アクティブボード・2017年9月
・・・・・2017年 8月31日更新・・・・・
研究発表を行った学会;
2nd Kumamoto IRCMS International Symposium and 17th Kumamoto AIDS Seminar
2016年10月31日〜11月 2日(熊本県民交流会間-Parea、熊本)
タイトル;Reconstitution of human bone marrow niche for better maintenance of human hematopoiesis in vivo.
発表者;Xiaomin Feng 氏
(熊本大学 国際先端医学研究機構(IRCMS))
要旨;
Xenograft transplantation have represented so-far best approach to study human phyosiology and pathophysiology, and significantly advanced our understanding of human hematopoiesis hemato-immuno system in health and disease. Although a number of immunodeficient mouse strains have been developed for xenograft models, full maintenances of human hematopoiesis has not been fully achieved yet. We have previously shown that in vitro cultured human bone marrow (BM) mesenchymal stromal cells (MSCs), one of putative BM microenvironmental components, can be ex vivo and in vivo remodeled to human bone organ that is able to maintain mouse hematopoietic stem cells (HSCs) (Scotti et. al., PNAS 2014). However, it has not been tested yet whether the human bone organ can sustain functional human HSCs and hematopoiesis. Here, we showed that upon ex vivo differentiation of human BM MSCs (BM-MSCs) into hypertrophic cartilage and in vivo implantation into immunodeficient mice, human BM MSCs developed to a fully mature bone organ that contained functional human HSCs with self-renewal and multilineage differentiation capacity upon serial transplantation. Furthermore, as major BM niche components are not only MSCs but also vascular endothelial cells, we co-cultured MSCs with human umbilical vein endothelial cells (HUVECs) and observed the assembly of human microvessels were initialed and self-organized efficiently within BM-MSCs-derived cartilage, indicating potential cellular communication between MSCs and HUVECs, and possible approach for better human HSC niche remodeling in vivo. Our results suggest that the humanized ossicle with functional MSCs will provide a powerful approach to study normal and malignant human BM niche components, as well as to test/develop new drugs for pre-clinical trial.