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Complete canine spinal cord transection model: a large animal model for the translational research of spinal cord regeneration

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Science China(Life Sciences) 2018年第1期61卷 115-117页

作者： Sufang Han Xing Li Zhifeng Xiao Jianwu Dai State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences

Traumatic spinal cord injury (SCI) usually results in devastating neurologic deficits and disability. In the United States,approximately 12,500 new cases are reported each year, while an estimated 100,000–140,000 new cases occur every year in China (National Spinal Cord Injury Statistical Center, 2016).Spinal cord injuries are highly disabling and primarily affect young adults, and therefore create great psychological and financial burden on the affected individuals and their families.

关键词：动物模型绳索翻译新生犬损害成年人案例

Transplantation of adult spinal cord grafts into spinal cord transected rats improves their locomotor function

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Science China(Life Sciences) 2019年第6期62卷 725-733页

作者： He Shen Xi Chen Xing Li Ke Jia Zhifeng Xiao Jianwu Dai Key Laboratory for Nano-Bio Interface Research Division of Nanobiomedicine Suzhou Institute of Nano-Tech and Nano-Bionics Chinese Academy of Sciences Suzhou 215123 China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China Shigatse Branch Xinqiao Hospital Army Medical University (Third Military Medical University) Shigatse 857000 China Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan Province Xiangya Hospital Central South University Changsha 410008 China

Grafted embryonic central neural tissue pieces can recover function of hemisected spinal cord in neonatal rats and promote axonal growth in adults. However, spinal cord segments from adults have not been used as donor segments for allogeneic transplantation. Here, we utilized adult spinal cord tissue grafts(aSCGs) as donor constructs for repairing complete spinal cord injury(SCI). Moreover, to provide a favourable microenvironment for SCI treatment, a growth factor cocktail containing three growth factors(brain-derived neurotrophic factor, neurotrophin-3 and vascular endothelial growth factor), was applied to the aSCG transplants. We found that the locomotor function was significantly improved 12 weeks after transplantation of aSCGs into the spinal cord lesion site in adult rats. Transplantation of aSCGs combined with these growth factors enhanced neuron and oligodendrocyte survival and functional restoration. These encouraging results indicate that treatment of complete SCI by transplanting aSCGs, especially in the presence of growth factors, has a positive effect on motor functional recovery, and therefore could be considered as a possible therapeutic strategy for SCI.

关键词： spinal cord injury (SCI) transplantation adult spinal cord grafts (aSCGs) function recovery adult host transection

Functional biomaterial-based regenerative microenvironment for spinal cord injury repair

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National Science Review 2017年第4期4卷 530-532页

作者： Bing Chen Zhifeng Xiao Yannan Zhao Jianwu Dai State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences

Spinal cord injury(SCI)often leads to the serious loss of motor and sensory functions below the level of the lesion.The etiology of SCI is mainly traumatic,caused by events such as car accidents and falls.It remains a... 详细信息

关键词： Functional biomaterial-based regenerative microenvironment for spinal cord injury repair SCI CBD

Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women:a randomized,controlled trial

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Science China(Life Sciences) 2024年第1期67卷 113-121页

作者： Hui Zhu Taishun Li Peizhen Xu Lijun Ding Xianghong Zhu Bin Wang Xiaoqiu Tang Juan Li Pengfeng Zhu Huiyan Wang Chenyan dai Haixiang Sun Jianwu Dai Yali Hu Department of Obstetrics and Gynecology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Biostatistics Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Gynecology Changzhou Maternal and Child Health Care HospitalChangzhou Medical CenterNanjing Medical UniversityChangzhou 213004China Clinical Center for Stem Cell Research Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Hematology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100190China

Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far.To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical trial.Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January 2020.The per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control group.The ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)vs.control group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis.The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed.In conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates,and this therapy was relatively

关键词： intrauterine adhesion Asherman’s syndrome uterine infertility autologous bone marrow stem cells transplantation endometrial regeneration ongoing pregnancy rate

