Potentiating Renal Regeneration using Mesenchymal Stem Cells

Background The potential of a Mesenchymal Stem Cell (MSC) therapy to accelerate the repair of ischemically damaged human kidneys during 24 hours of warm perfusion was evaluated. The hypothesis was that by administering MSC directly to the renal tissue, there would be an improved opportunity for cellular repair mediated by intrarenal paracrine effects. Methods Studies were performed using the Exsanguinous Metabolic Support (EMS) tissue-engineering platform. Five pairs of human kidney allografts from donation after cardiac death (DCD) donors were studied. One human kidney was EMS perfused for 24 hours (control), while its paired kidney was EMS perfused with MSC (1×108). The kidneys were evaluated for DNA synthesis, cytokine/chemokine synthesis, cytoskeletal regeneration and mitosis. Results Treatment with MSC resulted in reduced inflammatory cytokines synthesized by the kidneys. MSC treatment led to a significant increase in the synthesis of ATP and growth factors resulting in normalization of metabolism and the cytoskeleton. Toluidine Blue staining of MSC treated kidneys demonstrated a significant increase in the number of renal cells undergoing mitosis (26%) compared to EMS perfusion alone. Conclusions To our knowledge, our work is the first to have demonstrated actual renal regeneration while ischemically damaged human kidneys are perfused ex vivo for 24 hours. The observed regeneration entails: increased synthesis of ATP, a reduced inflammatory response, increased synthesis of growth factors, normalization of the cytoskeleton and mitosis. The ability to regenerate renal tissue ex vivo sufficiently to result in immediate function could revolutionize transplantation by solving the chronic organ shortage. Corresponding Author: Lauren Brasile, BREONICS INC, 44 Dalliba Avenue, Watervliet NY, 12189 (lbrasile@citlink.net) Authorship: Lauren Brasile Ph.D. Participated in research design Participated in the writing of the paper Participated in the performance of the research Contributed new reagents or analytic tools Participated in data analysis Nicholas Henry BA. Participated in research design Participated in the performance of the research Participated in data analysis Giuseppe Orlando Ph.D. Participated in the writing of the paper Bart Stubenitsky MD., Ph.D. Participated in research design Participated in the writing of the paper Participated in data analysis Disclosure: The authors declare no conflicts of interest. Funding Sources: This work was funded by the National Institute of Health R43 Grant # R43AI106362-01 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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