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Article

Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells

1
Grupo de Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Ciencias Biomédicas y Medicina, Universdidade da Coruña, 15006 A Coruña, Spain
2
Experimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
*
Authors to whom correspondence should be addressed.
Academic Editor: Sung-Chul Jung
Int. J. Mol. Sci. 2021, 22(7), 3367; https://doi.org/10.3390/ijms22073367
Received: 22 February 2021 / Revised: 21 March 2021 / Accepted: 22 March 2021 / Published: 25 March 2021
Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature. View Full-Text
Keywords: mesenchymal stem cells; inflamm-aging; cellular senescence; SASP; sEV mesenchymal stem cells; inflamm-aging; cellular senescence; SASP; sEV
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MDPI and ACS Style

Mato-Basalo, R.; Morente-López, M.; Arntz, O.J.; van de Loo, F.A.J.; Fafián-Labora, J.; Arufe, M.C. Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells. Int. J. Mol. Sci. 2021, 22, 3367. https://doi.org/10.3390/ijms22073367

AMA Style

Mato-Basalo R, Morente-López M, Arntz OJ, van de Loo FAJ, Fafián-Labora J, Arufe MC. Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells. International Journal of Molecular Sciences. 2021; 22(7):3367. https://doi.org/10.3390/ijms22073367

Chicago/Turabian Style

Mato-Basalo, Rocío, Miriam Morente-López, Onno J. Arntz, Fons A.J. van de Loo, Juan Fafián-Labora, and María C. Arufe 2021. "Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells" International Journal of Molecular Sciences 22, no. 7: 3367. https://doi.org/10.3390/ijms22073367

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