Therapeutic Treatment with Sustained-Release Platelet-Rich Plasma Restores Blood Perfusion by Augmenting Ischemia-Induced Angiogenesis and Arteriogenesis in Diabetic Mice

Abstract

Objective: The objective of this investigation was to establish the effectiveness of sustained-release platelet-rich plasma (PRP) on perfusion and neovascularization in diabetic murine hind limb ischemia. Methods: After surgery in streptozotocin-induced diabetic mice, the mice were randomly assigned to the following 4 experimental groups: control (C), 100 µl of the sustained-release form of platelet-poor plasma (PPP), 100 µl of the solution form of PRP (PRP-sol), and 100 µl of the sustained-release form of PRP (PRP-sr). Endpoint evaluations were: blood perfusion by laser Doppler perfusion imaging (LDPI), vascular density by anti-vWF, and mature vessel density by anti-smooth muscle actin antibody. Results: This study demonstrated that a sustained release of PRP increases the perfusion of ischemic tissue as measured by LDPI (57 ± 12; 56 ± 9; 72 ± 7, and 98 ± 4 for the C, PPP, PRP-sol, and PRP-sr groups, respectively; p < 0.05), capillary density (151 ± 16; 158 ± 12; 189 ± 39, and 276 ± 39 for groups C, PPP, PRP-sol, and PRP-sr, respectively; p < 0.05), and mature vessel density (28 ± 2; 31 ± 3; 52 ± 10, and 85 ± 13 for the C, PPP, PRP-sol, and PRP-sr groups, respectively; p < 0.05). Conclusion: A sustained release of PRP containing potent angiogenic growth factors restores blood perfusion by stimulating angiogenesis and arteriogenesis.

Platelet Rich Plasma Clot Releasate Preconditioning Induced PI3K/AKT/NFκB Signaling Enhances Survival and Regenerative Function of Rat Bone Marrow Mesenchymal Stem Cells in Hostile Microenvironments

“…They have also been known to provide beneficial effects on the heart, including neovascularization [46,47] and attenuation of ventricular wall thinning [48]. Previous studies have attributed the angiogenic function of PRP to PDGF and VEGF [49], and the interaction between PDGF and PDGFR is key for the survival of many cells [50]. Specifically, PDGFR is reported to play pivotal roles by transducing extracellular stimuli to intracellular signaling circuits via the PDGF/ PDGFR axis to promote cellular growth and proliferation [51], as well as support pericyte/endothelial cell interplay and vasculature stability [52][53][54].…”

The concept of surgical treatment of critical limb ischemia

“…При-менение стимуляции ангиогенеза представляется оправ-данным способом. На сегодняшний день описаны два ме-тода: терапевтический ангиогенез -введение мононукле-аров костного мозга, обогащенной тромбоцитами плазмы или генных препаратов [5, 13,16,30], и хирургический ангиогенез -за счет трансплантации большого сальника [10].…”

Quantitative Optical Imaging of Vascular Structure and Function in a Model of Peripheral Arterial Disease

“…Recently, these models have been combined in an effort to develop better treatments for DM-PAD patients (64,65). If the diabetes phenotype is characterized with more informative and quantitative techniques such as hyperspectral imaging and OCT, it may lend insights that will ultimately lead to the development of more effective therapeutic treatments for diabetic PAD patients.…”