Evidence map›Paper›PMID 27602403›Full record

ArticleScience advances2016

Small molecule-driven direct conversion of human pluripotent stem cells into functional osteoblasts.

Heemin Kang, Yu-Ru V Shih, Manando Nakasaki, Harsha Kabra, Shyni Varghese

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 3% 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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Revolutionizing bone healing: the role of 3D models.Cell regeneration (London, England) · 2025
    Review
  4. Human-Induced Pluripotent Stem Cells in Plastic and Reconstructive Surgery.International journal of molecular sciences · 2024
    Review
  5. Multi-Functional Small Molecule Alleviates Fracture Pain and Promotes Bone Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Effects ofMaterials (Basel, Switzerland) · 2020
    Article
  18. Article
  19. Review
  20. In Vivo Sequestration of Innate Small Molecules to Promote Bone Healing.Advanced materials (Deerfield Beach, Fla.) · 2020
    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

5 authors at 1 institution in 1 country.

Heemin KangMaterials Science and Engineering Program, University of California, San Diego, La Jolla, CA 92093, USA.
Yu-Ru V ShihDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Manando NakasakiDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Harsha KabraDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Shyni VargheseMaterials Science and Engineering Program, University of California, San Diego, La Jolla, CA 92093, USA.; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
University of California, San Diego · US

Funding

Diversity Supplement -"Bioinspired Synthetic Grafts for Bone Regeneration"R01AR063184 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VARGHESE, SHYNI · 2013 to 2017
$1.7M
NIAMS NIH HHS R01 AR063184
6 · The paper itself

Abstract

The abilities of human pluripotent stem cells (hPSCs) to proliferate without phenotypic alteration and to differentiate into tissue-specific progeny make them a promising cell source for regenerative medicine and development of physiologically relevant in vitro platforms. Despite this potential, efficient conversion of hPSCs into tissue-specific cells still remains a challenge. Herein, we report direct conversion of hPSCs into functional osteoblasts through the use of adenosine, a naturally occurring nucleoside in the human body. The hPSCs treated with adenosine not only expressed the molecular signatures of osteoblasts but also produced calcified bone matrix. Our findings show that the adenosine-mediated osteogenesis of hPSCs involved the adenosine A2bR. When implanted in vivo, using macroporous synthetic matrices, the human induced pluripotent stem cell (hiPSC)-derived donor cells participated in the repair of critical-sized bone defects through the formation of neobone tissue without teratoma formation. The newly formed bone tissues exhibited various attributes of the native tissue, including vascularization and bone resorption. To our knowledge, this is the first demonstration of adenosine-induced differentiation of hPSCs into functional osteoblasts and their subsequent use to regenerate bone tissues in vivo. This approach that uses a physiologically relevant single small molecule to generate hPSC-derived progenitor cells is highly appealing because of its simplicity, cost-effectiveness, scalability, and impact in cell manufacturing, all of which are decisive factors for successful translational applications of hPSCs.

Indexed as

AdenosineCell Culture TechniquesCell DifferentiationHumansInduced Pluripotent Stem CellsOrgan SpecificityOsteoblastsOsteogenesisRegenerative MedicineAdenosineadenosine receptorsadenosine signalingbone repairosteogenic differentiationPluripotent stem cellssmall molecule

Identifiers

PMID27602403
PMCPMC5007071
OpenAlexW2514318958

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.