Skip to main content
SpringerLink
Log in

HSF-1 enhances cardioprotective potential of stem cells via exosome biogenesis and their miRNA cargo enrichment

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

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.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

All the data related to this research work has been included in the manuscript.

Code availability

Not applicable.

References

  1. Liang, X., Ding, Y., Zhang, Y., Tse, H. F., & Lian, Q. (2014). Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplant., 23(9), 1045–1059. https://doi.org/10.3727/096368913X667709

    Article  PubMed  Google Scholar 

  2. Gnecchi, M., He, H., Liang, O. D., Melo, L. G., Morello, F., Mu, H., Noiseux, N., Zhang, L., Pratt, R. E., Ingwall, J. S., & Dzau, V. J. (2005). Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med., 11(4), 367–368. https://doi.org/10.1038/nm0405-367

    Article  CAS  PubMed  Google Scholar 

  3. Lee, C., Mitsialis, S. A., Aslam, M., Vitali, S. H., Vergadi, E., Konstantinou, G., Sdrimas, K., Fernandez-Gonzalez, A., & Kourembanas, S. (2012). Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation., 126(22), 2601–2611. https://doi.org/10.1161/CIRCULATIONAHA.112.114173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zhang, B., Yin, Y., Lai, R. C., Tan, S. S., Choo, A. B., & Lim, S. K. (2014). Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev., 23(11), 1233–1244. https://doi.org/10.1089/scd.2013.0479

    Article  CAS  PubMed  Google Scholar 

  5. Dostert, G., Mesure, B., Menu, P., & Velot, É. (2017). How do mesenchymal stem cells influence or are influenced by microenvironment through extracellular vesicles communication? Front Cell Dev Biol., 5, 6–6. https://doi.org/10.3389/fcell.2017.00006

    Article  PubMed  PubMed Central  Google Scholar 

  6. Raposo, G., & Stoorvogel, W. (2013). Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol., 200(4), 373–383. https://doi.org/10.1083/jcb.201211138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lai, R. C., Tan, S. S., Yeo, R. W. Y., Choo, A. B. H., Reiner, A. T., Su, Y., Shen, Y., Fu, Z., Alexander, L., Sze, S. K., & Lim, S. K. (2016). MSC secretes at least 3 EV types each with a unique permutation of membrane lipid, protein and RNA. J Extracell Ves., 5, 29828–29828. https://doi.org/10.3402/jev.v5.29828

    Article  CAS  Google Scholar 

  8. Liang, Y., Duan, L., Lu, J., Xia, J. (2021). Engineering exosomes for targeted drug delivery. Theranostics, Vol. 11, Issue 7. https://doi.org/10.7150/thno.52570

  9. Shurtleff, M.J., Temoche-Diaz, M.M., Karfilis, K.V., Ri, S., Schekman, R. (2016) Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. eLife;5:e19276. https://doi.org/10.7554/eLife.19276

  10. Yokoi, A., Villar-Prados, A., Oliphint, P.A., Zhang, J., Song, X., DeHoff, P., Morey, R., Liu, J., Roszik, J., Clise-Dwyer, K., Burks, J.K., O’Halloran, T.J., Laurent, L.C., Sood, A.K. (2019). Mechanisms of nuclear content loading to exosomes, Sci Adv; 5: eaax8849 20 November 2019

  11. Sharma, S., Mishra, R., Bigham, G. E., Wehman, B., Khan, M. M., Huichun, X., Saha, P., Goo, Y. A., Datla, S. R., Chen, L., Tulapurkar, M. E., Taylor, B. S., Yang, P., Karathanasis, S., Goodlett, D. R., & Kaushal, S. (2017). A Deep Proteome Analysis Identifies the Complete Secretome as the Functional Unit of Human Cardiac Progenitor Cells. Circ Res., 120(5), 816–834. https://doi.org/10.1161/CIRCRESAHA.116.309782

    Article  CAS  PubMed  Google Scholar 

  12. Gnecchi, M., He, H., Liang, O. D., Melo, L. G., Morello, F., Mu, H., Noiseux, N., Zhang, L., Pratt, R. E., Ingwall, J. S., & Dzau, V. J. (2005). Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med., 11, 367–368. https://doi.org/10.1038/nm0405-367

