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Platelet?derived growth factor D promotes the angiogenic capacity of endothelial progenitor cells.

ABSTRACT: Neovascularization and re-endothelialization rely on endothelial progenitor cells (EPCs). However, the recruitment and angiogenic roles of EPCs are subject to regulation through the vascular microenvironment, which remains largely unknown. Platelet?derived growth factor D (PDGF?D) is a new member of the PDGF family that binds the PDGFR?? homodimer. However, it remains unknown whether and how it affects the angiogenic capacity of EPCs and participates in tube?like formation. EPCs were derived from rat bone marrow cells, and the gain?of?function approach was used to study the effects of PDGF?D on the biological activities of EPCs. EPCs that stably express PDGF?D were generated by lentiviral?mediated transduction, and the expression levels were evaluated by western blotting and reverse transcription, followed by real?time quantitative polymerase chain reaction (RT?qPCR). The biological activities of EPCs evaluated in the present study included proliferation, adhesion, migration, tube formation and senescence. Furthermore, the downstream signaling of PDGF?D was explored by western blot analysis. The results revealed that the lentiviral?mediated expression of PDGF?D in the microenvironment promoted the migration, proliferation, adhesion and tube formation of EPCs. In addition, PDGF?D suppressed the senescence of EPCs. Mechanistically, PDGF?D induced the phosphorylation of several signaling molecules, including STAT3, AKT, ERK1/2, mTOR and GSK?3?, suggesting that PDGF?D enhanced the angiogenic function of EPCs through PDGF receptor?dependent and ?independent signaling pathways. In conclusion, PDGF?D promotes the angiogenic capacity of EPCs, including proliferation, migration, adhesion and tube formation, and thereby contributes to angiogenesis.

SUBMITTER: Zhang J

PROVIDER: S-EPMC6297765 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Platelet‑derived growth factor D promotes the angiogenic capacity of endothelial progenitor cells.

Zhang Jianbo J Zhang Haolong H Chen Yikuan Y Fu Jian J Lei Yu Y Sun Jianming J Tang Bo B

Molecular medicine reports 20181126 1

Neovascularization and re-endothelialization rely on endothelial progenitor cells (EPCs). However, the recruitment and angiogenic roles of EPCs are subject to regulation through the vascular microenvironment, which remains largely unknown. Platelet‑derived growth factor D (PDGF‑D) is a new member of the PDGF family that binds the PDGFR‑β homodimer. However, it remains unknown whether and how it affects the angiogenic capacity of EPCs and participates in tube‑like formation. EPCs were derived fro ...[more]

PMID: 30483778

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Project description:IntroductionEfficient implementation of peripheral blood-derived endothelial-colony cells (PB-ECFCs) as a therapeutical tool requires isolation and generation of a sufficient number of cells in ex vivo conditions devoid of animal-derived products. At present, little is known how the isolation and expansion procedure in xenogeneic-free conditions affects the therapeutical capacity of PB-ECFCs.ResultsThe findings presented in this study indicate that human platelet lysate (PL) as a serum substitute yields twice more colonies per mL blood compared to the conventional isolation with fetal bovine serum (FBS). Isolated ECFCs displayed a higher proliferative ability in PL supplemented medium than cells in FBS medium during 30 days expansion. The cells at 18 cumulative population doubling levels (CPDL) retained their proliferative capacity, showed higher sprouting ability in fibrin matrices upon stimulation with FGF-2 and VEGF-A than the cells at 6 CPDL, and displayed low ?-galactosidase activity. The increased sprouting of PB-ECFCs at 18 CPDL was accompanied by an intrinsic activation of the uPA/uPAR fibrinolytic system. Induced deficiency of uPA (urokinase-type plasminogen activator) or uPAR (uPA receptor) by siRNA technology completely abolished the angiogenic ability of PB-ECFCs in fibrin matrices. During the serial expansion, the gene induction of the markers associated with inflammatory activation such as VCAM-1 and ICAM-1 did not occur or only to limited extent. While further propagation up to 31 CPDL proceeded at a comparable rate, a marked upregulation of inflammatory markers occurred in all donors accompanied by a further increase of uPA/uPAR gene induction. The observed induction of inflammatory genes at later stages of long-term propagation of PB-ECFCs underpins the necessity to determine the right time-point for harvesting of sufficient number of cells with preserved therapeutical potential.ConclusionThe presented isolation method and subsequent cell expansion in platelet lysate supplemented culture medium permits suitable large-scale propagation of PB-ECFC. For optimal use of PB-ECFCs in clinical settings, our data suggest that 15-20 CPDL is the most adequate maturation stage.

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Platelet?derived growth factor D promotes the angiogenic capacity of endothelial progenitor cells.

Publications

Platelet‑derived growth factor D promotes the angiogenic capacity of endothelial progenitor cells.

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