Evidence map›Paper›PMID 26880084›Full record

ArticleStem cell research & therapy2016

Attenuation of teratoma formation by p27 overexpression in induced pluripotent stem cells.

Toru Matsu-ura, Hiroshi Sasaki, Motoi Okada, Katsuhiko Mikoshiba, Muhammad Ashraf

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Stem cell and gene therapies for leukodystrophies.Molecular therapy. Methods & clinical development · 2025
    Review
  2. Review
  3. State of the field: cellular and exosomal therapeutic approaches in vascular regeneration.American journal of physiology. Heart and circulatory physiology · 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

5 authors at 3 institutions in 2 countries.

Toru Matsu-uraDepartment of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, 45267-0529, USA. toru.matsuura@uc.edu.
Hiroshi SasakiDepartment of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, 45267-0529, USA. gyn078@poh.osaka-med.ac.jp.
Motoi OkadaDepartment of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, 45267-0529, USA. motoy@asahikawa-med.ac.jp.
Katsuhiko MikoshibaLaboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Saitama, 351-0198, Japan. mikosiba@brain.riken.jp.
Muhammad AshrafDepartment of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, 45267-0529, USA. Ashrafm2@uic.edu.
University of Cincinnati · USRIKEN Center for Brain Science · JPUniversity of Illinois Chicago · US

Funding

Stem Cells in Cardiac Repair and AngiogenesisR37HL074272 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI ASHRAF, MUHAMMAD · 2003 to 2013
$5.7M
Angiomyogenesis With Myoblast Derived iPS CellsR01HL107957 · NHLBI · UNIVERSITY OF CINCINNATI · PI WANG, YIGANG · 2011 to 2015
$3.4M
Integration Free IPS Cells-Derived Progenitors for Cardiac RegenerationR01HL126516 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI REHMAN, JALEES · 2015 to 2019
$3.0M
Wnt11 signaling in stem cell survival and cardiac regenerationR01HL105176 · NHLBI · UNIVERSITY OF CINCINNATI · PI ASHRAF, MUHAMMAD, JONES, WALTER KEITH · 2010 to 2014
$1.9M
NHLBI NIH HHS HL 107957NHLBI NIH HHS HL 126516NHLBI NIH HHS R01 HL105176NHLBI NIH HHS R01 HL107957NHLBI NIH HHS R01 HL126516NHLBI NIH HHS R37 HL074272NHLBI NIH HHS R37-HL074272
6 · The paper itself

Abstract

backgroundPluripotent stem cells, such as embryonic stem cells or induced pluripotent stem cells, have a great potential for regenerative medicine. Induced pluripotent stem cells, in particular, are suitable for replacement of tissue by autologous transplantation. However, tumorigenicity is a major risk in clinical application of both embryonic stem cells and induced pluripotent stem cells. This study explores the possibility of manipulating the cell cycle for inhibition of tumorigenicity.

methodsWe genetically modified mouse induced pluripotent stem cells (miPSCs) to overexpress p27 tumor suppressor and examined their proliferation rate, gene expression, cardiac differentiation, tumorigenicity, and therapeutic potential in a mouse model of coronary artery ligation.

resultsOverexpression of p27 inhibited cell division of miPSCs, and that inhibition was dependent on the expression level of p27. p27 overexpressing miPSCs had pluripotency characteristics but lost stemness earlier than normal miPSCs during embryoid body and teratoma formation. These cellular characteristics led to none or smaller teratoma when the cells were injected into nude mice. Transplantation of both miPSCs and p27 overexpressing miPSCs into the infarcted mouse heart reduced the infarction size and improved left ventricular function.

conclusionsThe overexpression of p27 attenuated tumorigenicity by reducing proliferation and earlier loss of stemness of miPSCs. The overexpression of p27 did not affect pluripotency and differentiation characteristics of miPSC. Therefore, regulation of the proliferation rate of miPSCs offers great therapeutic potential for repair of the injured myocardium.

Indexed as

AnimalsCarcinogenesisCell DifferentiationCell ProliferationCells, CulturedCyclin-Dependent Kinase Inhibitor p27Embryoid BodiesG1 Phase Cell Cycle CheckpointsGene ExpressionInduced Pluripotent Stem CellsMaleMice, Inbred C57BLMice, NudeMyocardial InfarctionMyocardiumStem Cell TransplantationCdkn1b protein, mouseCyclin-Dependent Kinase Inhibitor p27

Identifiers

PMID26880084
PMCPMC4754927
OpenAlexW2274785012

What OpenQuestion holds

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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.