血管内皮细胞（VECs）具有调节炎症反应、影响血管发生、促进组织再生等作用，在创面修复过程中扮演着至关重要的角色。VECs参与创面愈合的事实有助于形成新的治疗手段，在促进受损组织血运重建、加强创面愈合、恢复器官功能等临床应用方面有着巨大潜力。鉴于VECs来源有限，获取大量可分化为VECs的干细胞已成为重点研究内容。脂肪干细胞（ADSCs）来源丰富、易于获取、扩增快速，被证实具备多向分化能力。因此，研究ADSCs向VECs分化的机制，可开拓其用于创面愈合领域的新未来。作者主要针对ADSCs和VECs的鉴定、诱导分化方法、潜在的分化机制及未来可能的应用领域进行综述。

[1] ZUK P A,ZHU M,ASHJIAN P,et al.Human adipose tissue is a source of multipotent stem cells[J].Mol Biol Cell,2002,13(12):4279-4295.
[2] 李莹,李小兵.人脂肪干细胞的生物学特性及分化研究[J].医学信息,2020,33(1):89-93.
[3] ZUK P A.The adipose-derived stem cell:looking back and looking ahead[J].Mol Biol Cell,2010,21(11):1783-1787.
[4] HONNEGOWDA T M,KUMAR P,UDUPA E G P,et al.Role of angiogenesis and angiogenic factors in acute and chronic wound healing[J].Plastic and Aesthetic Research,2015,2(5):243-249.
[5] 张立明,蔡洁云,潘福强,等.脂肪干细胞在炎性创面中的应用及前景[J].中国组织工程研究,2019,23(25):4089-4093.
[6] BOURIN P,BUNNELL B A,CASTEILLA L,et al.Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells:a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT)[J].Cytotherapy,2013,15(6):641-648.
[7] 吴青兰,成俊芬.VEGF、ICAM-1和NO与支气管哮喘的相关性研究进展[J].现代医学,2019,47(9):1169-1172.
[8] 殷杰,马珍妮,赵小娟,等.人外周血来源的过度生长内皮细胞的分离、培养及鉴定[J].中国实验血液学杂志,2014,22(6):1711-1715.
[9] COLAZZO F,CHESTER A H,TAYLOR P M,et al.Induction of mesenchymal to endothelial transformation of adipose-derived stem cells[J].J Heart Valve Dis,2010,19(6):736-744.
[10] 刘琳,张亚,周云,等.脂肪源干细胞向血管内皮细胞的分化[J].中国组织工程研究,2013(23):4224-4231.
[11] SHANG T,LI S J,ZHANG Y,et al.Hypoxia promotes differentiation of adipose-derived stem cells into endothelial cells through demethylation of ephrinB2[J].Stem Cell Res Ther,2019,10(1):1-12.
[12] 焦自钊,薛武军,田晓辉,等.ADSCs与HUVECs体外共培养促进HUVECs增殖及成血管化作用[J].西安交通大学学报(医学版),2016,37(4):493-499.
[13] 石志康,张胜利,赵敏利,等.脂肪干细胞和血管内皮细胞共培养复合脱细胞基质材料修复兔尿道缺损的实验研究[J].临床小儿外科杂志,2020,19(4):310-316.
[14] 李江璇,肖丽玲,李升红,等.VEGF基因转染脂肪干细胞后上清液对皮肤成纤维细胞及脐静脉血管内皮细胞的影响[J].中国病理生理杂志,2019,35(3):542-548.
[15] 伞光,宋佳.血小板衍生内皮细胞生长因子转染脂肪间充质干细胞促进移植脂肪血管化[J].中国组织工程研究,2015,19(41):6600-6605.
[16] MUSTONEN T,ALITALO K.Endothelial receptor tyrosine kinases involved in angiogenesis[J].J Cell Biol,1995,129(4):895-898.
[17] CHENG N,BRANTLEY D M,LIU H,et al.Blockade of EphA receptor tyrosine kinase activation inhibits vascular endothelial cell growth factor-induced angiogenesis[J].Mol Cancer Res,2002,1(1):2-11.
[18] KIM I,RYU Y S,KWAK H J,et al.EphB ligand,ephrinB2,suppresses the VEGF- and angiopoietin-1-induced Ras/mitogen-activated protein kinase pathway in venous endothelial cells[J].Faseb J,2002,16(7):1126-1127.
