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工程化干细胞产生具有增强骨再生效果的外泌体：基因治疗的一种替代策略。

Engineering stem cells to produce exosomes with enhanced bone regeneration effects: an alternative strategy for gene therapy.

机构信息

Research Center for Human Tissue and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.

Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 518053, China.

出版信息

J Nanobiotechnology. 2022 Mar 15;20(1):135. doi: 10.1186/s12951-022-01347-3.

DOI:10.1186/s12951-022-01347-3
PMID:35292020
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8922796/
Abstract

BACKGROUND

Exosomes derived from stem cells have been widely studied for promoting regeneration and reconstruction of multiple tissues as "cell-free" therapies. However, the applications of exosomes have been hindered by limited sources and insufficient therapeutic potency.

RESULTS

In this study, a stem cell-mediated gene therapy strategy is developed in which mediator mesenchymal stem cells are genetically engineered by bone morphogenetic protein-2 gene to produce exosomes (MSC-BMP2-Exo) with enhanced bone regeneration potency. This effect is attributed to the synergistic effect of the content derived from MSCs and the up-regulated BMP2 gene expression. The MSC-BMP2-Exo also present homing ability to the injured site. The toxic effect of genetical transfection vehicles is borne by mediator MSCs, while the produced exosomes exhibit excellent biocompatibility. In addition, by plasmid tracking, it is interesting to find a portion of plasmid DNA can be encapsulated by exosomes and delivered to recipient cells.

CONCLUSIONS

In this strategy, engineered MSCs function as cellular factories, which effectively produce exosomes with designed and enhanced therapeutic effects. The accelerating effect in bone healing and the good biocompatibility suggest the potential clinical application of this strategy.

摘要

背景

干细胞衍生的外泌体作为“无细胞”疗法，已广泛研究用于促进多种组织的再生和重建。然而，外泌体的应用受到来源有限和治疗效力不足的限制。

结果

在这项研究中，开发了一种基于干细胞的基因治疗策略，其中中介间充质干细胞通过骨形态发生蛋白 2 基因进行基因工程改造，以产生具有增强骨再生效力的外泌体（MSC-BMP2-Exo）。这种效应归因于 MSC 来源的内容和上调的 BMP2 基因表达的协同作用。MSC-BMP2-Exo 还具有归巢到损伤部位的能力。基因转染载体的毒性作用由中介间充质干细胞承担，而产生的外泌体表现出良好的生物相容性。此外，通过质粒追踪，有趣的是发现一部分质粒 DNA 可以被外泌体包裹并递送到受体细胞。

结论

在该策略中，工程化的 MSC 作为细胞工厂，有效地产生具有设计和增强治疗效果的外泌体。在骨愈合中的加速作用和良好的生物相容性表明该策略具有潜在的临床应用前景。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc98/8922796/d437be6849d2/12951_2022_1347_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc98/8922796/6b20ee93d5aa/12951_2022_1347_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc98/8922796/5af627877ce1/12951_2022_1347_Fig10_HTML.jpg

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