Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can acti...Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3 a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.展开更多
Bone is the second most commonly transplanted tissue worldwide,with over four million operations using bone grafts or bone substitute materials annually to treat bone defects.However,significant limitations affect cur...Bone is the second most commonly transplanted tissue worldwide,with over four million operations using bone grafts or bone substitute materials annually to treat bone defects.However,significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma,cancer,infection and arthritis.Developing bioactive three-dimensional(3D)scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering(BTE).A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts.However,individual groups of materials including polymers,ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone.Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds.This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers,hydrogels,metals,ceramics and bio-glasses in BTE.Scaffold fabrication methodology,mechanical performance,biocompatibility,bioactivity,and potential clinical translations will be discussed.展开更多
The WD40 domain exhibits aβ-propeller architecture,often comprising seven blades.The WD40 domain is one of the most abundant domains and also among the top interacting domains in eukaryotic genomes.In this review,we ...The WD40 domain exhibits aβ-propeller architecture,often comprising seven blades.The WD40 domain is one of the most abundant domains and also among the top interacting domains in eukaryotic genomes.In this review,we will discuss the identification,definition and architecture of the WD40 domains.WD40 domain proteins are involved in a large variety of cellular processes,in which WD40 domains function as a protein-protein or protein-DNA interaction platform.WD40 domain mediates molecular recognition events mainly through the smaller top surface,but also through the bottom surface and sides.So far,no WD40 domain has been found to display enzymatic activity.We will also discuss the different binding modes exhibited by the large versatile family of WD40 domain proteins.In the last part of this review,we will discuss how post-translational modifications are recognized by WD40 domain proteins.展开更多
Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the...Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells(BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.展开更多
Tissue engineering is promising in realizing successful treatments of human body tissue loss that current methods cannot treat well or achieve satisfactory clinical outcomes.In scaffold-based bone tissue engineering,a...Tissue engineering is promising in realizing successful treatments of human body tissue loss that current methods cannot treat well or achieve satisfactory clinical outcomes.In scaffold-based bone tissue engineering,a high performance scaffold underpins the success of a bone tissue engineering strategy and a major direction in the field is to produce bone tissue engineering scaffolds with desirable shape,structural,physical,chemical and biological features for enhanced biological performance and for regenerating complex bone tissues.Three-dimensional(3D)printing can produce customized scaffolds that are highly desirable for bone tissue engineering.The enormous interest in 3D printing and 3D printed objects by the science,engineering and medical communities has led to various developments of the 3D printing technology and wide investigations of 3D printed products in many industries,including biomedical engineering,over the past decade.It is now possible to create novel bone tissue engineering scaffolds with customized shape,architecture,favorable macro-micro structure,wettability,mechanical strength and cellular responses.This article provides a concise review of recent advances in the R&D of 3D printing of bone tissue engineering scaffolds.It also presents our philosophy and research in the designing and fabrication of bone tissue engineering scaffolds through 3D printing.展开更多
Damaged articular cartilage has very limited capacity for spontaneous healing. Tissue engineering provides a new hope for functional cartilage repair. Creation of an appropriate cell carrier is one of the critical ste...Damaged articular cartilage has very limited capacity for spontaneous healing. Tissue engineering provides a new hope for functional cartilage repair. Creation of an appropriate cell carrier is one of the critical steps for successful tissue engineering. With the supposition that a biomimetic construct might promise to generate better effects, we developed a novel composite scaffold and investigated its potential for cartilage tissue engineering.展开更多
基金supported by Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01030501 to Haixiang Sun)National Natural Science Foundation of China (31571189, 81571391, 30900847 to Lijun Ding)+1 种基金Jiangsu Provincial Medical Youth Talent (QNRC2016006)Nanjing Medical Science Development Project (JQX14004, ZKX16042)
文摘Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3 a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.