    Article  CAS  PubMed  Google Scholar 

  13. Yoon, Y. S., Wecker, A., Heyd, L., Park, J. S., Tkebuchava, T., Kusano, K., Hanley, A., Scadova, H., Qin, G., Cha, D. H., Johnson, K. L., Aikawa, R., Asahara, T., & Losordo, D. W. (2005). Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest., 115, 326–338. https://doi.org/10.1172/JCI22326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Nagaya, N., Kangawa, K., Itoh, T., Iwase, T., Murakami, S., Miyahara, Y., Fujii, T., Uematsu, M., Ohgushi, H., Yamagishi, M., Tokudome, T., Mori, H., Miyatake, K., & Kitamura, S. (2005). Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation., 112, 1128–1135. https://doi.org/10.1161/CIRCULATIONAHA.104.500447

    Article  PubMed  Google Scholar 

  15. Gnecchi, M., He, H., Noiseux, N., Liang, O. D., Zhang, L., Morello, F., Mu, H., Melo, L. G., Pratt, R. E., Ingwall, J. S., & Dzau, V. J. (2006). Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J., 20, 661–669. https://doi.org/10.1096/fj.05-5211com

    Article  CAS  PubMed  Google Scholar 

  16. Lim, S. Y., Kim, Y. S., Ahn, Y., Jeong, M. H., Hong, M. H., Joo, S. Y., Nam, K. I., Cho, J. G., Kang, P. M., & Park, J. C. (2006). The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model. Cardiovasc Res., 70, 530–542. https://doi.org/10.1016/j.cardiores.2006.02.016

    Article  CAS  PubMed  Google Scholar 

  17. Takahashi, M., Li, T. S., Suzuki, R., Kobayashi, T., Ito, H., Ikeda, Y., Matsuzaki, M., & Hamano, K. (2006). Cytokines produced by bone marrow cells can contribute to functional improvement of the infarcted heart by protecting cardiomyocytes from ischemic injury. Am J Physiol Heart Circ Physiol., 291, H886–H893. https://doi.org/10.1152/ajpheart.00142.2006

    Article  CAS  PubMed  Google Scholar 

  18. Uemura, R., Xu, M., Ahmad, N., & Ashraf, M. (2006). Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res., 98, 1414–1421. https://doi.org/10.1161/01.RES.0000225952.61196.39

    Article  CAS  PubMed  Google Scholar 

  19. Xu, M., Uemura, R., Dai, Y., Wang, Y., Pasha, Z., & Ashraf, M. (2007). In vitro and in vivo effects of bone marrow stem cells on cardiac structure and function. J Mol Cell Cardiol., 42, 441–448. https://doi.org/10.1016/j.yjmcc.2006.10.009

    Article  CAS  PubMed  Google Scholar 

  20. Caplice, N. M., & Deb, A. (2004). Myocardial-cell replacement: the science, the clinic and the future. Nat Clin Pract Cardiovasc Med., 1, 90–95.

    Article  PubMed  Google Scholar 

  21. Dimmeler, S., Zeiher, A. M., & Schneider, M. D. (2005). Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest., 115, 572–583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Melo, L. G., Pachori, A. S., Kong, D., Gnecchi, M., Wang, K., Pratt, R. E., & Dzau, V. J. (2004). Molecular and cell-based therapies for protection, rescue, and repair of ischemic myocardium: reasons for cautious optimism. Circulation., 109, 2386–2393.

    Article  PubMed  Google Scholar 

  23. Mirotsou, M., Zhang, Z., Deb, A., Zhang, L., Gnecchi, M., Noiseux, N., Mu, H., Pachori, A., & Dzau, V. (2007). Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci U S A., 104, 1643–1648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Colombo, M., Moita, C., van Niel, G., Kowal, J., Vigneron, J., Benaroch, P., Manel, N., Moita, L.F., Clotilde and Grac¸a Raposo. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. Journal of Cell Science 126, 5553–5565. https://doi.org/10.1242/jcs.128868

  25. Yingjie Wang, Lan Zhang, Yongjun Li, Lijuan Chen , Xiaolong Wang, Wei Guo a, Xue Zhang b,f , Gangjian Qin d , Sheng-hu He e , Arthur Zimmerman f , Yutao Liu f , Il-man Kim f, Neal L. Weintraub f , Yaoliang Tang f. (2015) Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium. International Journal of Cardiology 192 61–69, https://doi.org/10.1016/j.ijcard.2015.05.020.

