mRNA-engineered mesenchymal stromal cells expressing CXCR2 enhances cell migration and improves recovery in IBD
| Autor: | Yanwen Peng, Jieying Chen, Jie Ren, Weiqiang Li, Yu-Fan Lian, Xinqiang Lai, Xiaoran Zhang, Yiwen Deng, Bowen Zheng, Andy Peng Xiang, Tao Wu, Qiao-Jia Li, Chen Qiu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
CXCR2
business.industry Mesenchymal stem cell IBD Cell migration CXCL5 RM1-950 Gene delivery CXCL2 sema7A Chemokine receptor Drug Discovery Cancer research Molecular Medicine Medicine Original Article CXC chemokine receptors Therapeutics. Pharmacology business mesenchymal stromal cells Homing (hematopoietic) |
| Zdroj: | Molecular Therapy: Nucleic Acids, Vol 26, Iss, Pp 222-236 (2021) Molecular Therapy. Nucleic Acids |
| ISSN: | 2162-2531 |
| Popis: | Summary Mesenchymal stromal cells (MSCs) have shown significant heterogeneity in terms of therapeutic efficacy for inflammatory bowel disease (IBD) treatment, which may be due to an insufficient number of MSCs homing to the damaged tissue of the colon. Engineering MSCs with specific chemokine receptors can enhance the homing ability by lentiviral transduction. However, the unclear specific chemokine profile related to IBD and the safety concerns of viral-based gene delivery limit its application. Thus, a new strategy to modify MSCs to express specific chemokine receptors using mRNA engineering is developed to evaluate the homing ability of MSCs and its therapeutic effects for IBD. We found that CXCL2 and CXCL5 were highly expressed in the inflammatory colon, while MSCs minimally expressed the corresponding receptor CXCR2. Transient expression of CXCR2 in MSC was constructed and exhibited significantly enhanced migration to the inflamed colons, leading to a robust anti-inflammatory effect and high efficacy. Furthermore, the high expression of semaphorins7A on MSCs were found to induce the macrophages to produce IL-10, which may play a critical therapeutic role. This study demonstrated that the specific chemokine receptor CXCR2 mRNA-engineered MSCs not only improves the therapeutic efficacy of IBD but also provides an efficient and safe MSC modification strategy. Graphical abstract Li et al. demonstrate that mRNA-engineered MSCs with CXCR2 significantly increase their migratory properties to injured organ/tissue in an inflammatory bowel mouse model. This strategy for enhancing targeted stem/progenitor cell homing may provide a potential strategy to improve the efficacy of MSC-based therapeutics and be applicable to clinical patients. |
| Databáze: | OpenAIRE |
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