Brief Reports: Lysosomal Cross‐Correction by Hematopoietic Stem Cell‐Derived Macrophages Via Tunneling Nanotubes

摘要: Despite controversies on the potential of hematopoietic stem cells (HSCs) to promote tissue repair, we previously showed that HSC transplantation could correct cystinosis, a multisystemic lysosomal storage disease, caused by defective membrane cystine transporter, cystinosin (CTNS gene). Addressing cellular mechanisms, here report vesicular cross-correction after differentiation into macrophages. Upon coculture with cystinotic fibroblasts, macrophages produced tunneling nanotubes (TNTs) allowing transfer cystinosin-bearing lysosomes Ctns-deficient cells, which exploited same route retrogradely cystine-loaded macrophages, providing bidirectional correction mechanism. TNT formation was enhanced contact diseased cells. In vivo, HSCs grafted kidneys also generated nanotubular extensions resembling invadopodia crossed dense basement membranes and delivered proximal tubular This is first genetic defect exchange via TNTs suggests broader for other disorders due proteins.