Characteristics and Function of Cryopreserved Bone Marrow–Derived Endothelial Progenitor Cells

Endothelial progenitor cells (EPC) transplantation has been shown to enhance neovascularization and improve myocardial infarction (MI)-induced ventricular dysfunctions. However, persistent inflammation in the ischemic myocardium, adversely affect EPC survival and function, thereby compromising full benefits of EPC-mediated vascular repair. We hypothesized that modulation of IL-10 signaling in EPCs enhances their mobilization, survival and function in ischemic myocardium after MI. GFP-labeled EPC were transplanted intramyocardially after induction of MI, and the mice were treated with either saline or recombinant IL-10. EPC survival and EPC-mediated neovascularization and myocardial repair were evaluated. IL-10-treated mice showed increased number of GFP+EPCs retention that was associated with reduced EPC apoptosis in the myocardium (P<0.05). The engraftment of EPC into the vascular structures and the associated capillaries density was significantly higher in IL-10-treated mice (P<0.05). The above findings were corroborated with reduced infarct size, fibrosis and enhanced LV function (echocardiography) in IL-10+EPC group as compared to EPC+saline group. Invitro, IL-10-deficient EPCs showed higher LPS-induced apoptosis compared to WT-EPCs (P<0.05). IL-10 treatment induced VEGF expression in WT-EPCs which was abrogated by STAT3 inhibition (using curcurbitacin I). Furthermore, microRNA (miR) profile experiments identified significant increases in a number of pro-apoptotic and anti-angiogenic-related miRs in EPCs from IL-10 deficient mice. Interestingly, IL-10-deficient mice showed impaired MI-induced mobilization of bone marrow EPCs (Sca1+Flk1+ cells) into the circulation and the associated SDF-1 mRNA expression in the myocardium. Bone marrow transplantation studies involving replacement of IL-10-deficient marrow with WT marrow attenuated these effects. Invitro, LPS-induced CXCR4 expression was lower in IL-10-deficient EPCs as compared to WT-EPC. Taken together, our studies suggest that IL-10 enhances EPC mobilization, possibly in an SDF1-CXCR4 dependent manner and increased their survival and neovascularization and the associated myocardial repair, in part via activation of STAT3 signaling cascades.

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Abstract: P253 EFFECTS OF SOPHORCARPIDINE ON NUMBER AND FUNCTION OF ENDOTHELIAL PROGENITOR CELLS FROM BONE MARROW OF SD RAT

Atherosclerosis Supplements ◽

10.1016/s1567-5688(09)70548-3 ◽

2009 ◽

Vol 10 (2) ◽

pp. e560

Author(s):

G Wang ◽

L Xiao ◽

X Wu ◽

C Tang ◽

D Jia ◽

...

Keyword(s):

Bone Marrow ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Endothelial Progenitor ◽

Sd Rat ◽

And Function

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Regulatory effect of dimethylarginine dimethylaminohydrolase on endothelial progenitor cells differentiation and function

Cell Biology International ◽

10.1042/cbi034s042b ◽

2010 ◽

Vol 34 (8) ◽

pp. S42-S42

Author(s):

Qiong Yuan ◽

Chang‑Ping Hu ◽

Si‑Yu Liu ◽

Xu‑Meng Chen ◽

Jun Peng ◽

...

Keyword(s):

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Regulatory Effect ◽

Dimethylarginine Dimethylaminohydrolase ◽

Endothelial Progenitor ◽

And Function

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Quantitative and functional evaluation of endothelial progenitor cells in patients with cardiac amyloidosis

European Heart Journal ◽

10.1093/ehjci/ehaa946.2114 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

O Itzhaki Ben Zadok ◽

D Leshem-Lev ◽

T Ben-Gal ◽

A Hamdan ◽

N Schamroth-Pravda ◽

...

Keyword(s):

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Mtt Assay ◽

Cardiac Amyloidosis ◽

Microvascular Dysfunction ◽

Functional Evaluation ◽

Endothelial Progenitor ◽

Colony Forming Units ◽

Study Population ◽

And Function

Abstract Background Endothelial microvascular dysfunction is a known mechanism of injury in cardiac amyloidosis (CA), but evidence regarding the level and function of endothelial progenitor cells (EPCs) in patients with CA is lacking. Methods Study population included patients with light-chain or transthyretin (ATTR) CA. Patients with diagnosed heart failure and preserved ejection fraction (HFpEF) without monoclonal gammopathy and a 99mTc-DPD scan incompatible with TTR were used as controls. Blood circulating EPCs were assessed quantitatively by the expression of VEGFR-2(+), CD34(+) and CD133(+) using flow cytometry, and functionally by the formation of colony forming units (CFUs). MTT assay was used to demonstrate cell viability. Tests were repeated 3 months following the initiation of amyloid-suppressive therapies (either ATTR-stabilizer or targeted chemotherapy) in CA patients. Results Our preliminary cohort included 14 CA patients (median age 74 years, 62% ATTR CA). Patients with CA vs. patients with HFpEF (n=8) demonstrated lower expression of CD34(+)/VEGFR-2(+) cells [0.51% (IQR 0.4, 0.7) vs. 1.03% (IQR 0.6, 1.4), P=0.043] and CD133(+)/VEGFR-2(+) cells [0.35% (IQR 0.23, 0.52) to 1.07% (IQR 0.6, 1.5), P=0.003]. Functionally, no differences were noted between groups. Following the initiation of amyloid-suppressive therapies in CA patients, we observed the up-regulation of CD34(+)/VEGFR-2(+) cells [2.47% (IQR 2.1, 2.7), P<0.001] and CD133(+)/VEGFR-2(+) cells [1.38% (IQR 1.1, 1.7), P=0.003]. Moreover, functionally, active EPCs were evident microscopically by their ability to form colonies (from 0.5 CFUs [IQR 0, 1.5) to 2 CFUs (IQR 1, 3.5), P=0.023]. EPCs' viability was demonstrated by an MTT assay [0.12 (IQR 0.04, 0.12) to 0.24 (IQR 0.16, 0.3), p=0.014]. Conclusions These preliminary results demonstrate reduced EPCs levels in CA patients indicating significant microvascular impairment. Amyloid-targeted therapies induce the activation of EPCs, thus possibly promoting endothelial regeneration. These findings may represent a novel mechanism of action of amyloid-suppressive therapies EPCs in CA patients and during therapy Funding Acknowledgement Type of funding source: None

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