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HSF-1 enhances cardioprotective potential of stem cells via exosome biogenesis and their miRNA cargo enrichment.
Guru, Sameer Ahmad; Saha, Progyaparamita; Chen, Ling; Tulshyan, Antariksh; Ge, Zhi-Dong; Baily, Jeanette; Simons, Lydia; Stefanowicz, Artur; Bilewska, Agata; Mehta, Vivek; Mishra, Rachana; Sharma, Sudhish; Ali, Asif; Krishnan, Swetha; Kaushal, Sunjay.
Afiliación
  • Guru SA; Deininger Lab, Versiti, Blood Research Institute, Milwaukee, WI, USA.
  • Saha P; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
  • Chen L; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
  • Tulshyan A; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
  • Ge ZD; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
  • Baily J; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
  • Simons L; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
  • Stefanowicz A; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
  • Bilewska A; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
  • Mehta V; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
  • Mishra R; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
  • Sharma S; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
  • Ali A; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
  • Krishnan S; David Pincus lab, Molecular Genetics and Cell Biology Committee on Cancer Biology, Chicago University, Chicago, IL, USA.
  • Kaushal S; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA.
Stem Cell Rev Rep ; 19(6): 2038-2051, 2023 08.
Article en En | MEDLINE | ID: mdl-37261668
Stem cell therapy provides a hope to no option heart disease patient group. Stem cells work via different mechanisms of which paracrine mechanism is reported to justify most of the effects. Therefore, identifying the control arms for paracrine cocktail production is necessary to tailor stem cell functions in disease contextual manner. In this study, we describe a novel paracrine cocktail regulatory axis, in stem cells, to enhance their cardioprotective abilities. We identified that HSF1 knockout resulted in reduced cardiac regenerative abilities of mesenchymal stem cells (MSCs) while its overexpression had opposite effects. Altered exosome biognesis and their miRNA cargo enrichment were found to be underlying these altered regenerative abilities. Decreased production of exosomes by MSCs accompanied their loss of HSF1 and vice versa. Moreover, the exosomes derived from HSF1 depleted MSCs showed significantly reduced candidate miRNA expression (miR-145, miR-146, 199-3p, 199b and miR-590) compared to those obtained from HSF1 overexpressing MSCs. We further discovered that HSF1 mediates miRNAs' enrichment into exosomes via Y binding protein 1 (YBX1) and showed, by loss and gain of function strategies, that miRNAs' enrichment in mesenchymal stem cell derived exosomes is deregulated with altered YBX1 expression. It was finally demonstrated that absence of YBX1 in MSCs, with normal HSF1 expression, resulted in significant accumulation of candidate miRNAs into the cells. Together, our data shows that HSF1 plays a critical role in determining the regenerative potential of stem cells. HSF1 does that by affecting exosome biogenesis and miRNA cargo sorting via regulation of YBX1 gene expression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Exosomas / Células Madre Mesenquimatosas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Stem Cell Rev Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Exosomas / Células Madre Mesenquimatosas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Stem Cell Rev Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos