{"title":"Microvesicles and exosomes isolated from murine bone marrow-derived mesenchymal stromal cells primed with p38MAPK inhibitor differentially regulate hematopoietic stem cell function.","authors":"Pallavi Budgude, Vaijayanti Kale, Anuradha Vaidya","doi":"10.1080/21691401.2025.2475095","DOIUrl":null,"url":null,"abstract":"<p><p>The signaling mechanisms active within mesenchymal stromal cells (MSCs) influence the composition of microvesicles (MVs) and exosomes (Exos) secreted by them. Previously, we showed that priming MSCs with a p38 pharmacological inhibitor (pMSCs) rejuvenates them and improves their ability to promote <i>ex vivo</i> hematopoietic stem cell (HSC) expansion. This study examined whether pMSCs exerted HSC-supportive ability via MVs (pMVs) and Exos (pExos). Our findings demonstrate distinct regulation of HSC fate by pMVs and pExos. pMVs promoted the expansion of long-term HSCs (LT-HSCs), distinguished by their robust self-renewal capacity and superior engraftment ability. In contrast, pExos facilitated expansion of short-term HSCs (ST-HSCs) with high proliferative and differentiation potential. Infusing a combination of pMVs- and pExos-expanded HSCs as a composite graft resulted in significantly higher HSC engraftment, emphasizing the synergistic interaction between LT- and ST-HSC populations. Gene expression studies, functional and phenotypic experiments showed that pMVs regulate HSC quiescence via the <i>Egr1/Cdkn1a</i> axis, while pExos control HSC proliferation via the <i>Nfya/Cdkn1a</i> axis. These findings provide insights into the molecular mechanisms underlying the differential regulation of HSC function by pMVs and pExos. It also proposes a composite graft strategy of using pMVs and pExos as \"MSC-derived biologics\" for improving the HSC transplantation success.</p>","PeriodicalId":8736,"journal":{"name":"Artificial Cells, Nanomedicine, and Biotechnology","volume":"53 1","pages":"122-137"},"PeriodicalIF":4.5000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Artificial Cells, Nanomedicine, and Biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1080/21691401.2025.2475095","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/10 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The signaling mechanisms active within mesenchymal stromal cells (MSCs) influence the composition of microvesicles (MVs) and exosomes (Exos) secreted by them. Previously, we showed that priming MSCs with a p38 pharmacological inhibitor (pMSCs) rejuvenates them and improves their ability to promote ex vivo hematopoietic stem cell (HSC) expansion. This study examined whether pMSCs exerted HSC-supportive ability via MVs (pMVs) and Exos (pExos). Our findings demonstrate distinct regulation of HSC fate by pMVs and pExos. pMVs promoted the expansion of long-term HSCs (LT-HSCs), distinguished by their robust self-renewal capacity and superior engraftment ability. In contrast, pExos facilitated expansion of short-term HSCs (ST-HSCs) with high proliferative and differentiation potential. Infusing a combination of pMVs- and pExos-expanded HSCs as a composite graft resulted in significantly higher HSC engraftment, emphasizing the synergistic interaction between LT- and ST-HSC populations. Gene expression studies, functional and phenotypic experiments showed that pMVs regulate HSC quiescence via the Egr1/Cdkn1a axis, while pExos control HSC proliferation via the Nfya/Cdkn1a axis. These findings provide insights into the molecular mechanisms underlying the differential regulation of HSC function by pMVs and pExos. It also proposes a composite graft strategy of using pMVs and pExos as "MSC-derived biologics" for improving the HSC transplantation success.
期刊介绍:
Artificial Cells, Nanomedicine and Biotechnology covers the frontiers of interdisciplinary research and application, combining artificial cells, nanotechnology, nanobiotechnology, biotechnology, molecular biology, bioencapsulation, novel carriers, stem cells and tissue engineering. Emphasis is on basic research, applied research, and clinical and industrial applications of the following topics:artificial cellsblood substitutes and oxygen therapeuticsnanotechnology, nanobiotecnology, nanomedicinetissue engineeringstem cellsbioencapsulationmicroencapsulation and nanoencapsulationmicroparticles and nanoparticlesliposomescell therapy and gene therapyenzyme therapydrug delivery systemsbiodegradable and biocompatible polymers for scaffolds and carriersbiosensorsimmobilized enzymes and their usesother biotechnological and nanobiotechnological approachesRapid progress in modern research cannot be carried out in isolation and is based on the combined use of the different novel approaches. The interdisciplinary research involving novel approaches, as discussed above, has revolutionized this field resulting in rapid developments. This journal serves to bring these different, modern and futuristic approaches together for the academic, clinical and industrial communities to allow for even greater developments of this highly interdisciplinary area.