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Cigarette Smoking Impairs Adipose Stromal Cell Vasculogenic Activity and Abrogates Potency to Ameliorate Ischemia.

ABSTRACT: Cigarette smoking (CS) adversely affects the physiologic function of endothelial progenitor, hematopoietic stem and progenitor cells. However, the effect of CS on the ability of adipose stem/stromal cells (ASC) to promote vasculogenesis and rescue perfusion in the context of ischemia is unknown. To evaluate this, ASC from nonsmokers (nCS-ASC) and smokers (CS-ASC), and their activity to promote perfusion in hindlimb ischemia models, as well as endothelial cell (EC) survival and vascular morphogenesis in vitro were assessed. While nCS-ASC improved perfusion in ischemic limbs, CS-ASC completely lost this therapeutic effect. In vitro vasculogenesis assays revealed that human CS-ASC and ASC from CS-exposed mice showed compromised support of EC morphogenesis into vascular tubes, and the CS-ASC secretome was less potent in supporting EC survival/proliferation. Comparative secretome analysis revealed that CS-ASC produced lower amounts of hepatocyte growth factor (HGF) and stromal cell-derived growth factor 1 (SDF-1). Conversely, CS-ASC secreted the angiostatic/pro-inflammatory factor Activin A, which was not detected in nCS-ASC conditioned media (CM). Furthermore, higher Activin A levels were measured in EC/CS-ASC cocultures than in EC/nCS-ASC cocultures. CS-ASC also responded to inflammatory cytokines with 5.2-fold increase in Activin A secretion, whereas nCS-ASC showed minimal Activin A induction. Supplementation of EC/CS-ASC cocultures with nCS-ASC CM or with recombinant vascular endothelial growth factor, HGF, or SDF-1 did not rescue vasculogenesis, whereas inhibition of Activin A expression or activity improved network formation up to the level found in EC/nCS-ASC cocultures. In conclusion, ASC of CS individuals manifest compromised in vitro vasculogenic activity as well as in vivo therapeutic activity. Stem Cells 2018;36:856-867.

SUBMITTER: Barwinska D

PROVIDER: S-EPMC5992062 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Cigarette Smoking Impairs Adipose Stromal Cell Vasculogenic Activity and Abrogates Potency to Ameliorate Ischemia.

Barwinska Daria D Traktuev Dmitry O DO Merfeld-Clauss Stephanie S Cook Todd G TG Lu Hongyan H Petrache Irina I March Keith L KL

Stem cells (Dayton, Ohio) 20180328 6

Cigarette smoking (CS) adversely affects the physiologic function of endothelial progenitor, hematopoietic stem and progenitor cells. However, the effect of CS on the ability of adipose stem/stromal cells (ASC) to promote vasculogenesis and rescue perfusion in the context of ischemia is unknown. To evaluate this, ASC from nonsmokers (nCS-ASC) and smokers (CS-ASC), and their activity to promote perfusion in hindlimb ischemia models, as well as endothelial cell (EC) survival and vascular morphogen ...[more]

PMID: 29589872

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Project description:INTRODUCTION: Studies have demonstrated that mesenchymal stromal cells (MSCs) could reverse acute and chronic kidney injury by a paracrine or endocrine mechanism, and microvesicles (MVs) have been regarded as a crucial means of intercellular communication. In the current study, we focused on the therapeutic effects of human Wharton-Jelly MSCs derived microvesicles (hWJMSC-MVs) in renal ischemia/reperfusion injury and its potential mechanisms. METHODS: MVs isolated from conditioned medium were injected intravenously in rats immediately after ischemia of the left kidney for 60 minutes. The animals were sacrificed at 24 hours, 48 hours and 2 weeks after reperfusion. The infiltration of inflammatory cells was identified by the immunostaining of CD68+ cells. ELISA was employed to determine the inflammatory factors in the kidney and serum von Willebrand Factor (VWF). Tubular cell proliferation and apoptosis were identified by immunostaining. Renal fibrosis was assessed by Masson's tri-chrome straining and alpha-smooth muscle actin (?-SMA) staining. The CX3CL1 expression in the kidney was measured by immunostaining and Western blot, respectively. In vitro, human umbilical vein endothelial cells were treated with or without MVs for 24 or 48 hours under hypoxia injury to test the CX3CL1 by immunostaining and Western blot. RESULTS: After administration of hWJMSC-MVs in acute kidney injury (AKI) rats, renal cell apoptosis was mitigated and proliferation was enhanced, inflammation was also alleviated in the first 48 hours. MVs also could suppress the expression of CX3CL1 and decrease the number of CD68+ macrophages in the kidney. In the late period, improvement of renal function and abrogation of renal fibrosis were observed. In vitro, MVs could down-regulate the expression of CX3CL1 in human umbilical vein endothelial cells under hypoxia injury at 24 or 48 hours. CONCLUSIONS: A single administration of MVs immediately after ischemic AKI could ameliorate renal injury in both the acute and chronic stage, and the anti-inflammatory property of MVs through suppression of CX3CL1 may be a potential mechanism. This establishes a substantial foundation for future research and treatment.

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Cigarette Smoking Impairs Adipose Stromal Cell Vasculogenic Activity and Abrogates Potency to Ameliorate Ischemia.

Publications

Cigarette Smoking Impairs Adipose Stromal Cell Vasculogenic Activity and Abrogates Potency to Ameliorate Ischemia.

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