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

Journal of Nanobiotechnology

Jun Zhang¹  Yuqiao Chang²  Zhikun Guo²  Guoqiang Hua³  Nadia Benkirane-Jessel³  Xiaohong Shen⁴  Hui Cheng⁵  Shang Chen⁵  Haoyan Huang⁶  Zongjin Li⁷  Wei Du⁸  Zhibo Han⁹  Zhong-Chao Han⁹  Ying Chang^1,10  Jiasong Cao^1,10 

[1] Department of Pain Treatment, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China;Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China;INSERM (French Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France;Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France;Nankai University School of Medicine, Tianjin, China;Nankai University School of Medicine, Tianjin, China;The Key Laboratory of Bioactive Materials, Ministry of Education, The College of Life Sciences, Nankai University, Tianjin, China;Nankai University School of Medicine, Tianjin, China;The Key Laboratory of Bioactive Materials, Ministry of Education, The College of Life Sciences, Nankai University, Tianjin, China;Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin, China;Nankai University School of Medicine, Tianjin, China;The Key Laboratory of Bioactive Materials, Ministry of Education, The College of Life Sciences, Nankai University, Tianjin, China;Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin, China;Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China;State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, China;Tianjin Key Laboratory of Blood Cell Therapy Technology, Union Stem Cell & Gene Engineering Co. Ltd., Tianjin, China;Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center for Cell Products, AmCellGene Co., Ltd., Tianjin, China;Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co., Beijing, China;Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin, China;

关键词: Prostaglandin E (PGE);    Sustained release;    Hindlimb ischemia (HI);    Angiogenesis;    Muscle regeneration;    MyoD1;    Molecular imaging;   

DOI  :  10.1186/s12951-022-01301-3

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsIn 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.ConclusionsOur 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

【 授权许可】

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