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Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases.

ABSTRACT: The mechanism for stem cell-mediated improvement following acute myocardial infarction has been actively debated. We support hypotheses that the stem cell effect is primarily paracrine factor-linked. We used a heparin-presenting injectable nanofibre network to bind and deliver paracrine factors derived from hypoxic conditioned stem cell media to mimic this stem cell paracrine effect. Our self-assembling peptide nanofibres presenting heparin were capable of binding paracrine factors from a medium phase. When these factor-loaded materials were injected into the heart following coronary artery ligation in a mouse ischaemia-reperfusion model of acute myocardial infarction, we found significant preservation of haemodynamic function. Through media manipulation, we were able to determine that crucial factors are primarily < 30 kDa and primarily heparin-binding. Using recombinant VEGF- and bFGF-loaded nanofibre networks, the effect observed with conditioned media was recapitulated. When evaluated in another disease model, a chronic rat ischaemic hind limb, our factor-loaded materials contributed to extensive limb revascularization. These experiments demonstrate the potency of the paracrine effect associated with stem cell therapies and the potential of a biomaterial to bind and deliver these factors, pointing to a potential therapy based on synthetic materials and recombinant factors as an acellular therapy.

SUBMITTER: Webber MJ

PROVIDER: S-EPMC3372239 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases.

Webber Matthew J MJ Han Xiaoqiang X Murthy S N Prasanna SN Rajangam Kanya K Stupp Samuel I SI Lomasney Jon W JW

Journal of tissue engineering and regenerative medicine 20101201 8

The mechanism for stem cell-mediated improvement following acute myocardial infarction has been actively debated. We support hypotheses that the stem cell effect is primarily paracrine factor-linked. We used a heparin-presenting injectable nanofibre network to bind and deliver paracrine factors derived from hypoxic conditioned stem cell media to mimic this stem cell paracrine effect. Our self-assembling peptide nanofibres presenting heparin were capable of binding paracrine factors from a medium ...[more]

PMID: 20222010

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Project description:BackgroundA growing number of cohort studies revealed an inverse association between cheese intake and cardiovascular diseases, yet the causal relationship is unclear.ObjectiveTo assess the causal relationship between cheese intake, and cardiovascular diseases and cardiovascular biomarkers.MethodsA two-sample Mendelian randomization (MR) analysis based on publicly available genome-wide association studies was employed to infer the causal relationship. The effect estimates were calculated using the random-effects inverse-variance-weighted method.ResultsCheese intake per standard deviation increase causally reduced the risks of type 2 diabetes (odds ratio (OR) = 0.46; 95% confidence interval (CI), 0.34-0.63; p = 1.02 × 10-6), heart failure (OR = 0.62; 95% CI, 0.49-0.79; p = 0.0001), coronary heart disease (OR = 0.65; 95% CI, 0.53-0.79; p = 2.01 × 10-5), hypertension (OR = 0.67; 95% CI, 0.53-0.84; p = 0.001), and ischemic stroke (OR = 0.76; 95% CI, 0.63-0.91; p = 0.003). Suggestive evidence of an inverse association between cheese intake and peripheral artery disease was also observed. No associations were observed for atrial fibrillation, cardiac death, pulmonary embolism, or transient ischemic attack. The better prognosis associated with cheese intake may be explained by lower body mass index (BMI; effect estimate = -0.58; 95% CI, from -0.88 to -0.27; p = 0.0002), waist circumference (effect estimate = -0.49; 95% CI, from -0.76 to -0.23; p = 0.0003), triglycerides (effect estimate = -0.33; 95% CI, from -0.50 to -0.17; p = 4.91 × 10-5), and fasting glucose (effect estimate = -0.20; 95% CI, from -0.33 to -0.07; p = 0.0003). There was suggestive evidence of a positive association between cheese intake and high-density lipoprotein. No influences were observed for blood pressure or inflammation biomarkers.ConclusionsThis two-sample MR analysis found causally inverse associations between cheese intake and type 2 diabetes, heart failure, coronary heart disease, hypertension, and ischemic stroke.

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Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases.

Publications

Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases.

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