文摘Bone is the second most commonly transplanted tissue worldwide,with over four million operations using bone grafts or bone substitute materials annually to treat bone defects.However,significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma,cancer,infection and arthritis.Developing bioactive three-dimensional(3D)scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering(BTE).A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts.However,individual groups of materials including polymers,ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone.Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds.This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers,hydrogels,metals,ceramics and bio-glasses in BTE.Scaffold fabrication methodology,mechanical performance,biocompatibility,bioactivity,and potential clinical translations will be discussed.
基金This research was supported by the Structural Genomics Consortium,a registered charity(No.1097737)that receives funds fromthe Canadian Institutes for Health Research,the Canadian Foundation for Innovation,Genome Canada through the Ontario GenomicsInstitute,Glaxo Smith Kline,Karolinska Institutet,the Knut and Alice Wallenberg Foundation,the Ontario lnnovation Trust,the Ontario Ministry for Research and Innovation,Merck&Co.,Inc.,the Novartis Research Foundation,the Swedish Agency for Innovation Systems,the Swedish Foundation for Strategic Research and the Wellcome Trust.
文摘The WD40 domain exhibits aβ-propeller architecture,often comprising seven blades.The WD40 domain is one of the most abundant domains and also among the top interacting domains in eukaryotic genomes.In this review,we will discuss the identification,definition and architecture of the WD40 domains.WD40 domain proteins are involved in a large variety of cellular processes,in which WD40 domains function as a protein-protein or protein-DNA interaction platform.WD40 domain mediates molecular recognition events mainly through the smaller top surface,but also through the bottom surface and sides.So far,no WD40 domain has been found to display enzymatic activity.We will also discuss the different binding modes exhibited by the large versatile family of WD40 domain proteins.In the last part of this review,we will discuss how post-translational modifications are recognized by WD40 domain proteins.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01030505)Key research and development program of Jiangsu province (BE2016612), Jiangsu Biobank of Clinical Resources (BM2015004)+1 种基金the Key Laboratory for Maternal-Fetal Medicine from the Health Department of Jiangsu Province, China (XK201102)Project of Nanjing clinical medicine center and the National Natural Science Foundation of China (81401223)
文摘Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells(BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.
基金This work was supported by Dongguan University of Technology High-level Talents(Innovation Team)Research Project(KCYCXPT201603)Youth Innovative Talent Project from the Department of Education of Guangdong Province,China(2016KQNCX168)Natural Science Foundation of Guangdong Province,China(2018A0303130019).
文摘Tissue engineering is promising in realizing successful treatments of human body tissue loss that current methods cannot treat well or achieve satisfactory clinical outcomes.In scaffold-based bone tissue engineering,a high performance scaffold underpins the success of a bone tissue engineering strategy and a major direction in the field is to produce bone tissue engineering scaffolds with desirable shape,structural,physical,chemical and biological features for enhanced biological performance and for regenerating complex bone tissues.Three-dimensional(3D)printing can produce customized scaffolds that are highly desirable for bone tissue engineering.The enormous interest in 3D printing and 3D printed objects by the science,engineering and medical communities has led to various developments of the 3D printing technology and wide investigations of 3D printed products in many industries,including biomedical engineering,over the past decade.It is now possible to create novel bone tissue engineering scaffolds with customized shape,architecture,favorable macro-micro structure,wettability,mechanical strength and cellular responses.This article provides a concise review of recent advances in the R&D of 3D printing of bone tissue engineering scaffolds.It also presents our philosophy and research in the designing and fabrication of bone tissue engineering scaffolds through 3D printing.
基金This study was supported by a grant from Guangdong ProvincialScience &Technology Project, China (No. 2003A302102).
文摘Damaged articular cartilage has very limited capacity for spontaneous healing. Tissue engineering provides a new hope for functional cartilage repair. Creation of an appropriate cell carrier is one of the critical steps for successful tissue engineering. With the supposition that a biomimetic construct might promise to generate better effects, we developed a novel composite scaffold and investigated its potential for cartilage tissue engineering.