[发明专利]产生细胞囊和细胞囊管的方法

说明书

本发明提供了用于在3D基质中产生细胞囊和细胞囊管的方法和组合物。

技术领域

本发明涉及产生细胞囊和细胞囊管的领域，及其方法和组合物。

背景技术

细胞边界将细胞与外部环境分开，允许和保护细胞内活动和内容物免受环境因素的不良影响。细胞边界对细胞的感知、迁移、入侵、重定位、增殖、生长、分化、与环境的交流和响应、营养和氧气的摄入、代谢废物的排除以及抵御环境压力至关重要。

多细胞生物体的细胞运动对胚胎发育(Le Douarin NM(1984)Cell migrationsin embryos.Cell 38(2):353-360；Reig G,Pulgar E,&Concha ML(2014)Cell migration:from tissue culture to embryos.Development 141(10):1999-2013；Richardson BE&Lehmann R(2010)Mechanisms guiding primordial germ cell migration:strategiesfrom different organisms.Nat Rev Mol Cell Biol 11(1):37-49)、器官稳态(AcloqueH,Adams MS,Fishwick K,Bronner-Fraser M,&Nieto MA(2009)Epithelial-mesenchymaltransitions:the importance of changing cell state in development anddisease.The Journal of clinical investigation 119(6):1438-1449)、组织再生(Bryant DM&Mostov KE(2008)From cells to organs:building polarized tissue.NatRev Mol Cell Biol 9(11):887-901)、免疫应答(Woodland DL&Kohlmeier JE(2009)Migration,maintenance and recall of memory T cells in peripheral tissues.NatRev Immunol 9(3):153-161；Weninger W,Biro M,&Jain R(2014)Leukocyte migrationin the interstitial space of non-lymphoid organs.Nat Rev Immunol 14(4):232-246)、伤口修复(Gurtner GC,Werner S,Barrandon Y,&Longaker MT(2008)Wound repairand regeneration.Nature 453(7193):314-321)以及肿瘤扩散(Friedl P&Alexander S(2011)Cancer invasion and the microenvironment:plasticity andreciprocity.Cell 147(5):992-1009；Friedl P&Wolf K(2003)Tumour-cell invasionand migration:diversity and escape mechanisms.Nat Rev Cancer 3(5):362-374；Barbolina MV,et al.(2009)Microenvironmental regulation of ovarian cancermetastasis.Cancer Treat Res 149:319-334)至关重要。三维(3D)微环境中的细胞迁移经历了异质细胞和细胞外基质(ECM)，其为运动方向提供支架和引导线索，同时基本上形成了阻碍细胞运动的环境障碍(Thiery JP,Acloque H,Huang RY,&Nieto MA(2009)Epithelial-mesenchymal transitions in development and disease.Cell 139(5):871-890；Franz CM,Jones GE,&Ridley AJ(2002)Cell migration in development anddisease.Dev Cell 2(2):153-158)。为了促进运动，细胞自适应地产生随时空变化而变化的表面连接的细胞器和隔室，包括板状伪足(Murphy DA&Courtneidge SA(2011)The'ins'and'outs'of podosomes and invadopodia:characteristics,formation andfunction.Nat Rev Mol Cell Biol 12(7):413-426)、丝状伪足(Mattila PK&LappalainenP(2008)Filopodia:molecular architecture and cellular functions.Nat Rev MolCell Biol 9(6):446-454)、伪足小体(podosome)(Tarone G,Cirillo D,Giancotti FG,Comoglio PM,&Marchisio PC(1985)Rous sarcoma virus-transformed fibroblastsadhere primarily at discrete protrusions of the ventral membrane calledpodosomes.Exp Cell Res 159(1):141-157)、侵袭性伪足(Chen WT(1989)Proteolyticactivity of specialized surface protrusions formed at rosette contact sitesof transformed cells.J Exp Zool 251(2):167-185)、泡状伪足(Fackler OT&Grosse R(2008)Cell motility through plasma membrane blebbing.J Cell Biol 181(6):879-884；Ridley AJ(2011)Life at the leading edge.Cell 145(7):1012-1022)、黏着斑(Wehrle-Haller B(2012)Structure and function of focal adhesions.Currentopinion in cell biology 24(1):116-124)、树突状伪足突起和II型上皮桥(Zani BG,Indolfi L,&Edelman ER(2010)Tubular bridges for bronchial epithelial cellmigration and communication.PLoS One 5(1):e8930)。因而，多细胞生物体中细胞重定位的机制尚不清楚。