需求牵引、核心技术驱动的生物经济——从再生医学角度谈生物经济的高质量发展

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学术前沿 2022年第14期 27-36页

作者：戴建武中国科学院遗传与发育生物学研究所

未来10到20年,生物经济体量预计可达2万亿到4万亿美元,其中将近一半将来自医疗卫生。人类健康需求将引导核心生物技术的持续创新与突破,后者将不断满足人类健康需求和经济发展。再生医学是以生物材料为核心、以再生因子及干细胞为重要元... 详细信息

未来10到20年,生物经济体量预计可达2万亿到4万亿美元,其中将近一半将来自医疗卫生。人类健康需求将引导核心生物技术的持续创新与突破,后者将不断满足人类健康需求和经济发展。再生医学是以生物材料为核心、以再生因子及干细胞为重要元素,通过重建再生微环境来修复损伤的组织器官。再生医学关键技术的不断突破正在让一些不治之症变成可治之症,也进一步推动人体所有组织器官修复乃至体外制造成为可能。以人体组织器官护理、修复及置换等为主要业务的“人体4S店”正在变成现实,它将带来比汽车4S店更巨大的经济体量。要加速再生医学核心技术的转化与产业的发展,必须构建促进再生医学产业发展的微环境,即通过打造产业集群形成从原料到临床服务的产业链,配套以政策及产业基金扶持、人才培养、监管政策研究、知识产权服务、产品检测及注册服务等重要要素。

关键词：再生医学生物经济组织器官修复人体4S店

Biomaterials and tissue regeneration

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Biomaterials and tissue regeneration

Injectable collagen scaffold promotes swine myocardial infarction recovery by long-term local retention of transplanted human umbilical cord mesenchymal stem cells

中国神经科学学会第十届全国学术会议

作者： Jianwu Dai Institute of Genetics and Developmental Biology Chinese Academy of Sciences

Injuries to peripheral nerves result in loss of motor,sensory and autonomic functions.Peripheral nervous system injury can result in functional loss and decreased quality of life.We have developed a targeting repair system by creating specific binding between NGF and collagen avoiding diffusion.In animal models such as the subcutaneous implantation model,ear dermal ischemic ulcer model,and sciatic nerve crush model,the targeting repair system could retain NGF at the nerve injured site for a longer time to promote the regeneration of peripheral nerves.Unlike the peripheral nervous system,the regeneration ability is extremely limited in adult mammalian CNS.We constructed an efficient brain-derived neurotrophic factor BDNF delivery system including collagen-binding BDNF and linear ordered collagen scaffolds（LOCS）.Using the rat hemisection SCI model,we found that LOCS loaded with CBD-BDNF significantly improved the regeneration of CNS and the SCI recovery evaluated by the Basso,Beattie,and Bresnahan（BBB） scale and immunohistochemical staining with anti-neurofilament antibody.

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Science China(Life Sciences) 2021年第2期64卷 269-281页

作者： Qiang Wangn Xiaojun He Bin Wang Jun Pan Chunying Shi Jie Li Liudi Wang Yannan Zhao Jianwu Dai Dongjin Wang Department of Thoracic and Cardiovascular Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Center for Clinical Stem Cell Research the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Department of Human Anatomy Histology and EmbryologySchool of Basic MedicineQingdao UniversityQingdao 266021China Department of Cardiology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100190China