  26. Wang, J., Faict, S., Maes, K., De Bruyne, E., Van Valckenborgh, E., Schots, R., Vanderkerken, K., & Menu, E. (2016). Extracellular vesicle cross-talk in the bone marrow microenvironment: implications in multiple myeloma. Oncotarget., 7(25), 38927–38945. https://doi.org/10.18632/oncotarget.7792

    Article  PubMed  PubMed Central  Google Scholar 

  27. Shanmuganathan, M., Vughs, J., Noseda, M., & Emanueli, C. Exosomes: Basic Biology and Technological Advancements Suggesting Their Potential as Ischemic Heart Disease Therapeutics. Front Physiol, 9, 1159. https://doi.org/10.3389/fphys.2018.01159

  28. Peinado, H., Alecˇković, M., Lavotshkin, S., Matei, I., Costa-Silva, B., Moreno-Bueno, G., Hergueta-Redondo, M., Williams, C., García-Santos, G., Ghajar, C. M., Nitadori-Hoshino, A., Hoffman, C., Badal, K., Garcia, B. A., Callahan, M. K., Yuan, J., Martins, V. R., Skog, J., Kaplan, R. N., … Lyden, D. (2012). Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med, 18, 883–891. https://doi.org/10.1038/nm.2753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang, Y., Xiao, X., Zhang, J., Choudhury, R., Robertson, A., Li, K., Ma, M., Burge, C. B., & Wang, Z. (2013). A complex network of factors with overlapping affinities represses splicing through intronic elements. Nature Structural & Molecular Biology., 20, 36–45. https://doi.org/10.1038/nsmb.2459

    Article  CAS  Google Scholar 

  30. Wei, W. J., Mu, S. R., Heiner, M., Fu, X., Cao, L. J., Gong, X. F., Bindereif, A., & Hui, J. (2012). YB-1 binds to CAUC motifs and stimulates exon inclusion by enhancing the recruitment of U2AF to weak polypyrimidine tracts. Nucleic Acids Research., 40, 8622–8636. https://doi.org/10.1093/nar/gks579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lyabin, D. N., Eliseeva, I. A., & Ovchinnikov, L. P. (2014). YB-1 protein: functions and regulation. Wiley Interdisciplinary Reviews., 5, 95–110. https://doi.org/10.1002/wrna.1200

    Article  CAS  PubMed  Google Scholar 

  32. Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G., & Isner, J. M. (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science., 275, 964–967.

    Article  CAS  PubMed  Google Scholar 

  33. Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S. M., Li, B., Pickel, J., McKay, R., Nadal-Ginard, B., Bodine, D. M., Leri, A., & Anversa, P. (2001). Bone marrow cells regenerate infarcted myocardium. Nature., 410, 701–705. https://doi.org/10.1038/35070587

    Article  CAS  PubMed  Google Scholar 

  34. Tomita, S., Li, R. K., Weisel, R. D., Mickle, D. A., Kim, E. J., Sakai, T., & Jia, Z. Q. (1999). Autologous transplantation of bone marrow cells improves damaged heart function. Circulation., 100, II247–II256.

    Article  CAS  PubMed  Google Scholar 

  35. Gnecchi, M., Zhang, Z., Ni, A., & Dzau, V. J. (2008). Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res., 103, 1204–1219. https://doi.org/10.1161/CIRCRESAHA.108.176826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Balsam, L. B., Wagers, A. J., Christensen, J. L., Kofidis, T., Weissman, I. L., & Robbins, R. C. (2004). Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature., 428, 668–673. https://doi.org/10.1038/nature02460

    Article  CAS  PubMed  Google Scholar 

  37. Murry, C. E., Soonpaa, M. H., Reinecke, H., Nakajima, H., Nakajima, H. O., Rubart, M., Pasumarthi, K. B., Virag, J. I., Bartelmez, S. H., Poppa, V., Bradford, G., Dowell, J. D., Williams, D. A., & Field, L. J. (2004). Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature., 428, 664–668. https://doi.org/10.1038/nature02446

