课题基金基金详情
Rho/Rock通道的阻断保护低温应激下的ASC的功能以促进长期冻存SVF-gel体内成脂的机制研究
结题报告
批准号:
82002058
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
冯晶玮
依托单位:
学科分类:
体表组织器官畸形、损伤与修复、再生
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
冯晶玮
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中文摘要
脂肪在软组织修复领域有诸多应用潜力,因其高吸收率常需多次填充,故脂肪冻存技术面临着巨大的临床需求。因脂肪冷冻生理理论匮乏,现有技术难以避免冻存后脂肪移植物坏死等并发症风险。我们发现脂肪干细胞基质胶(SVF-gel)技术通过物理处理,去除了冻存耐受差的成熟脂肪细胞,富集了冻存潜力好的脂肪来源干细胞(ASC)与细胞外基质。然而,在ASC凋亡情况水平时,冷冻SVF-gel的成脂能力却显著优于冷冻脂肪。我们发现组织冷冻,明显激活Rho/Rock信号通路主导的凋亡信号,而非坏死性炎症通道。添加凋亡抑制剂fasudil则可大幅提高冻存SVF-gel中的ASC活性,进而改善凋亡微环境与成脂。本研究围绕“阻断Rho/Rock通道可保护SVF-gel的低温应激损伤”这一发现,拟采用细胞生物学技术、蛋白生化技术、功能性显像技术等,对ASC的低温应激损伤机制和脂肪组织冷冻生理学进行阐释。
英文摘要
Autologous fat has many application potentials for soft tissue repair. Because its high absorption rate, this often requires multiple fillings, thus fat cryopreservation technology faces huge clinical needs. Due to the lack of physiological theory of fat cryopreservation, it is difficult to avoid adipocytes rupture after freeze-thaw procedure, resulting in graft necrosis and risk of complications. We found that fat product of ECM/SVF-gel (or SVF-gel) technique removes mature adipocyte that are poorly tolerated through pure physical processing, and enriches adipose-derived stem cells (ASC) and extracellular matrix indicating good cryopreservation potential. However, in the case of similar ASC activity and function, the fat-forming ability of frozen SVF-gel was significantly better than that of frozen fat. According to the analysis of inflammation patterns, when tissues are regenerated after freezing, the apoptotic signals dominated by the Rho / Rock signaling pathway are more strongly activated than the necrotic inflammatory channels. Adding apoptosis inhibitor fasudil can greatly increase the ASC activity in frozen SVF-gel, and then improve the apoptotic microenvironment and adipogenesis. This study revolves around the discovery that blocking Rho / Rock signaling protects SVF-gel from low-temperature stress injury. It is proposed to use cell biology technology, protein biochemical technology, and functional imaging technology to reduce the low-temperature stress injury of ASC. Mechanisms and Rho / Rock explain the role played by epigenetics and metabolic functions. It is intended to enrich the basic research of adipose tissue cryophysiology, and finally provide a theoretical basis for further optimization of adipose cryopreservation technique.
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DOI:10.1186/s13287-022-02774-7
发表时间:2022-03-07
期刊:Stem cell research & therapy
影响因子:7.5
作者:Guan J;Li Y;Lu F;Feng J
通讯作者:Feng J
DOI:10.1186/s40001-023-01236-x
发表时间:2023-09-15
期刊:EUROPEAN JOURNAL OF MEDICAL RESEARCH
影响因子:4.2
作者:Liu, Meiqi;Feng, Jingwei
通讯作者:Feng, Jingwei
DOI:10.2217/rme-2023-0098
发表时间:2023
期刊:Regenerative Medicine
影响因子:2.7
作者:Meiqi Liu;Feng Lu;Jingwei Feng
通讯作者:Jingwei Feng
DOI:10.1097/prs.0000000000011154
发表时间:2024-10-01
期刊:PLASTIC AND RECONSTRUCTIVE SURGERY
影响因子:3.6
作者:Guan,Jingyan;Feng,Jingwei;Lu,Feng
通讯作者:Lu,Feng
国内基金
海外基金