Evidence map›Paper›PMID 32260086›Full record

ArticleInternational journal of molecular sciences2020

Targeted Integration of Inducible Caspase-9 in Human iPSCs Allows Efficient

Alexandra Lipus, Ewa Janosz, Mania Ackermann, Miriam Hetzel, Julia Dahlke, Theresa Buchegger, Stephanie Wunderlich, Ulrich Martin, Toni Cathomen, Axel Schambach and 2 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

15 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. The concealed side of caspases: beyond a killer of cells.Cellular and molecular life sciences : CMLS · 2024
    Review
  6. Review
  7. Building Blocks of Artificial CRISPR-Based Systems beyond Nucleases.International journal of molecular sciences · 2022
    Review
  8. Article
  9. Review
  10. Article
  11. Article
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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

12 authors at 2 institutions in 1 country.

Alexandra LipusRG Reprogramming and Gene Therapy, Hannover Medical School, Hannover 30625, Germany.
Ewa JanoszRG Reprogramming and Gene Therapy, Hannover Medical School, Hannover 30625, Germany.
Mania AckermannInstitute of Experimental Hematology, REBIRTH, Hannover Medical School, Hannover 30625, Germany.ORCID 0000-0002-0496-200X
Miriam HetzelRG Reprogramming and Gene Therapy, Hannover Medical School, Hannover 30625, Germany.
Julia DahlkeInstitute of Experimental Hematology, REBIRTH, Hannover Medical School, Hannover 30625, Germany.
Theresa BucheggerInstitute of Experimental Hematology, REBIRTH, Hannover Medical School, Hannover 30625, Germany.
Stephanie WunderlichLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, REBIRTH, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, Hannover 30625, Germany.
Ulrich MartinLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, REBIRTH, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, Hannover 30625, Germany.
Toni CathomenInstitute for Transfusion Medicine and Gene Therapy, Medical Center-University of Freiburg, Freiburg 79106, Germany.ORCID 0000-0002-7757-4630
Axel SchambachInstitute of Experimental Hematology, REBIRTH, Hannover Medical School, Hannover 30625, Germany.
Thomas MoritzRG Reprogramming and Gene Therapy, Hannover Medical School, Hannover 30625, Germany.
Nico LachmannInstitute of Experimental Hematology, REBIRTH, Hannover Medical School, Hannover 30625, Germany.ORCID 0000-0002-4245-1497
Medizinische Hochschule Hannover · DEUniversity of Freiburg · DE

Funding

Deutsche Forschungsgemeinschaft Exc 62/2Deutsche Forschungsgemeinschaft iCARE 01EK1601ADeutsche Forschungsgemeinschaft iMACnet 01EK1602ADeutsche Forschungsgemeinschaft LA 3680/2-1Deutsche Zentrum für Lungenforschung 82DZL002A1SFB SFB738
6 · The paper itself

Abstract

Induced pluripotent stem cells (iPSCs) offer great promise for the field of regenerative medicine, and iPSC-derived cells have already been applied in clinical practice. However, potential contamination of effector cells with residual pluripotent cells (e.g., teratoma-initiating cells) or effector cell-associated side effects may limit this approach. This also holds true for iPSC-derived hematopoietic cells. Given the therapeutic benefit of macrophages in different disease entities and the feasibility to derive macrophages from human iPSCs, we established human iPSCs harboring the inducible Caspase-9 (iCasp9) suicide safety switch utilizing transcription activator-like effector nuclease (TALEN)-based designer nuclease technology. Mono- or bi-allelic integration of the iCasp9 gene cassette into the AAVS1 locus showed no effect on the pluripotency of human iPSCs and did not interfere with their differentiation towards macrophages. In both, iCasp9-mono and iCasp9-bi-allelic clones, concentrations of 0.1 nM AP20187 were sufficient to induce apoptosis in more than 98% of iPSCs and their progeny-macrophages. Thus, here we provide evidence that the introduction of the iCasp9 suicide gene into the AAVS1 locus enables the effective clearance of human iPSCs and thereof derived macrophages.

Indexed as

Caspase 9Cell DifferentiationCell LineGenes, Transgenic, SuicideHumansInduced Pluripotent Stem CellsMacrophagesRegenerative MedicineTacrolimusAP20187Caspase 9Tacrolimuscell therapyinducible caspase 9iPSCmacrophagessuicide genes

Identifiers

PMID32260086
PMCPMC7177583
OpenAlexW3015076075

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.