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Human and porcine early kidney precursors as a new source for transplantation

Nature Medicine volume 9, pages 53–60 (2003)Cite this article

Abstract

Kidney transplantation has been one of the major medical advances of the past 30 years. However, tissue availability remains a major obstacle. This can potentially be overcome by the use of undifferentiated or partially developed kidney precursor cells derived from early embryos and fetal tissue. Here, transplantation in mice reveals the earliest gestational time point at which kidney precursor cells, of both human and pig origin, differentiate into functional nephrons and not into other, non-renal professional cell types. Moreover, successful organogenesis is achieved when using the early kidney precursors, but not later-gestation kidneys. The formed, miniature kidneys are functional as evidenced by the dilute urine they produce. In addition, decreased immunogenicity of the transplants of early human and pig kidney precursors compared with adult kidney transplants is demonstrated in vivo. Our data pinpoint a window of human and pig kidney organogenesis that may be optimal for transplantation in humans.

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Figure 1: Growth and differentiation of early human and pig kidney precursors after transplantation.
Figure 2: Vascularization of developing kidney transplants by recipient vessels.
Figure 3: Transplants of early embryonic human and pig kidney precursors produce urine.
Figure 4: Differential effect of human PBMC on developing kidney transplants.
Figure 5: Global gene expression patterns of immune-related genes in normal adult and fetal kidneys.

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Acknowledgements

Supported in part by a grant from Mrs. E. Drake and the Gabriella Rich Center for Transplantation Biology Research and the Edward H. Kass Award from the American Physicians Fellowship (B.D.). Y.R. holds the Henry H. Drake Professorial Chair in Immunology.

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Authors and Affiliations

  1. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

    Benjamin Dekel, Tatyana Burakova, Fabian D. Arditti, Shlomit Reich-Zeliger, Oren Milstein & Yair Reisner

  2. Department of Pediatrics, Sheba Medical Center, Tel Hashomer, Israel

    Justen H. Passwell

  3. Functional Genomics Unit, Molecular Hemato-oncology and Respiratory Medicine, Sheba Medical Center, Tel Hashomer, Israel

    Sarit Aviel-Ronen, Gideon Rechavi & Naftali Kaminski

  4. Department of Pediatric Hemato-Oncology, Sheba Medical Center, Tel Hashomer, Israel

    Gideon Rechavi

  5. School of Computer Science and Engineering, Hebrew University, Jerusalem, Israel

    Nir Friedman

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  1. Benjamin Dekel
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Correspondence to Yair Reisner.

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Competing interests

Y.R. is a member of the Scientific Advisory Board and a shareholder of XTL Biopharmaceuticals, Ltd., Ness Ziona, Israel, which has an exclusive license from the Weizmann Institute of Science for the “Trimera” (human/mouse chimera) technology. However, this study was not funded by the company.

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Dekel, B., Burakova, T., Arditti, F. et al. Human and porcine early kidney precursors as a new source for transplantation. Nat Med 9, 53–60 (2003). https://doi.org/10.1038/nm812

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