Journal
JOURNAL OF NANOBIOTECHNOLOGY
Volume 20, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12951-022-01347-3
Keywords
Exosomes; Stem cell; Gene therapy; Tissue regeneration; Cell-free therapy
Funding
- National Natural Science Foundation of China [81972071, 81802959]
- Guangdong Basic and Applied Basic Research Foundation [2021A1515010191, 2018A030313888]
- Science and Technology Research Funding of Shenzhen [JCYJ20210324102001003, JSGG20180507183242702, JCYJ20200109150420892]
- HKU-SZH Fund for Shenzhen Key Medical Discipline [SZXK2020084]
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A stem cell-mediated gene therapy strategy was developed in this study, where genetically engineered mesenchymal stem cells were used to produce exosomes with enhanced bone regeneration potency. These engineered exosomes exhibited homing ability to the injured site and showed potential clinical applications.
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.
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