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 LiCalzi, Chandra Jhadao, Kevin Qian, Sayak K. Mitter, Mohan K. Raizada, Michael E. Boulton, Maria B. Grant

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere93965
JournalPLoS ONE
Volume9
Issue number4
DOIs
StatePublished - Apr 8 2014

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Conditioned Culture Medium
cells
Endothelial cells
endothelial cells
stem cells
hypoxia
Thrombopoietin
stem cell factor
hepatocyte growth factor
Stem Cell Factor
Hepatocyte Growth Factor
bradykinin
Bradykinin
tumor necrosis factors
Medical problems
interleukin-1
Interleukin-1
Arterioles
vascular tissues
Constriction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Vasoreparative dysfunction of CD34+ cells in diabetic individuals involves hypoxic desensitization and impaired autocrine/paracrine mechanisms. / Jarajapu, Yagna P.R.; Hazra, Sugata; Segal, Mark; LiCalzi, Sergio; Jhadao, Chandra; Qian, Kevin; Mitter, Sayak K.; Raizada, Mohan K.; Boulton, Michael E.; Grant, Maria B.

In: PLoS ONE, Vol. 9, No. 4, e93965, 08.04.2014.

Research output: Contribution to journalArticle

Jarajapu, YPR, Hazra, S, Segal, M, LiCalzi, S, Jhadao, C, Qian, K, Mitter, SK, Raizada, MK, Boulton, ME & Grant, MB 2014, 'Vasoreparative dysfunction of CD34+ cells in diabetic individuals involves hypoxic desensitization and impaired autocrine/paracrine mechanisms', PLoS ONE, vol. 9, no. 4, e93965. https://doi.org/10.1371/journal.pone.0093965
Jarajapu, Yagna P.R. ; Hazra, Sugata ; Segal, Mark ; LiCalzi, Sergio ; Jhadao, Chandra ; Qian, Kevin ; Mitter, Sayak K. ; Raizada, Mohan K. ; Boulton, Michael E. ; Grant, Maria B. / Vasoreparative dysfunction of CD34+ cells in diabetic individuals involves hypoxic desensitization and impaired autocrine/paracrine mechanisms. In: PLoS ONE. 2014 ; Vol. 9, No. 4.
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AU - Jhadao, Chandra

AU - Qian, Kevin

AU - Mitter, Sayak K.

AU - Raizada, Mohan K.

AU - Boulton, Michael E.

AU - Grant, Maria B.

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