Lysosomal cross-correction by hematopoietic stem cell-derived macrophages via tunneling nanotubes.

Naphade, Swati;Sharma, Jay;Gaide Chevronnay, Héloïse P.;Shook, Michael A;Cherqui, Stephanie;et.al.
(2015) Stem Cells : the international journal of cell differentiation and proliferation — Vol. 33, n° 1, p. 301-309 (2015)

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Authors
  • Naphade, Swati
    Author
  • Sharma, Jay
    Author
  • Gaide Chevronnay, Héloïse P.UCLouvain
    Author
  • Shook, Michael A
    Author
  • Courtoy, PierreUCLouvain
    Author
  • Cherqui, Stephanie
    Author
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Abstract
Despite controversies on the potential of hematopoietic stem cells (HSCs) to promote tissue repair, we previously showed that HSC transplantation could correct cystinosis, a multi-systemic lysosomal storage disease, caused by a defective lysosomal membrane cystine transporter, cystinosin (CTNS). Addressing the cellular mechanisms, we here report vesicular cross-correction after HSC differentiation into macrophages. Upon co-culture with cystinotic fibroblasts, macrophages produced tunneling nanotubes (TNTs) allowing transfer of cystinosin-bearing lysosomes into Ctns-deficient cells, which exploited the same route to retrogradely transfer cystine-loaded lysosomes to macrophages, providing a bidirectional correction mechanism. TNT formation was enhanced by contact with diseased cells. In vivo, HSCs grafted to cystinotic kidneys also generated nanotubular extensions resembling invadopodia that crossed the dense basement membranes and delivered cystinosin into diseased proximal tubular cells. This is the first report of correction of a genetic lysosomal defect by bidirectional vesicular exchange via TNTs and suggests broader potential for HSC transplantation for other disorders due to defective vesicular proteins. Stem Cells 2014.
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Naphade, S., Sharma, J., Gaide Chevronnay, H. P., Shook, M. A., Yeagy, B. A., Rocca, C. J., Ur, S. N., Lau, A. J., Courtoy, P., & Cherqui, S. (2015). Lysosomal cross-correction by hematopoietic stem cell-derived macrophages via tunneling nanotubes. Stem Cells : the international journal of cell differentiation and proliferation, 33(1), 301-309. https://doi.org/10.1002/stem.1835 (Original work published 2015)