Evidence map›Paper›PMID 24713821›Full record

ArticlePloS one2014

Vasoreparative dysfunction of CD34+ cells in diabetic individuals involves hypoxic desensitization and impaired autocrine/paracrine mechanisms.

Yagna P R Jarajapu, Sugata Hazra, Mark Segal, Sergio Li Calzi, Sergio LiCalzi, Chandra Jadhao, Chandra Jhadao, Kevin Qian, Sayak K Mitter, Mohan K Raizada and 2 more

Erratum issued Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04255004 (Autologous Peripheral Blood Mononuclear Cells for Limb Salvage in Diabetic Foot Patients With No-option Critical Limb Ischemia), which is not on this map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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.

NCT04255004 nacompletednot on this map

Autologous Peripheral Blood Mononuclear Cells for Limb Salvage in Diabetic Foot Patients With No-option Critical Limb Ischemia

TypeinterventionalSponsorOspedale San DonatoRan2014 to 2019Enrolled76ConditionsCritical Limb Ischemia, Diabetic FootArmsPall Celeris System, point of care device for human cell therapy
3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.

  1. Guideline
  2. Resilient Calvarial Bone Marrow Supports Retinal Repair in Type 2 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Direct in vivo reprogramming to relieve tissue ischemia via induced vasculogenesis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  4. Article
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  6. Review
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  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. CD34 positive cells as endothelial progenitor cells in biology and medicine.Frontiers in cell and developmental biology · 2023
    Review
  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

  • Erratum issued
    LiCalzi, Sergio [corrected to Li Calzi, Sergio]; Jhadao, Chandra [corrected to Jadhao, Chandra]
5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Yagna P R JarajapuDepartment of Pharmaceutical Sciences, College of Pharmacy, Nursing, and Allied Sciences, North Dakota State University, Fargo, North Dakota, United States of America; Departments of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
Sugata HazraDepartments of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
Mark SegalDepartment of Nephrology, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
Sergio Li Calzi
Sergio LiCalziDepartment of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
Chandra Jadhao
Chandra JhadaoDepartments of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
Kevin QianDepartment of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
Sayak K MitterDepartment of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
Mohan K RaizadaDepartment of Physiology and Functional Genomics College of Medicine, University of Florida, Gainesville, Florida, United States of America.
Michael E BoultonDepartment of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
Maria B GrantDepartments of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, United States of America; Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
University of Florida · USIndiana University School of MedicineIndiana University – Purdue University Indianapolis · US

Funding

NITRIC OXIDE IN THE PATHOGENESIS OF DIABETIC RETINOPATHYR01EY012601 · NEI · UNIVERSITY OF FLORIDA · PI Julia V Busik, Maria Bartolomeo Grant · 1998 to 2026
$9.6M
Targeting the IGF-1 System in Retinal AngiogenesisR01EY007739 · NEI · UNIVERSITY OF FLORIDA · PI ABCOUWER, STEVEN F, GRANT, MARIA BARTOLOMEO · 1995 to 2015
$5.4M
UFRCC for Cardiovascular Cell Therapy Research NetworkUM1HL087366 · NHLBI · UNIVERSITY OF FLORIDA · PI PEPINE, CARL J · 2012 to 2018
$4.7M
UFCC for Cardiovascular Cell Therapy Research NetworkU01HL087366 · NHLBI · UNIVERSITY OF FLORIDA · PI PEPINE, CARL J · 2007 to 2011
$2.6M
Targeting gamma-secretase activation for anti-angiogenesisR01EY018358 · NEI · UNIVERSITY OF TEXAS MED BR GALVESTON · PI BOULTON, MICHAEL EDWIN · 2007 to 2012
$2.2M
NO Dysregulation of the Peripheral Clock in Diabetic ComplicationsR01DK090730 · NIDDK · UNIVERSITY OF FLORIDA · PI GRANT, MARIA BARTOLOMEO · 2010 to 2013
$1.3M
HORMONES &NEOVASCULARIZATION IN DIABETIC RETINOPATHYR29EY007739 · NEI · UNIVERSITY OF FLORIDA · PI GRANT, MARIA B · 1989 to 1993
–
NEI NIH HHS EY007739NEI NIH HHS EY012601NEI NIH HHS EY018358NEI NIH HHS R01 EY007739NEI NIH HHS R01 EY012601NEI NIH HHS R01 EY018358NHLBI NIH HHS U01 HL087366NHLBI NIH HHS U01HL087366NHLBI NIH HHS UM1 HL087366NIDDK NIH HHS DK090730-02NIDDK NIH HHS R01 DK090730
6 · The paper itself

Abstract

We hypothesized that endothelial progenitor cells derived from individuals with diabetes would exhibit functional defects including inability to respond to hypoxia and altered paracrine/autocrine function that would impair the angiogenic potential of these cells. Circulating mononuclear cells isolated from diabetic (n = 69) and nondiabetic (n = 46) individuals were used to grow endothelial colony forming cells (ECFC), early endothelial progenitor cells (eEPCs) and isolate CD34+ cells. ECFCs and eEPCs were established from only 15% of the diabetic individuals tested thus directing our main effort toward examination of CD34+ cells. CD34+ cells were plated in basal medium to obtain cell-free conditioned medium (CM). In CM derived from CD34+ cells of diabetic individuals (diabetic-CM), the levels of stem cell factor, hepatocyte growth factor, and thrombopoietin were lower, and IL-1β and tumor necrosis factor (TNFα) levels were higher than CM derived from nondiabetic individuals (nondiabetic-CM). Hypoxia did not upregulate HIF1α in CD34+ cells of diabetic origin. Migration and proliferation of nondiabetic CD34+ cells toward diabetic-CM were lower compared to nondiabetic-CM. Attenuation of pressure-induced constriction, potentiation of bradykinin relaxation, and generation of cGMP and cAMP in arterioles were observed with nondiabetic-CM, but not with diabetic-CM. Diabetic-CM failed to induce endothelial tube formation from vascular tissue. These results suggest that diabetic subjects with microvascular complications exhibit severely limited capacity to generate ex-vivo expanded endothelial progenitor populations and that the vasoreparative dysfunction observed in diabetic CD34+ cells is due to impaired autocrine/paracrine function and reduced sensitivity to hypoxia.

Indexed as

AdultAgedAntigens, CD34Cells, CulturedDiabetes Mellitus, Type 2Endothelial CellsHepatocyte Growth FactorHumansHypoxiaMaleMiddle AgedNeovascularization, PhysiologicStem Cell FactorStem CellsThrombopoietinTumor Necrosis Factor-alphaAntigens, CD34Hepatocyte Growth FactorStem Cell FactorThrombopoietinTumor Necrosis Factor-alpha

Identifiers

PMID24713821
PMCPMC3979711
OpenAlexW1966470795

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Registered trials

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.