Evidence map›Paper›PMID 33181273›Full record

ArticleNanomedicine : nanotechnology, biology, and medicine2021

Novel nanopolymer RNA therapeutics normalize human diabetic corneal wound healing and epithelial stem cells.

Andrei A Kramerov, Ruchi Shah, Hui Ding, Eggehard Holler, Sue Turjman, Yaron S Rabinowitz, Sean Ghiam, Ezra Maguen, Clive N Svendsen, Mehrnoosh Saghizadeh and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nanomedicine : nanotechnology, biology, and medicine, 2021. 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
1.8field-weighted citation impact, top 12% 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, 22 citations in OpenAlex.

  1. Review
  2. MicroRNA-409-3p/BTG2 signaling axis improves impaired angiogenesis and wound healing in obese mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Corneal Epithelial Regeneration: Old and New Perspectives.International journal of molecular sciences · 2022
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Gene Therapy in the Anterior Eye Segment.Current gene therapy · 2022
    Review
  13. Article
  14. Systemic diseases and the cornea.Experimental eye research · 2021
    Review
  15. 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

12 authors at 2 institutions in 1 country.

Andrei A KramerovEye Program, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Ruchi ShahEye Program, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Hui DingNeurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Eggehard HollerNeurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Sue TurjmanEye Program, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Yaron S RabinowitzEye Program, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Sean GhiamDavid Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Ezra MaguenAmerican Eye Institute, Los Angeles, CA, USA.
Clive N SvendsenBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Mehrnoosh SaghizadehEye Program, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Julia Y LjubimovaBiomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Alexander V LjubimovEye Program, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: ljubimov@cshs.org.
Cedars-Sinai Medical Center · USUniversity of California, Los Angeles · US

Funding

Mechanisms of Epithelial Alterations in Diabetic CorneaR01EY013431 · NEI · CEDARS-SINAI MEDICAL CENTER · PI Alexander V Ljubimov · 2001 to 2026
$11.3M
The Role of MicroRNAs in Normal and Diseased Corneal Epithelial HomeostasisR01EY025377 · NEI · CEDARS-SINAI MEDICAL CENTER · PI Mehrnoosh Saghizadeh Ghiam · 2015 to 2026
$4.3M
Nanoconjugate delivery of proliferation and checkpoint inhibitors to treat glial tumorsR01CA206220 · NCI · CEDARS-SINAI MEDICAL CENTER · PI LJUBIMOVA, JULIA Y · 2016 to 2020
$2.8M
Regulation of Limbal Niche in Normal and Diabetic Cornea by Extracellular VesiclesR01EY029829 · NEI · CEDARS-SINAI MEDICAL CENTER · PI GHIAM, MEHRNOOSH SAGHIZADEH · 2019 to 2023
$2.6M
Wnt5a, a New Diabetic Corneal Marker Related to Wound HealingR01EY031377 · NEI · CEDARS-SINAI MEDICAL CENTER · PI LJUBIMOV, ALEXANDER V · 2020 to 2024
$2.1M
NCI NIH HHS R01 CA206220NEI NIH HHS R01 EY013431NEI NIH HHS R01 EY025377NEI NIH HHS R01 EY029829NEI NIH HHS R01 EY031377
6 · The paper itself

Abstract

Human diabetic corneas develop delayed wound healing, epithelial stem cell dysfunction, recurrent erosions, and keratitis. Adenoviral gene therapy modulating c-Met, cathepsin F and MMP-10 normalized wound healing and epithelial stem cells in organ-cultured diabetic corneas but showed toxicity in stem cell-enriched cultured limbal epithelial cells (LECs). For a safer treatment, we engineered a novel nanobiopolymer (NBC) that carried antisense oligonucleotide (AON) RNA therapeutics suppressing cathepsin F or MMP-10, and miR-409-3p that inhibits c-Met. NBC was internalized by LECs through transferrin receptor (TfR)-mediated endocytosis, inhibited cathepsin F or MMP-10 and upregulated c-Met. Non-toxic NBC modulating c-Met and cathepsin F accelerated wound healing in diabetic LECs and organ-cultured corneas vs. control NBC. NBC treatment normalized levels of stem cell markers (keratins 15 and 17, ABCG2, and ΔNp63), and signaling mediators (p-EGFR, p-Akt and p-p38). Non-toxic nano RNA therapeutics thus present a safe alternative to viral gene therapy for normalizing diabetic corneal cells.

Indexed as

Wound HealingAdenoviridaeAdultAgedAged, 80 and overBiomarkersCells, CulturedCell SurvivalCorneaDiabetes MellitusEpithelial CellsFemaleHumansMaleMiddle AgedNanoparticlesBiomarkersOligonucleotides, AntisensePolymersReceptors, Cell SurfaceRNADiabetic corneaGene therapyLimbal stem cellsmiRNANanobioconjugateRNA therapeuticsWound healing

Identifiers

PMID33181273
PMCPMC8107190
OpenAlexW3099587734

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.