Establishment of human hematopoietic system model mouse for understanding the regulatory mechanisms of human hematopoiesis.

建立人类造血系统模型小鼠，以了解人类造血的调控机制。

基本信息

批准号：
18500332
负责人：
YAHATA Takashi
金额：
$ 2.57万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18500332/
关键词：
hematopoietic stern cells niche humanized mouse mesehcnymal stem cells intra-bone marrow transplantation cord blood cell cycle ヒトビモデンレマウス造血環境造血制御

项目摘要

Hematopoiesis is maintained by specificinteractions between both hematopoietic and non-hematopoietic cells. While hematopoietic stem cells (HSCs) have been extensively studied both in vitro and in vivo, little is known about the in vivo characteristics of stem cells of the non-hematopoietic component, known as mesenchymal stem cells (MSCs). Here we have visualized and characterized human MSCs in vivo following intramedullary transplantation of enhanced green fluorescent protein-marked human MSCs (eGFP-MSCs) into the bone marrow (BM) of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. During 4 to 10 weeks after transplantation, eGFP-MSCs that engrafted in murine BM integrated into the hematopoietic microenvironment (HME) of the host mouse. They differentiated into pericytes, myofibroblasts, BM stromal cells, osteocytes in bone, bone-lining osteoblasts, and endothelial cells, which constituted the functional components of the BM HME. The presence of human MSCs in murine BM resulted in increase in functionally and phenotypically primitive human hematopoietic cells. Human MSC-derived cells that reconstituted the hematopoietic microenvironment appeared to contribute to the maintenance of human hematopoiesis by actively interacting with primitive human hematopoietic cells.

造血是通过造血和非造血细胞之间的特异性造成的。虽然造血干细胞（HSC）在体外和体内都进行了广泛的研究，但对非杂质者成分的干细胞的体内特征知之甚少，被称为间充质干细胞（MSC）。在这里，我们已经在体内可视化和表征了人类MSC在体内的体内，后者在非肥胖糖尿病/严重组合的免疫缺陷（NOD/SCID）小鼠的骨髓骨髓（BM）中增强了绿色荧光蛋白标记的人MSC（EGFP-MSC）。在移植后4至10周内，植入鼠BM中的EGFP-MSC集成了宿主小鼠的造血微环境（HME）。它们分化为周细胞，肌纤维细胞，BM基质细胞，骨骼中的骨细胞，骨内骨细胞和内皮细胞，这些细胞构成了BM HME的功能成分。鼠BM中人类MSC的存在导致功能和表型原始的人类造血细胞的增加。重建造血微环境的人类MSC衍生的细胞似乎通过与原始的人类造血细胞相互作用，从而有助于维持人类造血。