Submitted March 30, 2009
Accepted May 30, 2009
Successful treatment of the murine model of cystinosis using bone marrow cell transplantation
Kimberly Syres, Frank Harrison, Matthew Tadlock, James V. Jester, Jennifer Simpson, Subhojit Roy, Daniel R. Salomon, and Stephanie Cherqui*
The Scripps Research Institute, Department of Molecular and Experimental Medicine, La Jolla, CA, United States
University of California Irvine, Department of Ophthalmology, Orange, CA, United States
University of California San Diego, Department of Neurosciences, La Jolla, CA, United States
* Corresponding author; email: scherqui{at}scripps.edu.
Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders. The defective gene is CTNS encoding the lysosomal cystine transporter, cystinosin. Cystine accumulates in every organ in the body and leads to organ damage and dysfunction including renal defects. Using the murine model for cystinosis, Ctns-/- mice, we performed syngeneic bone marrow cell (BMC), hematopoietic stem cell transplantation (HSC) and mesenchymal stem cell (MSC) transplantation. Organ-specific cystine content was reduced by 57% to 94% in all organs tested in the BMC-treated mice. Confocal microscopy and quantitative-PCR revealed a large quantity of transplanted BMC in all organs tested, from 5% to 19% of the total cells. Most of these cells were not from the lymphoid lineage, but part of the intrinsic structure of the organ. The natural progression of renal dysfunction was prevented and deposition of corneal cystine crystals was significantly improved in the BMC-treated mice. HSC had the same therapeutic effect as whole BMC. In contrast, MSC did not integrate efficiently in any organ. This work is a proof of concept for using HSC transplantation as a therapy for cystinosis and highlights the efficiency of this strategy for a chronic, progressive degenerative disease.
