Evidence map›Paper›PMID 24092377›Full record

ArticleTransplantation2014

Rapamycin enhances long-term hematopoietic reconstitution of ex vivo expanded mouse hematopoietic stem cells by inhibiting senescence.

Yi Luo, Lei Li, Ping Zou, Jie Wang, Lijian Shao, Daohong Zhou, Lingbo Liu

Abstract read
In one paragraph

Article in Transplantation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

58 citing papers in PubMed, 70 citations in OpenAlex.

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  17. Autophagy and Metabolism in Normal and Malignant Hematopoiesis.International journal of molecular sciences · 2021
    Review
  18. Review
  19. In search of elixir: Pharmacological agents against stem cell senescence.Iranian journal of basic medical sciences · 2021
    Review
  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

7 authors at 3 institutions in 2 countries.

Yi Luo1 Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2 Division of Radiation Health, Department of Pharmaceutical Sciences and Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR. 3 Institute of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 4 Address correspondence to: Lingbo Liu, M.D., Ph.D., Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China and Daohong Zhou, M.D., Division of Radiation Health, Department of Pharmaceutical Sciences and Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 West Markham, #607, Little Rock, AR 72205.
Lei Li
Ping Zou
Jie Wang
Lijian Shao
Daohong Zhou
Lingbo Liu
Huazhong University of Science and Technology · CNUnion Hospital · CNUniversity of Arkansas for Medical Sciences · US

Funding

Role of p38 MAPK in HSC Self-Renewal and Radiation-Induced Bone Marrow InjuryR01AI080421 · NIAID · UNIV OF ARKANSAS FOR MED SCIS · PI ZHOU, DAOHONG · 2008 to 2012
$1.8M
NIAID NIH HHS AI080421NIAID NIH HHS R01 AI080421
6 · The paper itself

Abstract

backgroundThe mammalian target of rapamycin (mTOR) is an important regulator of hematopoietic stem cell (HSC) self-renewal and its overactivation contributes to HSC premature exhaustion in part via induction of HSC senescence. Inhibition of mTOR with rapamycin has the potential to promote long-term hematopoiesis of ex vivo expanded HSCs to facilitate the clinical application of HSC transplantation for various hematologic diseases.

methodsA well-established ex vivo expansion system for mouse bone marrow HSCs was used to investigate whether inhibition of overactivated mTOR with rapamycin can promote long-term hematopoiesis of ex vivo expanded HSCs and to elucidate the mechanisms of action of rapamycin.

resultsHSC-enriched mouse bone marrow LSK cells exhibited a time-dependent activation of mTOR after ex vivo expansion in a serum-free medium supplemented with stem cell factor, thrombopoietin, and Flt3 ligand. The overactivation of mTOR was associated with induction of senescence but not apoptosis in LSK cells and a significant reduction in the ability of HSCs to produce long-term hematopoietic reconstitution. Inhibition of overactivated mTOR with rapamycin promoted ex vivo expansion and long-term hematopoietic reconstitution of HSCs. The increase in long-term hematopoiesis of expanded HSCs is likely attributable in part to rapamycin-mediated up-regulation of Bmi1 and down-regulation of p16, which prevent HSCs from undergoing senescence during ex vivo expansion.

conclusionsThese findings suggest that mTOR plays an important role in the regulation of HSC self-renewal in vitro and inhibition of mTOR hyperactivation with rapamycin may represent a novel approach to promote ex vivo expansion and their long-term hematopoietic reconstitution of HSCs.

Indexed as

AnimalsCell ProliferationCells, CulturedCellular SenescenceCyclin-Dependent Kinase Inhibitor p16HematopoiesisHematopoietic Stem CellsMiceMice, Inbred C57BLPolycomb Repressive Complex 1Protein Kinase InhibitorsProto-Oncogene ProteinsSignal TransductionSirolimusTime FactorsTOR Serine-Threonine KinasesBmi1 protein, mouseCdkn2a protein, mouseCyclin-Dependent Kinase Inhibitor p16mTOR protein, mousePolycomb Repressive Complex 1Protein Kinase InhibitorsProto-Oncogene ProteinsSirolimusTOR Serine-Threonine Kinases

Identifiers

PMID24092377
PMCPMC3877183
OpenAlexW2079465474

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.