Evidence map›Paper›PMID 26812160›Full record

ArticleEndocrinology2016

Hematopoietic Stem Cells Transplantation Can Normalize Thyroid Function in a Cystinosis Mouse Model.

H P Gaide Chevronnay, V Janssens, P Van Der Smissen, C J Rocca, X H Liao, S Refetoff, C E Pierreux, S Cherqui, P J Courtoy

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.4field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 43 citations in OpenAlex.

  1. Hematopoietic Stem-Cell Gene Therapy for Cystinosis.The New England journal of medicine · 2026
    Trial
  2. Review
  3. Review
  4. Tunneling Nanotubes: The Cables for Viral Spread and Beyond.Results and problems in cell differentiation · 2024
    Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Potential use of stem cells as a therapy for cystinosis.Pediatric nephrology (Berlin, Germany) · 2019
    Review
  19. A deletion in the Ctns gene causes renal tubular dysfunction and cystine accumulation in LEA/Tohm rats.Mammalian genome : official journal of the International Mammalian Genome Society · 2019
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

H P Gaide ChevronnayCell Biology Unit (H.P.G.C., V.J., P.V.D.S., C.E.P., P.J.C.), de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Pediatrics (C.J.R., S.C.), Division of Genetics, University of California, San Diego, San Diego, California 92161; and Departments of Medicine (X.H.L., S.R.) and Pediatrics and Genetics (S.R.), The University of Chicago, Chicago, Illinois 60637.
V JanssensCell Biology Unit (H.P.G.C., V.J., P.V.D.S., C.E.P., P.J.C.), de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Pediatrics (C.J.R., S.C.), Division of Genetics, University of California, San Diego, San Diego, California 92161; and Departments of Medicine (X.H.L., S.R.) and Pediatrics and Genetics (S.R.), The University of Chicago, Chicago, Illinois 60637.
P Van Der SmissenCell Biology Unit (H.P.G.C., V.J., P.V.D.S., C.E.P., P.J.C.), de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Pediatrics (C.J.R., S.C.), Division of Genetics, University of California, San Diego, San Diego, California 92161; and Departments of Medicine (X.H.L., S.R.) and Pediatrics and Genetics (S.R.), The University of Chicago, Chicago, Illinois 60637.
C J RoccaCell Biology Unit (H.P.G.C., V.J., P.V.D.S., C.E.P., P.J.C.), de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Pediatrics (C.J.R., S.C.), Division of Genetics, University of California, San Diego, San Diego, California 92161; and Departments of Medicine (X.H.L., S.R.) and Pediatrics and Genetics (S.R.), The University of Chicago, Chicago, Illinois 60637.
X H LiaoCell Biology Unit (H.P.G.C., V.J., P.V.D.S., C.E.P., P.J.C.), de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Pediatrics (C.J.R., S.C.), Division of Genetics, University of California, San Diego, San Diego, California 92161; and Departments of Medicine (X.H.L., S.R.) and Pediatrics and Genetics (S.R.), The University of Chicago, Chicago, Illinois 60637.
S RefetoffCell Biology Unit (H.P.G.C., V.J., P.V.D.S., C.E.P., P.J.C.), de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Pediatrics (C.J.R., S.C.), Division of Genetics, University of California, San Diego, San Diego, California 92161; and Departments of Medicine (X.H.L., S.R.) and Pediatrics and Genetics (S.R.), The University of Chicago, Chicago, Illinois 60637.
C E PierreuxCell Biology Unit (H.P.G.C., V.J., P.V.D.S., C.E.P., P.J.C.), de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Pediatrics (C.J.R., S.C.), Division of Genetics, University of California, San Diego, San Diego, California 92161; and Departments of Medicine (X.H.L., S.R.) and Pediatrics and Genetics (S.R.), The University of Chicago, Chicago, Illinois 60637.
S CherquiCell Biology Unit (H.P.G.C., V.J., P.V.D.S., C.E.P., P.J.C.), de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Pediatrics (C.J.R., S.C.), Division of Genetics, University of California, San Diego, San Diego, California 92161; and Departments of Medicine (X.H.L., S.R.) and Pediatrics and Genetics (S.R.), The University of Chicago, Chicago, Illinois 60637.
P J CourtoyCell Biology Unit (H.P.G.C., V.J., P.V.D.S., C.E.P., P.J.C.), de Duve Institute and Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Pediatrics (C.J.R., S.C.), Division of Genetics, University of California, San Diego, San Diego, California 92161; and Departments of Medicine (X.H.L., S.R.) and Pediatrics and Genetics (S.R.), The University of Chicago, Chicago, Illinois 60637.
UCLouvain · BEUniversity of California, San Diego · USUniversity of Chicago · US

