Evidence map›Paper›PMID 34204193›Full record

ArticleJournal of personalized medicine2021

Efficient Genetic Safety Switches for Future Application of iPSC-Derived Cell Transplants.

Julia Dahlke, Juliane W Schott, Philippe Vollmer Barbosa, Denise Klatt, Anton Selich, Nico Lachmann, Michael Morgan, Thomas Moritz, Axel Schambach

Open access · goldAbstract read
In one paragraph

Article in Journal of personalized medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Stem Cell Therapy: From Idea to Clinical Practice.International journal of molecular sciences · 2022
    Review
  8. Tumorigenicity risk of iPSCsPrecision clinical medicine · 2022
    Review
  9. Frontiers in immunology · 2022
    Review
  10. Strategies to Improve the Safety of iPSC-Derived β Cells for β Cell Replacement in Diabetes.Transplant international : official journal of the European Society for Organ Transplantation · 2022
    Review
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 2 institutions in 2 countries.

Julia DahlkeInstitute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
Juliane W SchottInstitute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
Philippe Vollmer BarbosaInstitute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.ORCID 0000-0001-7693-4422
Denise KlattInstitute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
Anton SelichInstitute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
Nico LachmannInstitute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.ORCID 0000-0002-4245-1497
Michael MorganInstitute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
Thomas MoritzInstitute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
Axel SchambachInstitute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
Medizinische Hochschule Hannover · DEBoston Children's Hospital · US

Funding

Bundesministerium für Bildung und Forschung 01EK1602A, 01EK1602BDeutsche Forschungsgemeinschaft SFB738, REBIRTHNiedersächsisches Ministerium für Wissenschaft und Kultur REBIRTH Center for Translational Regenerative Medicine
6 · The paper itself

Abstract

Induced pluripotent stem cell (iPSC)-derived cell products hold great promise as a potential cell source in personalized medicine. As concerns about the potential risk of graft-related severe adverse events, such as tumor formation from residual pluripotent cells, currently restrict their applicability, we established an optimized tool for therapeutic intervention that allows drug-controlled, specific and selective ablation of either iPSCs or the whole graft through genetic safety switches. To identify the best working system, different tools for genetic iPSC modification, promoters to express safety switches and different safety switches were combined. Suicide effects were slightly stronger when the suicide gene was delivered through lentiviral (LV) vectors compared to integration into the AAVS1 locus through TALEN technology. An optimized HSV-thymidine kinase and the inducible Caspase 9 both mediated drug-induced, efficient in vitro elimination of transgene-positive iPSCs. Choice of promoter allowed selective elimination of distinct populations within the graft: the hOct4 short response element restricted transgene expression to iPSCs, while the CAGs promoter ubiquitously drove expression in iPSCs and their progeny. Remarkably, both safety switches were able to prevent in vivo teratoma development and even effectively eliminated established teratomas formed by LV CAGs-transgenic iPSCs. These optimized tools to increase safety provide an important step towards clinical application of iPSC-derived transplants.

Indexed as

gene editingiC9iPSClentiviral vectorsafe harborsafety switchTK.007

Identifiers

PMID34204193
PMCPMC8234706
OpenAlexW3172334931

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.