Evidence map›Paper›PMID 21689066›Full record

ArticleStem cells and development2012

Three-dimensional spheroid culture of human gingiva-derived mesenchymal stem cells enhances mitigation of chemotherapy-induced oral mucositis.

Qunzhou Zhang, Andrew L Nguyen, Shihong Shi, Colin Hill, Petra Wilder-Smith, Tatiana B Krasieva, Anh D Le

Open access · greenAbstract read
In one paragraph

Article in Stem cells and development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

103 citing papers in PubMed, 193 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Article
  6. Mesenchymal Stem Cell Therapy for Oral Lichen Planus: A Paradigm Shift from Palliation to Regeneration.International journal of hematology-oncology and stem cell research · 2026
    Article
  7. Review
  8. The Therapeutic Scope of Orofacial Mesenchymal Stem Cells.Bioengineering (Basel, Switzerland) · 2025
    Review
  9. Review
  10. Article
  11. Article
  12. Gingival Mesenchymal Stem Cells: A Periodontal Regenerative Substitute.Tissue engineering and regenerative medicine · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review

43 more citing papers are in PubMed but not listed here.

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

7 authors at 3 institutions in 1 country.

Qunzhou ZhangCenter for Craniofacial Molecular Biology, The Herman Ostrow School of Dentistry of University of Southern California, Los Angeles, California 90033, USA.
Andrew L Nguyen
Shihong Shi
Colin Hill
Petra Wilder-Smith
Tatiana B Krasieva
Anh D Le
Beckman Laser Institute and Medical Clinic · USUniversity of California, Irvine · USUniversity of Southern California · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Christine Hui · 1994 to 2026
$57.9M
WOUND MIGRATION FORCE MONITORINGP41RR001192 · NCRR · UNIVERSITY OF CALIFORNIA-IRVINE · PI LYUBOVITSKY, JULIA · 1985 to 2011
$14.2M
GINGIVA DERIVED MSCS: ROLE IN IMMUNOMODULATION AND TISSUE REGENERATIONR01DE019932 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LE, ANH D, SHI, SONGTAO · 2009 to 2013
$2.8M
NCI NIH HHS P30 CA062203NCRR NIH HHS D41-RR01192NIDCR NIH HHS R01 DE019932NIDCR NIH HHS R01DE 019932
6 · The paper itself

Abstract

Mesenchymal stem cells (MSCs) are capable of regenerative and immunomodulatory functions in cell-based therapies in a variety of human diseases and injuries; however, their therapeutic efficacy and potential side effects remain major obstacles in clinical applications. We report here a 3D spheroid culture approach to optimize stem cell properties and therapeutic effects of human gingiva-derived mesenchymal stem cells (GMSCs) in mitigation of experimental oral mucositis. Under growth condition of ultra-low attachment, GMSCs spontaneously aggregated into 3D spheroids and exhibited distinct early stem cell phenotype characterized by elevated expression Stro-1 and CXC chemokine receptor 4 (CXCR-4) as well as OCT-4 and Nanog, 2 important transcriptional factors relevant to stem cell properties, and decreased expression of MSC-associated markers, including CD29, CD90, and CD105. Functionally, spheroid GMSCs are capable of enhanced multipotency and augmented secretion of several chemokines and cytokines relevant to cell migration, survival, and angiogenesis. More importantly, spheroid GMSCs expressed increased levels of reactive oxygen species, hypoxia-inducible factor (HIF)-1 and -2α, and manganese superoxide dismutase, which correlated with improved resistance to oxidative stress-induced apoptosis. Using an in vivo murine model of chemotherapy-induced oral mucositis, we demonstrated that spheroid-derived GMSCs possessed better therapeutic efficacy than their adherent cells in reversing body weight loss and promoting the regeneration of disrupted epithelial lining of the mucositic tongues. These findings suggest that 3D spheroid culture allows early stemness preservation and potentially precondition GMSCs for enhanced mitigation of oral mucositis.

Indexed as

Drug-Related Side Effects and Adverse ReactionsAnimalsCell Culture TechniquesGingivaMesenchymal Stem CellsMesenchymal Stem Cell TransplantationMiceSpheroids, CellularStomatitisTreatment Outcome

Identifiers

PMID21689066
PMCPMC3315752
OpenAlexW1963993157

What OpenQuestion holds

Textmetadata
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.