Funding

THYROID PHYSIOLOGY STUDIES OF INHERITED DISORDERSR37DK015070 · NIDDK · UNIVERSITY OF CHICAGO · PI REFETOFF, SAMUEL · 1989 to 2015
$5.6M
Lentiviral-transduced hematopoictic stem cell transplantation for cystinosisR01DK090058 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHERQUI, STEPHANIE · 2011 to 2019
$2.7M
Toxicology studies for gene-modified stem cell transplantation for cystinosisR01DK099338 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHERQUI, STEPHANIE · 2013 to 2014
$539k
Hematopoietic stem cell-based therapy for Friedrich AtaxiaR21NS090066 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHERQUI, STEPHANIE · 2014 to 2015
$426k
NIDDK NIH HHS R01 DK090058NIDDK NIH HHS R01-DK090058NIDDK NIH HHS R01 DK099338NIDDK NIH HHS R01-DK099338NIDDK NIH HHS R37 DK015070NIDDK NIH HHS R37-DK15070NINDS NIH HHS R21 NS090066NINDS NIH HHS R21-NS090066
6 · The paper itself

Abstract

Hypothyroidism is the most frequent and earliest endocrine complication in cystinosis, a multisystemic lysosomal storage disease caused by defective transmembrane cystine transporter, cystinosin (CTNS gene). We recently demonstrated in Ctns(-/-) mice that altered thyroglobulin biosynthesis associated with endoplasmic reticulum stress, combined with defective lysosomal processing, caused hypothyroidism. In Ctns(-/-) kidney, hematopoietic stem cell (HSC) transplantation provides long-term functional and structural protection. Tissue repair involves transfer of cystinosin-bearing lysosomes from HSCs differentiated as F4/80 macrophages into deficient kidney tubular cells, via tunneling nanotubes that cross basement laminae. Here we evaluated the benefit of HSC transplantation for cystinotic thyroid and investigated the underlying mechanisms. HSC engraftment in Ctns(-/-) thyroid drastically decreased cystine accumulation, normalized the TSH level, and corrected the structure of a large fraction of thyrocytes. In the thyroid microenvironment, HSCs differentiated into a distinct, mixed macrophage/dendritic cell lineage expressing CD45 and major histocompatibility complex II but low CD11b and F4/80. Grafted HSCs closely apposed to follicles and produced tunneling nanotube-like extensions that crossed follicular basement laminae. HSCs themselves further squeezed into follicles, allowing extensive contact with thyrocytes, but did not transdifferentiate into Nkx2.1-expressing cells. Our observations revealed significant differences of basement lamina porosity between the thyroid and kidney and/or intrinsic macrophage invasive properties once in the thyroid microenvironment. The contrast between extensive thyrocyte protection and low HSC abundance at steady state suggests multiple sequential encounters and/or remanent impact. This is the first report demonstrating the potential of HSC transplantation to correct thyroid disease and supports a major multisystemic benefit of stem cell therapy for cystinosis.

Indexed as

Disease Models, AnimalAmino Acid Transport Systems, NeutralAnimalsCell DifferentiationCystineCystinosisFemaleHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHumansLuminescent ProteinsLysosomesMacrophagesMaleMice, Inbred C57BLMice, KnockoutAmino Acid Transport Systems, NeutralCystinecystinosin protein, mouseLuminescent ProteinsThyrotropin

Identifiers

PMID26812160
PMCPMC4816724
OpenAlexW2258933755

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.