Evidence map›Paper›PMID 31326745›Full record

ArticleStem cell research2019

Enhanced chondrogenesis from human embryonic stem cells.

Tao Wang, Puwapong Nimkingratana, Christopher A Smith, Aixin Cheng, Timothy E Hardingham, Susan J Kimber

Open access · goldAbstract read
In one paragraph

Article in Stem cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.

  1. Material-Assisted Strategies for Osteochondral Defect Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Pooled it
  2. Article
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  15. Cartilage organoids and osteoarthritis research: a narrative review.Frontiers in bioengineering and biotechnology · 2023
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. SIRT1 activity orchestrates ECM expression during hESC-chondrogenic differentiation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    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

6 authors at 2 institutions in 1 country.

Tao WangFaculty of Biology, Medicine and Health, University of Manchester, UK.
Puwapong NimkingratanaFaculty of Biology, Medicine and Health, University of Manchester, UK.
Christopher A SmithFaculty of Biology, Medicine and Health, University of Manchester, UK.
Aixin ChengFaculty of Biology, Medicine and Health, University of Manchester, UK.
Timothy E HardinghamWellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
Susan J KimberFaculty of Biology, Medicine and Health, University of Manchester, UK. Electronic address: sue.kimber@manchester.ac.uk.
University of Manchester · GBWellcome Centre for Cell-Matrix Research · GB

Funding

Arthritis Research UK 20786Arthritis Research UK R110927Biotechnology and Biological Sciences Research Council BB/D014530/1Medical Research Council G0801057Medical Research Council MC_PC_12018Medical Research Council MR/K026666Medical Research Council MR/K026666/1Medical Research Council MR/K026739/1Medical Research Council MR/L004992/1Medical Research Council MR/L011840/1Medical Research Council MR/M017354/1Medical Research Council MR/S002553/1Versus Arthritis 20786Wellcome Trust
6 · The paper itself

Abstract

Human embryonic stem cells (hESCs) have great potential for the repair of damaged articular cartilage. We developed a serum-free 14-day protocol for hESC differentiation into chondrocyte progenitors, which surprisingly lacked strong cartilage matrix production in in vitro tests. In order to direct these progenitors to a more mature phenotype, we investigated substituting different members of the TGFβ family in the protocol. Initially, we supplemented, or substituted GDF5 (day 11-14), with combinations of BMP7 and TGFβ-1, or -3, but these modifications yielded no improvement in matrix gene expression. However, replacing BMP4 with BMP2 (days 3-10 of the protocol) resulted in a more rapid increase in SOX9 gene expression and increased expression of chondrogenic genes SOX5, ACAN and COL2A1. The replacement of BMP4 with BMP2 also enhanced the formation of chondrogenic cell aggregates, with greater deposition of type II collagen. This change was not accompanied by hypertrophic chondrocyte marker COL10A1 expression. The results demonstrate that BMP2 has greater specificity for the generation of chondrogenic cells from hESCs than BMP4 and this was consistent in two hESC lines (HUES1 and MAN7). hESC-chondrogenic cells derived with either BMP2 or BMP4 were tested in vivo by implanting them in fibrin into osteochondral defects in the femur of RNU rats. Repaired cartilage tissue, positive for Safranin O and type II collagen was detected at 6 and 12 weeks with both cell sources, but the BMP2 cells scored higher for tissue quality (Pineda score). Therefore, BMP2 is more effective at driving chondrogenic differentiation from human pluripotent stem cells than BMP4 and the effect on the resulting chondroprogenitors is sustained in an in vivo setting.

Indexed as

ApoptosisBlotting, WesternBone Morphogenetic Protein 2Bone Morphogenetic Protein 4Cell DifferentiationCell LineChondrogenesisFlow CytometryFluorescent Antibody TechniqueHuman Embryonic Stem CellsHumansBone Morphogenetic Protein 2Bone Morphogenetic Protein 4

Identifiers

PMID31326745
PMCPMC6745516
OpenAlexW2957486497

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.