcome of spinal cord injury: modulation of the lesion microenvironment.

机构信息

Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Szeged, Kossuth Lajos sgt. 40., 6724, Szeged, Hungary.

BioTalentum Ltd., Gödöllő, Hungary.

出版信息

Sci Rep. 2020 Dec 29;10(1):22414. doi: 10.1038/s41598-020-79846-2.

DOI:10.1038/s41598-020-79846-2
PMID:33376249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7772333/
Abstract

Spinal cord injury results in irreversible tissue damage followed by a very limited recovery of function. In this study we investigated whether transplantation of undifferentiated human induced pluripotent stem cells (hiPSCs) into the injured rat spinal cord is able to induce morphological and functional improvement. hiPSCs were grafted intraspinally or intravenously one week after a thoracic (T11) spinal cord contusion injury performed in Fischer 344 rats. Grafted animals showed significantly better functional recovery than the control rats which received only contusion injury. Morphologically, the contusion cavity was significantly smaller, and the amount of spared tissue was significantly greater in grafted animals than in controls. Retrograde tracing studies showed a statistically significant increase in the number of FB-labeled neurons in different segments of the spinal cord, the brainstem and the sensorimotor cortex. The extent of functional improvement was inversely related to the amount of chondroitin-sulphate around the cavity and the astrocytic and microglial reactions in the injured segment. The grafts produced GDNF, IL-10 and MIP1-alpha for at least one week. These data suggest that grafted undifferentiated hiPSCs are able to induce morphological and functional recovery after spinal cord contusion injury.

摘要

脊髓损伤导致不可逆转的组织损伤，随后功能恢复非常有限。在这项研究中，我们研究了将未分化的人诱导多能干细胞（hiPSCs）移植到损伤的大鼠脊髓中是否能够诱导形态和功能的改善。在 Fischer 344 大鼠的 T11 脊髓挫伤损伤后一周，将 hiPSCs 经椎管内或静脉内移植。与仅接受挫伤损伤的对照组相比，移植组的动物表现出明显更好的功能恢复。形态学上，挫伤腔明显更小，移植组的保留组织量明显大于对照组。逆行示踪研究显示，脊髓的不同节段、脑干和感觉运动皮层中，FB 标记神经元的数量有统计学意义的增加。功能改善的程度与腔周围硫酸软骨素的含量以及损伤节段中的星形胶质细胞和小胶质细胞反应呈负相关。移植的细胞产生了 GDNF、IL-10 和 MIP1-alpha 至少一周。这些数据表明，移植的未分化 hiPSCs 能够诱导脊髓挫伤损伤后的形态和功能恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/212fc5a1c13d/41598_2020_79846_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/ba9df25e5392/41598_2020_79846_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/c79a5d24fe38/41598_2020_79846_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/212fc5a1c13d/41598_2020_79846_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/d36d053c6fcc/41598_2020_79846_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/4e1fdb752771/41598_2020_79846_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/ba85dc877e05/41598_2020_79846_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/342a881a17f2/41598_2020_79846_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/97a4f2677e35/41598_2020_79846_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/6b712679f58a/41598_2020_79846_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/ba9df25e5392/41598_2020_79846_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/c79a5d24fe38/41598_2020_79846_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b4e/7772333/212fc5a1c13d/41598_2020_79846_Fig9_HTML.jpg

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