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Mesenchymal stem cells: a new therapeutic tool for AKI

Nature Reviews Nephrology volume 6, pages 179–183 (2010)Cite this article

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Abstract

Acute kidney injury (AKI) is a common clinical complication, associated with poor outcomes and the development of chronic kidney disease. Despite major advances in the understanding of its pathophysiology, available therapies for AKI are only supportive; therefore, adequate functional recovery from AKI must predominantly rely on the kidney's own reparative ability. An extensive body of preclinical data from our own and from other laboratories has shown that administration of adult multipotent marrow stromal cells (commonly referred to as mesenchymal stem cells [MSCs]), effectively ameliorates experimental AKI by exerting paracrine renoprotective effects and by stimulating tissue repair. Based on these findings, a clinical trial has been conducted to investigate the safety and efficacy of MSCs administered to open-heart surgery patients who are at high risk of postoperative AKI. In this Perspectives article, we discuss some of the early data from this trial and describe potential applications for stem cell therapies in other fields of nephrology.

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Figure 1: Intrarenal actions of MSCs in acute kidney injury.
Figure 2: Mesenchymal stem cells (MSCs) target all pathophysiological components of acute kidney injury (AKI).

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Acknowledgements

The authors' research discussed in this Perspectives article was in part supported by funds from the Merit Review program of the Veterans Administration, Washington, DC, the NIH, the American Heart Association, the National Kidney Foundation, the Western Institute for Biomedical Research, and Allocure, Inc. The human MSCs that were administered to study subjects in the phase I clinical trial were prepared in the cGMP Cell Therapy Facility of the University of Utah, UT, USA. The outstanding skills of the principal investigators (J. Doty, Intermountain Medical Center, Murray, UT; D. Affleck, St. Mark's Hospital, Salt Lake City, UT), co-principal investigators (B. Horne and B. Muhlestein, Intermountain Medical Center; S. Karwande and G. Schorlemmer, St. Mark's Hospital), and study nurses (J. Flores, Intermountain Medical Center; A. Creer, St. Mark's Hospital) are gratefully acknowledged. The contributions of the members of the Data Safety and Monitoring Board for the phase I trial discussed in this article, C. Kablitz, G. R. Reiss, and S. Beddhu, are also greatly appreciated. Finally, the excellent bench work of Z. Hu and P. Zhang for the conduct of the described preclinical studies is acknowledged, and the regulatory contributions of A. Gooch were invaluable for the conduct of the described clinical trial.

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Authors and Affiliations

  1. Department of Medicine, Weill Cornell College of Medicine and New York Presbyterian Hospital, 1300 York Avenue, New York, 10021, NY, USA

    Florian E. Tögel

  2. Division of Nephrology, University of Utah and VA Medical Centers, 500 Foothill Boulevard, Salt Lake City, 84148, UT, USA

    Christof Westenfelder

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  1. Florian E. Tögel
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Correspondence to Christof Westenfelder.

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Competing interests

C. Westenfelder has acted as a consultant, received grant/research support from and is a patent holder/applicant for Allocure. F.E. Tögel declares no competing interests.

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Tögel, F., Westenfelder, C. Mesenchymal stem cells: a new therapeutic tool for AKI. Nat Rev Nephrol 6, 179–183 (2010). https://doi.org/10.1038/nrneph.2009.229

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