Potential use of stem cells as a therapy for cystinosis


Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders (LSDs). Initial symptoms of cystinosis correspond to the renal Fanconi syndrome. Patients then develop chronic kidney disease and multi-organ failure due to accumulation of cystine in all tissue compartments. LSDs are commonly characterized by a defective activity of lysosomal enzymes. Hematopoietic stem and progenitor cell (HSPC) transplantation is a treatment option for several LSDs based on the premise that their progeny will integrate in the affected tissues and secrete the functional enzyme, which will be recaptured by the surrounding deficient cells and restore physiological activity. However, in the case of cystinosis, the defective protein is a transmembrane lysosomal protein, cystinosin. Thus, cystinosin cannot be secreted, and yet, we showed that HSPC transplantation can rescue disease phenotype in the mouse model of cystinosis. In this review, we are describing a different mechanism by which HSPC-derived cells provide cystinosin to diseased cells within tissues, and how HSPC transplantation could be an effective one-time treatment to treat cystinosis but also other LSDs associated with a lysosomal transmembrane protein dysfunction.

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We thank Adrien Rocca for the design of the figures.


This work was supported by the National Institute of Health (NIH) RO1-DK090058, the Cystinosis Research Foundation, and the California Institute of Regenerative Medicine (CIRM, CLIN-09230).

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Correspondence to Stephanie Cherqui.

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Competing interests

S.C. is a Scientific Board member and member of the Board of Trustees of the Cystinosis Research Foundation. S.C. is a cofounder, shareholder, and a member of both the scientific board and board of directors of GenStem Therapeutics Inc. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict of interest policies.

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Rocca, C.J., Cherqui, S. Potential use of stem cells as a therapy for cystinosis. Pediatr Nephrol 34, 965–973 (2019). https://doi.org/10.1007/s00467-018-3974-7

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  • Cystinosis
  • Lysosomal storage disorders
  • Hematopoietic stem and progenitor cells
  • Gene therapy
  • Lysosomal transfer
  • Tunneling nanotubes