Properties of Immune-Privileged STO-Progenitor Cells

免疫特权 STO 祖细胞的特性

基本信息

批准号：
7193735
负责人：
HYAM L LEFFERT
金额：
$ 23.18万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-15 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7193735
关键词：
Address Adult Allogenic Animals Antigens Axon Biochemistry Biological Biological Models C57BL/6 Mouse CD34 gene CD80 Antigens CD80 gene Cell Communication Cell Density Cell Differentiation process Cell Line Cells Class Complementary DNA Condition Duct (organ) structure Embryo Engraftment Fibrous capsule of kidney Flow Cytometry Genetic Genetic Transcription German population Goals Growth Factor Haplotypes Hepatic Hepatocyte Homologous Transplantation Human Image Immune Immunity Immunofluorescence Immunologic Immunohistochemistry Immunologics Immunosuppression In Vitro Inbred BALB C Mice Inbred F344 Rats Injury Kidney Knock-out Label Lesion Liver MHC Class I Genes Methods Mixed Lymphocyte Culture Test Modeling Molecular and Cellular Biology Monitor Mus Phenotype Procedures Property Proteins Rat-1 Rattus Reagent Research Signal Transduction Skin graft Source Spinal Cord Spinal Cord Lesions Staining method Stains Standards of Weights and Measures Stem cell transplant Stem cells Structure Surface Swiss Mice System TNFSF6 gene Testing Therapeutic immunosuppression Time Tissue Grafts Transgenic Mice Transgenic Organisms Translating Transplantation Transplantation Immunology Western Blotting Wild Type Mouse Xenograft procedure base density extracellular immunogenicity immunosuppressed in vivo in vivo Model injured intrahepatic kidney allograft new growth novel pressure progenitor stem transplantation medicine

项目摘要

DESCRIPTION (provided by applicant): The long-term objectives of this R21 application are to characterize several key biological and immunological properties of embryonic Swiss mouse STO- and STO cell-derived (SCO) progenitor cell lines to determine the utility of these cells as novel model systems of progenitor cell differentiation and engraftment into non- immunosuppressed mammalian hosts. Intrahepatic xenografts of STO and SCO cell lines survive without immunosuppression for at least three months in either dipeptidylpeptidase IV-negative (DPPIV) German F344 rats or in their wild type DPPIV* counterparts. An EGFP-labeled SCO cell line (3(8)21-EGFP) also survives without immunosuppression for at least one month as a subcapsular renal allograft in adult C57BL/6J mice, and as a subdural xenograft in C3-lesioned spinal cords in adult F344 rats. Donor mouse STO and SCO cells display phenotypes (MHC class I+[LOW1 (H-2Kd[LOW]) / class ll-negative (l-AdH); CD80- and CD86-negative) consistent with immune privilege; they differentiate into hepatic and axon-inducing neuroglial lineages in the rat liver and lesioned rat spinal cord models in vivo, respectively, and into duct-like structures under mouse renal capsules. These novel and unexpected findings suggest the hypothesis that STO and SCO cells might provide immune-privileged pluripotential progenitor cell-like material for universal tissue grafts in non-immunosuppressed recipients. Accordingly, STO and SCD cells will be used to: 1] investigate in vitro hepatocytic progenitor cell potential; 2] investigate in vivo hepatocytic progenitor cell potential and allogeneic survival in non-immunosuppressed wild type and genetically injured knockout and transgenic H-2b mice; 3] characterize immunogenicity and antigenicity in non-immunosuppressed allogeneic mice; and, 4] delineate mechanisms of non-expression of costimulatory molecules CD80 and CD86. Standard procedures of cell and molecular biology, biochemistry, immunology, transplantation and mouse genetics will be exploited, along with real-time EGFP imaging. The properties of the donor cells and recipient models examined thus far suggest novel possibilities for developing nonhuman sources of immune privileged progenitor cells for transplantation without immunosuppression. As a result of these proposed studies, new cellular reagents will be available for new models for regenerative and transplantation medicine.

描述（由申请人提供）：该 R21 申请的长期目标是表征瑞士小鼠胚胎 STO 和 STO 细胞衍生 (SCO) 祖细胞系的几个关键生物学和免疫学特性，以确定这些细胞作为祖细胞分化和植入非免疫抑制哺乳动物宿主的新模型系统。在二肽基肽酶 IV 阴性 (DPPIV) 德国 F344 大鼠或其野生型 DPPIV* 大鼠中，STO 和 SCO 细胞系的肝内异种移植物在没有免疫抑制的情况下存活至少三个月。 EGFP 标记的 SCO 细胞系 (3(8)21-EGFP) 在成年 C57BL/6J 小鼠中作为被膜下同种异体肾移植物以及在成人 C3 损伤脊髓中作为硬膜下异种移植物，在没有免疫抑制的情况下也能存活至少一个月F344 大鼠。供体小鼠 STO 和 SCO 细胞表现出与免疫豁免一致的表型（MHC I 类+[LOW1 (H-2Kd[LOW])/II 类阴性 (l-AdH)；CD80 和 CD86 阴性）；它们分别在体内大鼠肝脏和受损大鼠脊髓模型中分化为肝脏和轴突诱导神经胶质细胞谱系，并在小鼠肾被膜下分化为导管样结构。这些新颖且出乎意料的发现表明，STO 和 SCO 细胞可能为非免疫抑制受体的通用组织移植物提供免疫特权的多能祖细胞样材料。因此，STO和SCD细胞将用于：1]研究体外肝细胞祖细胞潜力； 2]研究非免疫抑制野生型和基因损伤的敲除和转基因H-2b小鼠体内肝细胞祖细胞潜力和同种异体存活； 3]表征非免疫抑制同种异体小鼠的免疫原性和抗原性； 4]描绘了共刺激分子CD80和CD86的不表达机制。将利用细胞和分子生物学、生物化学、免疫学、移植和小鼠遗传学的标准程序以及实时 EGFP 成像。迄今为止检查的供体细胞和受体模型的特性表明，开发非人类来源的免疫特权祖细胞用于无免疫抑制移植的新可能性。这些拟议研究的结果是，新的细胞试剂将可用于再生和移植医学的新模型。