[19] TIMMERS L,LIM S K,ARSLAN F,et al.Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium[J].Stem Cell Res,2008,1(2):129-137.
[20] MAO L,LI J,CHEN W X,et al.Exosomes decrease sensitivity of breast cancer cells to adriamycin by delivering microRNAs[J].Tumor Biol,2016,37(4):5247-5256.
[21] RATAJCZAK J,MIEKUS K,KUCIA M,et al.Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors:evidence for horizontal transfer of mRNA and protein delivery[J].Leukemia,2006,20(5):847-856.
[22] 张桂龙,陈陆馗,李炳乾,等.人源神经干细胞来源外泌体的提取鉴定及内吞作用[J].东南大学学报(医学版),2017,36(6):984-989.
[23] 张静,易阳艳,阳水发,等.脂肪干细胞来源外泌体对人脐静脉血管内皮细胞增殖、迁移及管样分化的影响[J].中国修复重建外科杂志,2018,32(10):1351-1357.
[24] 张亚,周云,朱璟晶,等.脂肪干细胞分化成血管内皮细胞前后miRNA的差异表达[J].江苏医药,2015(8):880-883,864.
[25] KACHGAL S,PUTNAM A J.Mesenchymal stem cells from adipose and bone marrow promote angiogenesis via distinct cytokine and protease expression mechanisms[J].Angiogenesis,2011,14(1):47-59.
[26] GU H J,GUO F F,ZHOU X,et al.The stimulation of osteogenic differentiation of human adipose-derived stem cells by ionic products from akermanite dissolution via activation of the ERK pathway[J].Biomaterials,2011,32(29):7023-7033.
[27] KASIR R,VERNEKAR V N,LAURENCIN C T.Regenerative engineering of cartilage using adipose-derived stem cells[J].Regen Eng Transl Med,2015,1(1-4):42-49.
[28] RAY P,TORCK A,QUIGLEY L,et al.Comparative transcriptome profiling of the human and mouse dorsal root ganglia:an RNA-seq-based resource for pain and sensory neuroscience research[J].Pain,2018,159(7):1325-1345.
[29] GERMAN S J,BEHBAHANI M,MIETTINEN S,et al.Proliferation and differentiation of adipose stem cells towards smooth muscle cells on poly(trimethylene carbonate) membranes[J].Macromol Symp,2013,334(1):133-142.
[30] SUN Y Y,LU B L,DENG J C,et al.IL-7 enhances the differentiation of adipose-derived stem cells toward lymphatic endothelial cells through AKT signaling[J].Cell Biol Int,2019,43(4):394-401.
[31] HELLSTROM M,PHNG L K,HOFMANN J J,et al.Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis[J].Nature,2007,445(7129):776-780.
[32] KIM J H,PEACOCK M R,GEORGE S C,et al.BMP9 induces EphrinB2 expression in endothelial cells through an Alk1-BMPRII/ActRII-ID1/ID3-dependent pathway:implications for hereditary hemorrhagic telangiectasia type II[J].Angiogenesis,2012,15(3):497-509.
[33] 殷令妮,陈德宣.PI3K/Akt通路在低氧诱导脂肪干细胞增殖和向内皮细胞分化中的作用[J].中国组织工程研究,2020,24(19):3004-3009.
[34] VOLZ A C,HUBER B,KLUGER P J.Adipose-derived stem cell differentiation as a basic tool for vascularized adipose tissue engineering[J].Differentiation,2016,92(1-2):52-64.
[35] DOLDERER J H,MEDVED F,HAAS R M,et al.Angiogenesis and vascularisation in adipose tissue engineering[J].Handchir Mikrochir P,2013,45(2):99-107.
[36] KAYABOLEN A,KESKIN D,AYKAN A,et al.Native extracellular matrix/fibroin hydrogels for adipose tissue engineering with enhanced vascularization[J].Biomed Mater,2017,12(3):035007.
[37] PARK I S,KIM S H,JUNG Y,et al.Endothelial differentiation and vasculogenesis induced by three-dimensional adipose-derived stem cells[J].Anat Rec (Hoboken),2013,296(1):168-177.
[38] MAZINI L,ROCHETTE L,ADMOU B,et al.Hopes and limits of adipose-derived stem cells (ADSCs) and mesenchymal stem cells (MSCs) in wound healing[J].Int J Mol Sci,2020,21(4):1306.