Search

Stromal-Derived Factor 1&alpha, (SDF) is an angiogenic, chemotactic protein with significant potential for applications in a range of clinical areas, including wound healing, myocardial infarction and orthopaedic regenerative approaches. The 26-min in vivo half-life of SDF, however, has limited its clinical translation to date. In this study, we investigate the use of star-shaped or linear poly(glutamic acid) (PGA) polypeptides to produce PGA&ndash, SDF nanoparticles, which can be incorporated into a tyramine-modified hyaluronic acid hydrogel (HA&ndash, TA) to facilitate sustained localised delivery of SDF. The physicochemical properties and biocompatibility of the PGA&ndash, SDF nanoparticle formulations were extensively characterised prior to incorporation into a HA&ndash, TA hydrogel. The biological activity of the SDF released from the nano-in-gel system was determined on Matrigel&reg, scratch and Transwell&reg, migration assays. Both star-shaped and linear PGA facilitated SDF nanoparticle formation with particle sizes from 255&ndash, 305 nm and almost complete SDF complexation. Star-PGA&ndash, SDF demonstrated superior biocompatibility and was incorporated into a HA&ndash, TA gel, which facilitated sustained SDF release for up to 35 days in vitro. Released SDF significantly improved gap closure on a scratch assay, produced a 2.8-fold increase in HUVEC Transwell&reg, migration and a 1.5-fold increase in total tubule length on a Matrigel&reg, assay at 12 h compared to untreated cells. Overall, we present a novel platform system for the sustained delivery of bioactive SDF from a nano-in-gel system which could be adapted for a range of biomedical applications.

Background The response of progenitor cells (PCs) to transient myocardial ischemia in patients with coronary artery disease remains unknown. We aimed to investigate the PC response to exercise‐induced myocardial ischemia (ExMI) and compare it to flow mismatch during pharmacological stress testing. Methods and Results A total of 356 patients with stable coronary artery disease underwent 99mTc‐sestamibi myocardial perfusion imaging during exercise (69%) or pharmacological stress (31%). CD 34 + and CD 34 + /chemokine (C‐X‐C motif) receptor 4 PC s were enumerated by flow cytometry. Change in PC count was compared between patients with and without myocardial ischemia using linear regression models. Vascular endothelial growth factor and stromal‐derived factor‐1α were quantified. Mean age was 63±9 years; 76% were men. The incidence of Ex MI was 31% and 41% during exercise and pharmacological stress testing, respectively. Patients with Ex MI had a significant decrease in CD 34 + /chemokine (C‐X‐C motif) receptor 4 (−18%, P =0.01) after stress that was inversely correlated with the magnitude of ischemia ( r =−0.19, P =0.003). In contrast, patients without Ex MI had an increase in CD 34 + /chemokine (C‐X‐C motif) receptor 4 (14.7%, P =0.02), and those undergoing pharmacological stress had no change. Plasma vascular endothelial growth factor levels increased (15%, P PC counts in those with Ex MI ( P =0.03), suggesting a greater decrease in PC s in those with a greater change in stromal‐derived factor‐1α level with exercise. Conclusions Ex MI is associated with a significant decrease in circulating levels of CD 34 + /chemokine (C‐X‐C motif) receptor 4 PC s, likely attributable, at least in part, to stromal‐derived factor‐1α–mediated homing of PC s to the ischemic myocardium. The physiologic consequences of this uptake of PC s and their therapeutic implications need further investigation.