    Article  CAS  PubMed  Google Scholar 

  38. Noiseux, N., Gnecchi, M., Lopez-Ilasaca, M., Zhang, L., Solomon, S. D., Deb, A., Dzau, V. J., & Pratt, R. E. (2006). Mesenchymal stem cells overexpressing Akt dramatically repair infarcted myocardium and improve cardiac function despite infrequent cellular fusion or differentiation. Mol Ther., 14, 840–850. https://doi.org/10.1016/j.ymthe.2006.05.016

    Article  CAS  PubMed  Google Scholar 

  39. Hurley, J. H. (2015). ESCRTs are everywhere. The EMBO Journal, 34, 2398–2407. https://doi.org/10.15252/embj.201592484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Roxrud, I., Stenmark, H., & Malerød, L. (2010). ESCRT & Co. Biol. Cell, 102, 293–318. https://doi.org/10.1042/BC20090161

    Article  CAS  PubMed  Google Scholar 

  41. Hurley, J. H., & Hanson, P. I. (2010). Membrane budding and scission by the ESCRT machinery: it's all in the neck. Nat. Rev. Mol. Cell Biol., 11, 556–566. https://doi.org/10.1038/nrm2937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wollert, T., Wunder, C., Lippincott-Schwartz, J., & Hurley, J. H. (2009). Membrane Scission by the ESCRT-III Complex. Nature., 458(7235), 172–177. https://doi.org/10.1038/nature07836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Filimonenko, M., Stuffers, S., Raiborg, C., Yamamoto, A., Malerød, L., Fisher, E. M. C., Isaacs, A., Brech, A., Stenmark, H., & Simonsen, A. (2007). Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. J Cell Biol, 179(3), 485–500. https://doi.org/10.1083/jcb.200702115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Stuffers, S., Wegner, C. S., Stenmark, H., & Brech, A. (2009). Multivesicular endosome biogenesis in the absence of ESCRTS. Traffic, 10, 925–937. https://doi.org/10.1111/j.1600-0854.2009.00920.x

    Article  CAS  PubMed  Google Scholar 

  45. van Niel, G., Charrin, S., Simoes, S., Romao, M., Rochin, L., Saftig, P., Marks, M. S., Rubinstein, E., & Raposo, G. (2011). The tetraspanin CD63 regulates ESCRT-independent and dependent endosomal sorting during melanogenesis. Dev Cell., 21(4), 708–721. https://doi.org/10.1016/j.devcel.2011.08.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bobrie, A., Colombo, M., Raposo, G., & Thery, A. C. (2011). Exosome secretion: molecular mechanisms and rolesin immune responses. Traffic, 12, 1659–1668. https://doi.org/10.1111/j.1600-0854.2011.01225.x

    Article  CAS  PubMed  Google Scholar 

  47. Gnecchi, M., Zhang, Z., Ni, A., & Dzau, V. J. (2008). Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy. Circulation Research., 103, 1204–1219. https://doi.org/10.1161/CIRCRESAHA.108.176826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Maia, J., Caja, S., Strano Moraes, M. C., Couto, N., & Costa-Silva, B. (2018). Exosome-based cell-cell communication in the tumor microenvironment. Front Cell Dev Biol., 6, 18.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Krämer-Albers, E.-M., & Hill, A. F. (2016). Extracellular vesicles: interneural shuttles of complex messages. Curr Opin Neurobiol., 39, 101–107.

    Article  PubMed  Google Scholar 

  50. Crescitelli, R., Lässer, C., Szabó, T. G., Kittel, A., Eldh, M., Dianzani, I., Buzás, E. I., & Lötvall, J. (2013). Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes. J Extracell Vesicles., 2, 20677.

    Article  Google Scholar 

  51. Ludwig, A. K., & Giebel, B. (2012). Exosomes: small vesicles participating in intercellular communication. Int J Biochem Cell Biol., 44, 11–15.

