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Generation of rat blood vasculature and hematopoietic cells in rat-mouse chimeras by blastocyst complementation

Journal of Genetics and Genomics 2020年第5期47卷 249-261页

作者： Xiaomin Wang Hui Shi Juanjuan Zhou Qingjian Zou Quanjun Zhang Shixue Gou Pengfei Chen Lisha Mou Nana Fan Yangyang Suo Zhen Ouyang Chengdan Lai Quanmei Yan Liangxue Lai CAS Key Laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou510530China University of Chinese Academy of Sciences Beijing100049China Guangzhou Regenerative Medicine and Health Guangdong Laboratory(GRMH-GDL) Guangzhou510005China Institute for Stem cell and Regeneration Chinese Academy of SciencesBeijing100101China Research Unit of Generation of Large Animal Disease Models Chinese Academy of Medical Sciences(2019RU015)Guangzhou510530China School of Biotechnology and Health Sciences Wuyi UniversityJiangmen529020China Shenzhen Xenotransplantation Medical Engineering Research and Development Center Institute of Translational MedicineShenzhen University Health Science CenterShenzhen University School of MedicineFirst Affiliated Hospital of Shenzhen UniversityShenzhen Second People's HospitalShenzhen518035China Department of Central Laboratory Shenzhen Longhua District Central HospitalShenzhen518110China School of Life Sciences University of Science and Technology of ChinaHefei230027China Joint School of Life Sciences Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical UniversityGuangzhou511436China

Interspecies chimera through blastocyst complementation could be an alternative approach to create human organs in animals by using human pluripotent stem cells.A mismatch of the major histocompatibility complex of vascular endothelial cells between the human and host animal will cause graft rejection in the transplanted organs.Therefore,to achieve a transplantable organ in animals without rejection,creation of vascular endothelial cells derived from humans within the organ is necessary.In this study,to explore whether donor xeno-pluripotent stem cells can compensate for blood vasculature in host animals,we generated rat-mouse chimeras by injection of rat embryonic stem cells(rESCs)into mouse blastocysts with deficiency of Flk-1 protein,which is associated with endothelial and hematopoietic cell development.We found that rESCs could differentiate into vascular endothelial and hematopoietic cells in the rat-mouse chimeras.The whole yolk sac(YS)of Flk-1^EGFP/ECFP rat-mouse chimera was full of rat blood vasculature.Rat genes related to vascular endothelial cells,arteries,and veins,blood vessels formation process,as well as hematopoietic cells,were highly expressed in the YS.Our results suggested that rat vascular endothelial cells could undergo proliferation,migration,and self-assembly to form blood vasculature and that hematopoietic cells could differentiate into B cells,T cells,and myeloid cells in rat-mouse chimeras,which was able to rescue early embryonic lethality caused by Flk-1 deficiency in mouse.

关键词： Blastocyst complementation Interspecies chimera Intraspecies chimera Flk-1 Vascular endothelial cell hematopoietic cell

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Study on the Protective Effects of Compound Blood-activating Soup on Bone Marrow hematopoietic cells in Acute Radiation Injured Mice

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1997年第4期17卷 225-228页

作者：刘文励肖侃艳周剑锋何美冬孙汉英唐锦治 Department of Hematology Tongji Hospital Tongji Medical University Wuhan

After irradiation with 8 Gy 60Coγ-ray,mice were immediaterly given intraperitoneal injection of 200 mg 100 % compound blood-activating soup twice a day. On the 3rd and 7th day, the P53 gene expression of bone marrow hematopoietic cells in Chinese drug group was found to be higher than that in normal group, and it was also significantly higher than that in control group. The expression level of GADD153 gene which was not expressed in normal group was much lower in Chinese drug group than that in control group. On the 7th day after irradiation, the P53 and GADD153 gene expression levels of splenic mononuclear cells were consistent with those of bone marrow hematopoietic cells both in Chinese drug group and control group. On the 3rd and 7th day, the bone marrow hematopoietic tissue volume in Chinese drug group was higher than that in control group, with no difference found between the two groups. While on the 14th day, the difference became significant (P＜0. 01). The results showed that commonly used blood-activating and stasis-eliminating drugs may strengthen .the viability of hematopoietic cells and promote the rehabilitation of hematopoiesis by inducing wt-P53 expression to block the bone marrow hematopoietic cells in G1 phase, during which DNA could be repaired.

关键词： acute radiation injury hematopoietic cell P_53 gene GADD_153 gene blood-activating and stasis-eliminating Chinese drugs

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nduced pluripotent stem cell （iPSCs） and their application n immunotherapy

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cellular & Molecular Immunology 2014年第1期11卷 17-24页

作者： Zhengping Jiang Yanmei Han Xuetao Cao National Key Laboratory of Medical Immunology & Institute of Immunology Second Military Medical University Shanghai China

The ever-improving technology to generate induced pluripotent stem cells （iPSCs） has increased their potential use as novel candidates for disease modeling, drug screening, regenerative medicine and cell therapy. Indeed, iPSCs offer extensive capacity for self-renewal without the ethical concerns faced by embryonic stem cells （ESCs）. With respect to potential applications in the immune system, many studies provide evidence to support that there are exclusive advantages to using iPSCs over other systems. Both hematopoietic stem cells and several types of mature immune cells have successfully been reprogrammed to iPSCs and vice versa, paving a path toward our ability to effectively model patient-specific diseases and provide potentially alternative cell sources for transfusion medicine. Despite these potential advances, some limitations regarding the use of iPSCs in the clinic still remain, including the immunogenicity of iPSCs and their derivatives, which is currently under debate in the field. In this review, we mainly focus on discussing the recent progress being made in the latest differentiation methods and clinical implications of iPSCs with respect to the immune system. Additionally, current issues regarding the clinical application of iPSCs are addressed, especially the controversy surrounding immunogenicity, along with various other perspectives.

关键词： differentiation hematopoietic cell immunogenicity immunotherapy induced pluripotent stem cells

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