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Potentiating Renal Regeneration Using Mesenchymal Stem Cells

Brasile, Lauren, PhD1; Henry, Nicholas1; Orlando, Giuseppe, MD, PhD2; Stubenitsky, Bart, MD, PhD3

doi: 10.1097/TP.0000000000002455
Original Basic Science—General
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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 circulatory death donors were studied. One human kidney was EMS perfused for 24 hours (control), whereas 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. Mesenchymal stem cell treatment led to a significant increase in the synthesis of adenosine triphosphate 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 with 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 adenosine triphosphate, 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.

Perfusion of human kidneys from circulatory death donors with mesenchymal stem cells (MSCs) for 24 hours show increased synthesis of ATP, a reduced inflammatory response, increased synthesis of growth factors and normalization of the cytoskeleton and mitosis versus perfusion without MSCs.

1 Department of Research, BREONICS Inc., Watervliet NY.

2 Department of Surgery, Wake Forest Hospital, Winston-Salem, NC.

3 Department of Plastic Surgery, St. Antonius Hospital, Nieuwegein, Netherlands.

Received 24 May 2018. Revision received 6 September 2018.

Accepted 10 September 2018.

The authors declare no conflicts of interest.

This work was funded by the National Institute of Health R43 grant R43AI106362-01.

L.B. participated in research design, writing of the article, performance of the research, contributed new reagents or analytic tools, and participated in data analysis. N.H. participated in the research design, performance of the research, and data analysis. G.O. participated in the writing of the article. B.S. participated in research design, writing of the article, and data analysis.

Correspondence: Lauren Brasile, PhD, BREONICS INC, 44 Dalliba Ave, Watervliet, NY, 12189. (lbrasile@citlink.net).

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