    Article  CAS  PubMed  Google Scholar 

  52. Garcia, N. A., Moncayo-Arlandi, J., Sepulveda, P., & Diez-Juan, A. (2016). Cardiomyocyte exosomes regulate glycolytic flux in endothelium by direct transfer of GLUT transporters and glycolytic enzymes. Cardiovasc Res., 109, 397–408.

    Article  CAS  PubMed  Google Scholar 

  53. Stoorvogel, W. (2015). Resolving sorting mechanisms into exosomes. Cell Research, (25), 531–532. https://doi.org/10.1038/cr.2015.39 published online 31 March 2015.

  54. Colombo, M., Moita, C., van Niel, G., Kowal, J., Vigneron, J., Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. Journal of Cell Science 126, (24). https://doi.org/10.1242/jcs.128868.

  55. van Niel, G., D'Angelo, G., & Raposo, G. (2018). Shedding light on the cell biology of extracellular vesicles. Nature Reviews Molecular Cell Biology, 19, 213–228. https://doi.org/10.1038/nrm.2017.125

    Article  CAS  PubMed  Google Scholar 

  56. Perez-Hernandez, D., Gutiérrez-Vázquez, C., Jorge, I., López-Martín, S., Ursa, A., Sánchez-Madrid, F., Vázquez, J., & Yáñez-Mó, M. (2013). The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. J Biol Chem, 288(17), 11649–11661. https://doi.org/10.1074/jbc.M112.445304 Epub 2013 Mar 5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This research was funded by National institute of Health under RO1 grant (7RO1HL141922-04) to Dr. Sunjay Kaushal.

Author information

Authors and Affiliations

  1. Deininger Lab, Versiti, Blood Research Institute, Milwaukee, WI, USA

    Sameer Ahmad Guru

  2. Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital, 303 E Superior SQRB 4th floor, Chicago, IL, USA

    Sameer Ahmad Guru, Progyaparamita Saha, Ling Chen, Antariksh Tulshyan, Zhi-Dong Ge, Jeanette Baily, Lydia Simons, Artur Stefanowicz, Agata Bilewska, Vivek Mehta, Rachana Mishra, Sudhish Sharma, Swetha Krishnan & Sunjay Kaushal

  3. David Pincus lab, Molecular Genetics and Cell Biology Committee on Cancer Biology, Chicago University, Chicago, IL, USA

    Asif Ali

Authors
  1. Sameer Ahmad Guru
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Progyaparamita Saha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ling Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antariksh Tulshyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhi-Dong Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jeanette Baily
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lydia Simons
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Artur Stefanowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Agata Bilewska
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vivek Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Rachana Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sudhish Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Asif Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Swetha Krishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Sunjay Kaushal
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SAG: Designed and performed experiments, analyzed and interpreted data, wrote manuscript original draft and final manuscript approval. PS: helped in experimentation, data analysis and collection. LC: Performed all animal surgeries. AT: Helped in mouse heart sectioning and staining. ZDG, Supervised and helped trouble shoot, manuscript editing, JB: helped in mouse colony and data maintenance, LS: Helped in heart sectioning and staining, AS: Helped in cell culture and manuscript editing, AB: Cell culture and data maintenance, VM: Manuscript editing and mouse colony maintenance, RM: Helped in data analysis and manuscript review, SS: Supervision in data analysis and manuscript revision, AI: performed the Insilco analysis part for finding of HSEs in the promoter region of YBX1. SK: SK: Supervised the experimental work and edited the manuscript for critical review. The principal investigator of the study.

Corresponding author

Correspondence to Sunjay Kaushal.

Ethics declarations

Competing Interests

The authors declare that they have no conflict of interest.

Ethics approval

The study was ethically approved by ethics committee of Northwestern university and Lurie Children’s hospital, Chicago Ilinois, USA.

Consent to participate

Not applicable.

Consent for publication

All authors listed in the manuscript have given their consent for publication of the research work included in the manuscript.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guru, S.A., Saha, P., Chen, L. et al. HSF-1 enhances cardioprotective potential of stem cells via exosome biogenesis and their miRNA cargo enrichment. Stem Cell Rev and Rep 19, 2038–2051 (2023). https://doi.org/10.1007/s12015-023-10565-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-023-10565-7

Keywords

Search

Navigation