Stem cell therapy is an attractive approach for recovery from myocardial infarction(MI)but faces the challenges of rapid diffusion and poor survival after transplantation.Here we developed an injectable collagen scaffold to promote the long-term retention of transplanted cells in chronic MI.Forty-five minipigs underwent left anterior descending artery(LAD)ligation and were equally divided into three groups 2 months later(collagen scaffold loading with human umbilical mesenchymal stem cell(hUMSC)group,hUMSC group,and placebo group(only phosphate-buffered saline(PBS)injection)).Immunofluorescence staining indicated that the retention of transplanted cells was promoted by the collagen scaffold.Echocardiography and cardiac magnetic resonance imaging(CMR)showed much higher left ventricular ejection fraction(LVEF)and lower infarct size percentage in the collagen/hUMSC group than in the hUMSC and placebo groups at 12 months after treatment.There were also higher densities of vWf-,α-sma-,and cTnT-positive cells in the infarct border zone in the collagen/cell group,as revealed by immunohistochemical analysis,suggesting better angiogenesis and more cardiomyocyte survival after MI.Thus,the injectable collagen scaffold was safe and effective on a large animal myocardial model,which is beneficial for constructing a favorable microenvironment for applying stem cells in clinical MI.

关键词： injectable collagen scaffold mesenchymal stem cell MI

Effects of splice sites on the intron retention in histamine H_3 receptors from rats and mice

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Journal of Genetics and Genomics 2009年第8期36卷 475-482页

作者： Wenyong Ding Lin Lin Feng Ren Hanfa Zou Ziyuan Duan Jianwu Dai Department of Biochemistry and Molecular Biology Dalian Medical University Dalian 116044 China Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100080 China National Chromatographic Research and Analysis Center Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 China

In the alternative splicing, intron retention, of histamine H3 receptors in rats and mice, the short transcript isoforms that are excised alternatively spliced introns are easily detected in a very low level in rats and are undetectable in mice using the regular PCR protocol. The retained introns have common 5＇ splice site and different 3＇ splice sites. The detailed mechanism for the special alternative splicing remains largely unclear. In this study, we developed a minigene splicing system to recapitulate natural alternative splicing of the receptors and investigated the effects of 5＇ and 3＇ splice sites on intron retention in HeLa cells. Mutating weak 5＇ and 3＇ splice sites of the alternatively spliced introns toward the canonical consensus sequences promoted the splicing of the corresponding introns in rat and mouse minigenes. The effect of splice site strength was context-dependent and much more sigiaificant for the 3＇ splice site of the longer alternative intron than for the 3＇ splice site of the shorter alternative intron and the common 5＇ splice sites; it was also more significant in the rat minigene than in the mouse minigene. Mutating the 3＇ splice site of the longer alternative intron resulted in almost complete splicing of the intron and made the corresponding isoform to become the nearly exclusive transcript in the rat minigene.

关键词： histamine H3 receptor （H3R） altemative splicing intron retention splice site minigene

The Three-Dimensional Collagen Scaffold Improves the Sternness of Rat Bone Marrow Mesenchymal Stem Cells

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Journal of Genetics and Genomics 2012年第12期39卷 633-641页

作者： Sufang Han Yannan Zhao Zhifeng Xiao Jin Han Bing Chen Lei Chen Jianwu Dai State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of Sciences University of Chinese Academy of Sciences

Mesenchymal stem cells （MSCs） show the great promise for the treatment of a variety of diseases because of their self-renewal and multipotential abilities. MSCs are generally cultured on two-dimensional （2D） substrate in vitro. There are indications that they may simultaneously lose their sternness and multipotentiality as the result of prolonged 2D culture. In this study, we used three-dimensional （3D） collagen scaffolds as rat MSCs cartier and compared the properties of MSCs on 3D collagen scaffolds with monolayer cultured MSCs. The results demonstrated that collagen scaffolds were suitable for rat MSCs adherence and proliferation. More importantly, compared to MSCs under 2D culture, 3D MSCs significantly maintained higher expression levels of stemness genes （Oct4, Sox2, Rex-1 and Nanog）, yielded high frequencies of colony-forming units-fibroblastic （CFU-F） and showed enhanced osteogenic and adipogenic differentiation efficiency upon induction. Thus, 3D collagen scaffolds may be beneficial for expanding rat MSCs while maintaining the stem cell properties in vitro.

关键词： Three-dimensional culture Mesenchymal stem ceils Collagen scaffold Stemness