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Harnessing the immunological properties of stem cells as a therapeutic option for diabetic nephropathy

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Abstract

Diabetic nephropathy is the leading and possibly the most devastating complication of diabetes, with a prevalence ranging from 25 to 40 % in diabetic individuals, and as such represents an important challenge for public health worldwide. As a major cause of end-stage renal disease, diabetic nephropathy also accounts for a large proportion of deaths in diabetic individuals. To date, therapeutic options for overt diabetic nephropathy include medical interventions to reduce blood glucose levels and to control blood pressure and proteinuria. Recent evidence suggests a strong role for inflammation in the development and progression of diabetic nephropathy. Various immune cells, cytokines and chemokines have been implicated in the onset of diabetic nephropathy, while immune-related transcription factors and adhesion molecules have been correlated with the establishment of a renal proinflammatory microenvironment. Both inflammation and immune activation may promote severe distress in the kidney, with subsequent increased local fibrosis, ultimately leading to the development of end-stage renal disease. Stem cells are undifferentiated cells capable of regenerating virtually any organ or tissue and bearing important immunoregulatory and anti-inflammatory properties. Due to the aforementioned considerations, significant interest has been ignited with regard to the use of stem cells as novel therapeutics for diabetic nephropathy. Here, we will be examining in detail how anti-inflammatory properties of different populations of stem cells may offer novel therapy for the treatment of diabetic nephropathy.

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Acknowledgments

Paolo Fiorina is the recipient of a JDRF Career Development Award, an ASN Career Development Award and an ADA Mentor-based Fellowship grant. P.F. is also supported by a Translational Research Program (TRP) grant from Boston Children’s Hospital, a Harvard Stem Cell Institute grant (“Diabetes Program” DP-0123-12-00) and an Italian Ministry of Health grant (RF-2010-2303119, RF-2010-2314794 and RF-FSR-2008-1213704). Francesca D’Addio is the recipient of an Italian Scientists and Scholars of North America Foundation (ISSNAF)-Fondazione Marche Fellowship.

Conflict of interest

Paolo Fiorina discloses Sorgente S.r.l stock ownership and Otsuka grant funding. Francesca D’Addio, Alessio Trevisani, Moufida Ben Nasr, Roberto Bassi, Basset El Essawy, Reza Abdi, Antonio Secchi declare that they have no conflict of interest.

Statement of human and animal rights

This article does not contain any studies with human subjects performed by the any of the authors. Animal studies were conducted in accordance with institutional and National Institutes of Health guidelines and Institutional Animal Care and Use Committee (IACUC) approval.

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We would like to mention that there are no patients in this study.

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Authors and Affiliations

  1. Transplant Medicine, IRCCS Ospedale San Raffaele, Milan, Italy

    Francesca D’Addio, Roberto Bassi, Antonio Secchi & Paolo Fiorina

  2. Division of Nephrology, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Ave, Enders Building 5th Floor Room En511, Boston, MA, 02115, USA

    Francesca D’Addio, Moufida Ben Nasr, Roberto Bassi & Paolo Fiorina

  3. Università Tor Vergata, Rome, Italy

    Alessio Trevisani

  4. Department of Medicine, Al-Azhar University, Cairo, Egypt

    Basset El Essawy

  5. Nephrology Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Reza Abdi

  6. Universita’ Vita-Salute San Raffaele, Milan, Italy

    Antonio Secchi

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  1. Francesca D’Addio
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  2. Alessio Trevisani
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  3. Moufida Ben Nasr
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  4. Roberto Bassi
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  5. Basset El Essawy
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  6. Reza Abdi
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  7. Antonio Secchi
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  8. Paolo Fiorina
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Correspondence to Paolo Fiorina.

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Managed by Massimo Porta.

Francesca D’Addio and Alessio Trevisani have contributed equally to this work.

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D’Addio, F., Trevisani, A., Ben Nasr, M. et al. Harnessing the immunological properties of stem cells as a therapeutic option for diabetic nephropathy. Acta Diabetol 51, 897–904 (2014). https://doi.org/10.1007/s00592-014-0603-1

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