The sustained PGE2 release matrix improves neovascularization and skeletal muscle regeneration in a hindlimb ischemia model

Abstract

Background The promising therapeutic strategy for the treatment of peripheral artery disease (PAD) is to restore blood supply and promote regeneration of skeletal muscle regeneration. Increasing evidence revealed that prostaglandin E2 (PGE2), a lipid signaling molecule, has significant therapeutic potential for tissue repair and regeneration. Though PGE2 has been well reported in tissue regeneration, the application of PGE2 is hampered by its short half-life in vivo and the lack of a viable system for sustained release of PGE2. Results In this study, we designed and synthesized a new PGE2 release matrix by chemically bonding PGE2 to collagen. Our results revealed that the PGE2 matrix effectively extends the half-life of PGE2 in vitro and in vivo. Moreover, the PGE2 matrix markedly improved neovascularization by increasing angiogenesis, as confirmed by bioluminescence imaging (BLI). Furthermore, the PGE2 matrix exhibits superior therapeutic efficacy in the hindlimb ischemia model through the activation of MyoD1-mediated muscle stem cells, which is consistent with accelerated structural recovery of skeletal muscle, as evidenced by histological analysis. Conclusions Our findings highlight the chemical bonding strategy of chemical bonding PGE2 to collagen for sustained release and may facilitate the development of PGE2-based therapies to significantly improve tissue regeneration. Graphical Abstract

Superior protective effects of PGE2 priming mesenchymal stem cells against LPS-induced acute lung injury (ALI) through macrophage immunomodulation

“…Several cell types can produce PGE2, such as fibroblasts and inflammatory cells, and the distinct secretion of PGE2 occurs during the immune response [ 54 , 55 ]. It has been reported that PGE2 may play proinflammatory and anti-inflammatory roles by binding to EP1-EP4 receptors [ 35 , 56 , 57 ]. Via PGE2 secretion, MSCs mediate the activation of macrophage (M2) polarization and inhibit the proliferation of activated T, NK and NKT cells [ 49 , 58 ].…”

“…Via PGE2 secretion, MSCs mediate the activation of macrophage (M2) polarization and inhibit the proliferation of activated T, NK and NKT cells [ 49 , 58 ]. Recent work using the bioactive molecule PGE2 showed promise for angiogenesis functions and regenerative therapy [ 35 ].…”

“…For bioluminescence imaging (BLI), firefly luciferase (Fluc) was used for MSCs as previously described [ 35 , 36 ]. For intravital imaging, ALI mice were established by intratracheal injection of LPS.…”

Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy

“…Subsequently, 200 μL of 1 mg/mL NO prodrug, MGP, was administered via tail vein injection every other day until the end of the experiment. To monitor angiogenesis in real time in vivo, C57BL/6 albino and outbred (Nu/Nu) background Vegfr2-luciferase transgenic mice (10 weeks of age, female) were used to establish an AKI model induced by I/R injury ( Zhang et al, 2023 ; Huang et al, 2022 ). The treatment of animals and the experimental procedures of the present study adhered to the Nankai University Animal Care and Use Committee Guidelines that conform to the Guidelines for Animal Care approved by the National Institutes of Health (NIH).…”

Renal Endothelial Cell‐Targeted Extracellular Vesicles Protect the Kidney from Ischemic Injury

“…In Vegfr2‐Fluc‐KI mice, firefly luciferase (Fluc) was expressed under the promoter of vascular endothelial growth factor receptor 2 (Vegfr2) to report angiogenesis in vivo. [ 17 ] All the animal treatments and the experimental procedures of the present study were approved by the Animal Experiments Ethical Committee of Nankai University and were in accordance with the NIH Guide for the Care and Use of Laboratory Animals (approval no. 20 190 022).…”