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.

journal_name

J Tissue Eng Regen Med

authors

Webber MJ,Han X,Murthy SN,Rajangam K,Stupp SI,Lomasney JW

doi

10.1002/term.273

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

600-10

issue

8

eissn

1932-6254

issn

1932-7005

journal_volume

4

pub_type

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