Skip to Content
MilliporeSigma
  • Brief reports: Lysosomal cross-correction by hematopoietic stem cell-derived macrophages via tunneling nanotubes.

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

Stem cells (Dayton, Ohio) (2014-09-05)
Swati Naphade, Jay Sharma, Héloïse P Gaide Chevronnay, Michael A Shook, Brian A Yeagy, Celine J Rocca, Sarah N Ur, Athena J Lau, Pierre J Courtoy, Stephanie Cherqui
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 multisystemic lysosomal storage disease, caused by a defective lysosomal membrane cystine transporter, cystinosin (CTNS gene). Addressing the cellular mechanisms, we here report vesicular cross-correction after HSC differentiation into macrophages. Upon coculture 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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Dehydrated Alcohol, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Sodium hydroxide concentrate, 0.1 M NaOH in water (0.1N), Eluent concentrate for IC
Sigma-Aldrich
Ethanol, 94.8-95.8%
Sigma-Aldrich
Sodium hydroxide solution, 0.1 M
Sigma-Aldrich
Sodium hydroxide solution, 4 M
Sigma-Aldrich
Sodium hydroxide, JIS special grade, ≥96.0%
Sigma-Aldrich
Tannic acid, SAJ first grade
Sigma-Aldrich
Sodium hydroxide solution, 0.01 M
Sigma-Aldrich
Sodium hydroxide solution, 7 M
Sigma-Aldrich
Glutaraldehyde solution, SAJ first grade, 20.0-26.0%
Sigma-Aldrich
Sodium hydroxide solution, 6 M
Sigma-Aldrich
Sodium hydroxide solution, 1 M
Sigma-Aldrich
Ethanol, JIS special grade, 94.8-95.8%
Sigma-Aldrich
Sodium sulfate, JIS special grade, ≥99.0%
Sigma-Aldrich
Glutaraldehyde solution, 50 wt. % in H2O
Sigma-Aldrich
Sodium hydroxide, SAJ first grade, ≥95.0%
Sigma-Aldrich
Sodium hydroxide solution, 0.2 M
Sigma-Aldrich
Sodium sulfate, BioUltra, anhydrous, ≥99.0% (T)
Sigma-Aldrich
Osmium tetroxide, Sealed ampule.
Sigma-Aldrich
Sodium hydroxide solution, 1.0 N, BioReagent, suitable for cell culture
Sigma-Aldrich
Glutaraldehyde solution, Grade I, 50% in H2O, specially purified for use as an electron microscopy fixative or other sophisticated use
Sigma-Aldrich
Glutaraldehyde solution, Grade I, 25% in H2O, specially purified for use as an electron microscopy fixative
Sigma-Aldrich
Glutaraldehyde solution, Grade II, 25% in H2O
Sigma-Aldrich
Glutaraldehyde solution, 50% in H2O, suitable for photographic applications
Sigma-Aldrich
Glutaraldehyde solution, Grade I, 8% in H2O, specially purified for use as an electron microscopy fixative or other sophisticated use
Sigma-Aldrich
Ethanol Fixative 80% v/v, suitable for fixing solution (blood films)
Sigma-Aldrich
Sodium sulfate, ≥99.0%, suitable for plant cell culture
Sigma-Aldrich
Bicinchoninic acid disodium salt hydrate, ≥98% (HPLC)
Sigma-Aldrich
Sodium sulfate, BioXtra, ≥99.0%
Sigma-Aldrich
Glutaraldehyde solution, Grade I, 70% in H2O, specially purified for use as an electron microscopy fixative or other sophisticated use