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1. 发明申请

WO2005023982A2 METHODS FOR ENHANCING ENGRAFTMENT OF PURIFIED HEMATOPOIETIC STEM CELLS IN ALLOGENIC RECIPIENTS 审中-公开
标题翻译：增强造血干细胞在同种异体受体中的增殖方法
公开(公告)号：WO2005023982A2
公开(公告)日：2005-03-17
申请号：PCT/US2004016843
申请日：2004-05-28
申请人： UNIV OF LOUISVILLE RES FOUNDAT , ILDSTAD SUZANNE T
发明人： ILDSTAD SUZANNE T
IPC分类号： C12N
CPC分类号： A61K35/28 , A61K31/66 , A61K35/15 , A61K35/17 , A61K38/193 , A61K41/00 , A61K45/06
摘要： CD8 /TCR bone marrow cells facilitate engraftment of hernapoietic stem cells (HSQ in allogeneic recipients without causing graft versus host disease. The present invention identifies the main subpopulation (55-65 %) of CD8 /TCR facilitating cells (FQ as plasmacytoid precursor dendritic cells (p-preDC). The present invention notably demonstrates that FC and p-preDC share many phenotypic, morphological, and functional features, including IFN-alpha production, activation and survival after stimulation, and expansion and maturation after FIO-Ligand (FL) treatment. FLmobilized FC, the majority of which express a pre- DC phenotype, facilitate HSC engraftment. Although p-preDC significantly enhance HSC engraftment, they do so with less efficiency than FC. The present invention for the first time defines a direct functional role for p-preDC in HSC engraftment and will have a significant impact on strategies to design effective facilitating cell-based therapies for transplantation.
摘要翻译： CD8 + / TCR < - >骨髓细胞有利于植入人造血干细胞（同种异体受体中的HSQ，而不引起移植物抗宿主病），本发明鉴定了CD8 + / TCR的主要亚群（55-65％）促进细胞（FQ作为浆细胞样前体树突细胞（p-preDC））本发明特别表明FC和p-preDC具有许多表型，形态和功能特征，包括IFN-α产生，刺激后的活化和存活，FLO-Ligand（FL）处理后的扩增和成熟FLMobilized FC，其中大部分表达pre-DC表型，促进HSC植入，尽管p-preDC显着增强HSC植入，但效率低于FC。本发明首次定义了p-preDC在HSC植入中的直接功能作用，并且将对设计有效促进基于细胞的移植疗法的策略具有显着影响。

2. 发明申请

WO2005001040A3 NON-LETHAL CONDITIONING METHODS FOR CONDITIONING A RECIPIENT FOR BONE MARROW TRANSPLANTATION 审中-公开
标题翻译：用于骨髓移植受体调节的非牙齿调节方法
公开(公告)号：WO2005001040A3
公开(公告)日：2005-04-14
申请号：PCT/US2004017051
申请日：2004-05-28
申请人： UNIV OF LOUISVILLE RES FOUNDAT , ILDSTAD SUZANNE T
发明人： ILDSTAD SUZANNE T
IPC分类号： A61K31/711 , A61K39/395 , C12N20060101
CPC分类号： A61K31/675 , A61K2039/505 , A61K2039/507 , C07K16/2809 , C07K16/2815
摘要： Mixed chimerism induces donor-specific transplantation tolerance to organ allografts. In this invention, recipient B10 (h2 ) mice were pretreated in vivo with anti-abeta-TCR and anit-CD8 mABs 3 days before total body irradiation (TBI) and transplanted with 15 X 10 allogenic (B10.BR; H2k) marrow cells. Engraftment occurred in 20%, 75% and 94% of animals conditioned with 100, 200 or 300 cGy TBI one month post bone marrow transplant (BMT), respectively. Animals without donor T cells lost their chimerism gradually within 6 months and rejected both donor and third-party skin grafts. In animals with donor T cell production, chimerism remained stable for >= 6 months and donor skin grafts were accepted. In the animals without donor T cell production, none of the expected stages of T cell development were present in the thymus, while in those with donor T cell production they were. Moreover, clonal deletion of Vbeta 5.1/2 and Vbeta 11 CD8 and CD4 T cells occurred only in chimeras with donor T cell production. These results show for the first time that donor T cell production plays a critical role in the maintenance of durable chimerism and induction of trnaplantation tolerance and is directly correlated with deletion of potentially autoreactive cells.
摘要翻译：混合嵌合体诱导供体特异性移植对器官同种异体移植的耐受性。在本发明中，在全身照射（TBI）前3天，用抗-Teta-TCR和anit-CD8mABs在体内预处理受体B10（h2b）小鼠，并用15×10 6同种异体移植（B10）。 BR; H2k）骨髓细胞。在骨髓移植（BMT）一个月后分别在100,200或300cGy TBI条件下进行移植的20％，75％和94％的移植物。没有供体T细胞的动物在6个月内逐渐失去嵌合体，并拒绝供体和第三方皮肤移植物。在具有供体T细胞产生的动物中，嵌合体保持稳定> = 6个月，并且接受供体皮肤移植物。在没有供体T细胞生产的动物中，T细胞发育的预期阶段都不存在于胸腺中，而在具有供体T细胞生产的那些中。此外，Vbeta 5.1 / 2 +和Vbeta 11 + CD8和CD4T细胞的克隆缺失仅在具有供体T细胞产生的嵌合体中发生。这些结果首次表明，供体T细胞的产生在维持持久的嵌合体和诱导trnaplantation耐受中起关键作用，并与潜在的自身反应性细胞的缺失直接相关。

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