Evidence map›Paper›PMID 27610394›Full record

ArticleMolecular therapy. Methods & clinical development2016

Preclinical evaluation of mesenchymal stem cells overexpressing VEGF to treat critical limb ischemia.

Julie R Beegle, Nataly Lessa Magner, Stefanos Kalomoiris, Aja Harding, Ping Zhou, Catherine Nacey, Jeannine Logan White, Karen Pepper, William Gruenloh, Geralyn Annett and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

44 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Dual ROS modulation by MnOTheranostics · 2026
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  18. State of the field: cellular and exosomal therapeutic approaches in vascular regeneration.American journal of physiology. Heart and circulatory physiology · 2022
    Review
  19. Review
  20. 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

12 authors.

Julie R BeegleInstitute for Regenerative Cures, University of California Davis , Sacramento, California, USA.
Nataly Lessa MagnerInstitute for Regenerative Cures, University of California Davis , Sacramento, California, USA.
Stefanos KalomoirisInstitute for Regenerative Cures, University of California Davis , Sacramento, California, USA.
Aja HardingInstitute for Regenerative Cures, University of California Davis , Sacramento, California, USA.
Ping ZhouInstitute for Regenerative Cures, University of California Davis , Sacramento, California, USA.
Catherine NaceyInstitute for Regenerative Cures, University of California Davis , Sacramento, California, USA.
Jeannine Logan WhiteInstitute for Regenerative Cures, University of California Davis , Sacramento, California, USA.
Karen PepperInstitute for Regenerative Cures, University of California Davis , Sacramento, California, USA.
William GruenlohInstitute for Regenerative Cures, University of California Davis , Sacramento, California, USA.
Geralyn AnnettInstitute for Regenerative Cures, University of California Davis , Sacramento, California, USA.
Jan A NoltaInstitute for Regenerative Cures, University of California Davis, Sacramento, California, USA; Department of Cell Biology and Human Anatomy, University of California Davis, Sacramento, California, USA.
Fernando A FierroInstitute for Regenerative Cures, University of California Davis, Sacramento, California, USA; Department of Cell Biology and Human Anatomy, University of California Davis, Sacramento, California, USA.

Funding

Direct cell to cell transfer of microRNA for tissue repairR01GM099688 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI NOLTA, JAN A. · 2011 to 2015
$2.7M
Functional dissection of human A-MSC vs BM-MSC phenotypeR01HL073256 · NHLBI · WASHINGTON UNIVERSITY · PI NOLTA, JAN A. · 2003 to 2010
$2.3M
Shared LSRII Cytometer Equipment Application - UC Davis Stem Cell ProgramS10RR026825 · NCRR · UNIVERSITY OF CALIFORNIA AT DAVIS · PI NOLTA, JAN A. · 2010 to 2010
$500k
6 · The paper itself

Abstract

Numerous clinical trials are utilizing mesenchymal stem cells (MSC) to treat critical limb ischemia, primarily for their ability to secrete signals that promote revascularization. These cells have demonstrated clinical safety, but their efficacy has been limited, possibly because these paracrine signals are secreted at subtherapeutic levels. In these studies the combination of cell and gene therapy was evaluated by engineering MSC with a lentivirus to overexpress vascular endothelial growth factor (VEGF). To achieve clinical compliance, the number of viral insertions was limited to 1-2 copies/cell and a constitutive promoter with demonstrated clinical safety was used. MSC/VEGF showed statistically significant increases in blood flow restoration as compared with sham controls, and more consistent improvements as compared with nontransduced MSC. Safety of MSC/VEGF was assessed in terms of genomic stability, rule-out tumorigenicity, and absence of edema or hemangiomas in vivo. In terms of retention, injected MSC/VEGF showed a steady decline over time, with a very small fraction of MSC/VEGF remaining for up to 4.5 months. Additional safety studies completed include absence of replication competent lentivirus, sterility tests, and absence of VSV-G viral envelope coding plasmid. These preclinical studies are directed toward a planned phase 1 clinical trial to treat critical limb ischemia.

Identifiers

PMID27610394
PMCPMC5003097

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.