Evidence map›Paper›PMID 19829316›Full record

ArticleGene therapy2010

In vivo selection of human embryonic stem cell-derived cells expressing methotrexate-resistant dihydrofolate reductase.

J L Gori, X Tian, D Swanson, R Gunther, L D Shultz, R S McIvor, D S Kaufman

Open access · greenAbstract read
In one paragraph

Article in Gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. A Multidrug-resistant Engineered CAR T Cell for Allogeneic Combination Immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2015
    Article
  3. Article
  4. Article
  5. 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 2 institutions in 2 countries.

J L GoriGene Therapy Program, Department of Genetics, Cell Biology and Development, Institute of Human Genetics, University of Minnesota, Minneapolis, MN 55455, USA.
X Tian
D Swanson
R Gunther
L D Shultz
R S McIvor
D S Kaufman
University of Minnesota · USJackson Laboratory · US

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI William Carl Skarnes · 1985 to 2026
$61.9M
METHOTREXATE--RESISTANCE GENE EXPRESSIONR01CA060803 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MCIVOR, R. SCOTT · 1993 to 2008
$2.4M
Hematopoietic precursor development from human ES cellsR01HL077923 · NHLBI · UNIVERSITY OF MINNESOTA · PI KAUFMAN, DAN S. · 2006 to 2010
$2.1M
NCI NIH HHS CA060803NCI NIH HHS CA34196NCI NIH HHS P30 CA034196NCI NIH HHS R01 CA060803NHLBI NIH HHS HL77923NHLBI NIH HHS R01 HL077923
6 · The paper itself

Abstract

Human embryonic stem cells (hESCs) provide a novel source of hematopoietic and other cell populations suitable for gene therapy applications. Preclinical studies to evaluate engraftment of hESC-derived hematopoietic cells transplanted into immunodeficient mice demonstrate only limited repopulation. Expression of a drug-resistance gene, such as Tyr22-dihydrofolate reductase (Tyr22-DHFR), coupled to methotrexate (MTX) chemotherapy has the potential to selectively increase the engraftment of gene-modified, hESC-derived cells in mouse xenografts. Here, we describe the generation of Tyr22-DHFR-GFP-expressing hESCs that maintain pluripotency, produce teratomas and can differentiate into MTXr-hemato-endothelial cells. We demonstrate that MTX administered to nonobese diabetic/severe combined immunodeficient/IL-2Rgammac(null) (NSG) mice after injection of Tyr22-DHFR-hESC-derived cells significantly increases human CD34(+) and CD45(+) cell engraftment in the bone marrow (BM) and peripheral blood of transplanted MTX-treated mice. These results demonstrate that MTX treatment supports selective, long-term engraftment of Tyr22-DHFR cells in vivo, and provides a novel approach for combined human cell and gene therapy.

Indexed as

AnimalsBone MarrowCell DifferentiationCell LineDrug ResistanceEmbryonic Stem CellsGenetic TherapyGraft SurvivalHumansMethotrexateMiceMice, Inbred NODMice, SCIDStem Cell TransplantationTeratomaTetrahydrofolate DehydrogenaseMethotrexateTetrahydrofolate Dehydrogenase

Identifiers

PMID19829316
PMCPMC2820606
OpenAlexW2107010686

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.