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Autologous bone marrow stem cell transplantation for the treatment of ulcerative colitis complicated

null

《医学前沿（英文）》 2016年第10卷第4期页码 522-526 doi: 10.1007/s11684-016-0485-4

摘要：

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with continuous or recurrent symptoms. A 42-year-old male patient with intermittent diarrhea accompanied by bloody mucopurulent stools was admitted to our hospital. The diagnosis of UC was confirmed by a combination of laboratory examination, colonoscopy, and histological assay. The patient developed herpes zoster in the hospital, which challenged traditional treatments. Therefore, we performed an autologous bone marrow cells to modulate the immune system with his permission. Autologous bone marrow mononuclear cells were collected and injected locally into the bowel mucosa, and subsequently injected systemically through a peripheral vein. After the patient underwent auto bone marrow mononuclear cells transplantations twice, the patient’s symptoms were alleviated. Furthermore, he recovered from hematochezia, and his hypersensitive C reactive protein decreased. Colonoscopy results showed reduced lesions and decreased areas with bleeding and edema in the sigmoid colon and rectum. No recurrence occurred in the subsequent two years, but long-time monitoring is still necessary for the prophylaxis of colorectal cancer.

关键词： autograft bone marrow stem cells ulcerative colitis cell therapy

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Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow

FANG Baijun, SONG Yongping, LIN Quande, ZHAO Chunhua, SHI Mingxia

《医学前沿（英文）》 2007年第1卷第2期页码 185-191 doi: 10.1007/s11684-007-0035-1

摘要： Previously, we reported that a cell population derived from human fetal bone marrow (BM), termed here Flk1CD34 postembryonic pluripotent stem cells (PPSCs) that have the characteristics of mesenchymal stem cells (MSCs), could differentiate into ectodermal, endodermal and mesodermal cell types at the single cell level , and that these cells could also differentiate into the epithelium of liver, lung, gut, as well as the hematopoietic and endothelial lineages after transplantion into irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In this study, we further isolated pluripotent stem cells from human fetal heart, liver, muscle, lung, derma, kidney, and fat and then analyzed the characteristics and function of these stem cells. It was found that the phenotype of the culture-expanded pluripotent stem cells from different fetal tissues was similar to BM-derived Flk1CD34 PPSCs, i.e. Flk1 and CD44 positive, GlyA, CD34, CD45, class I-HLA and HLA-DR negative. Morphologically, these cells were fibroblast-like and the doubling time was about 30 h. More importantly, culture-expanded pluripotent stem cells from all these fetal tissues were able to differentiate into cells with morphologic and phenotypic characteristics of adipocytes, osteocytes, neurons, glial cells and hepatocytes. These pluripotent stem cells with characteristics similar to fetal BM-derived Flk1CD34 PPSCs can be selected and cultured from tissues other than the BM. This phenomenon may help explain the stem cell plasticity found in multiple human tissues. In addition, as fetal BM-derived Flk1CD34 PPSCs, these pluripotent stem cells from different fetal tissues had the capacity for self-renewal and multi-lineage differentiation even after being expanded for more than 40 population doublings . Thus, they may be an ideal source of stem cells for treatment of inherited or degenerative diseases.

关键词： endothelial phenomenon ectodermal Flk1CD34 postembryonic irradiated non-obese

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自体骨髓干细胞移植研究进展

李连达,吴理茂,刘红,宁可永,李贻奎

《中国工程科学》 2004年第6卷第8期页码 1-4

摘要：

细胞移植作为一种新的治疗方法备受医学界关注，但细胞供应短缺和免疫排斥是阻碍这一疗法临床推广的主要难题。自体骨髓干细胞移植在一定程度上可缓解此矛盾。文章综述了自体骨髓干细胞移植治疗脑、肝、心等重要器官疾病的基础和临床研究现状，以及骨髓动员剂在骨髓干细胞移植中的作用。

关键词：骨髓干细胞自体移植骨髓动员剂

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大鼠骨髓间质干细胞的分离纯化与鉴定

张荣利,冯　雪,张会亮,罗国安,李连达,王义明

《中国工程科学》 2007年第9卷第7期页码 89-94

摘要：

采用密度梯度离心法分离骨髓间质干细胞，差速贴壁法进行纯化，应用流式细胞仪、激光共聚焦显微镜等对纯化细胞进行鉴定，结果细胞表面抗原CD29，CD44，CD105，CD166表达呈阳性，而CD14，CD34，CD45表达呈阴性。采用RT唱PCR鉴定了三个基因：nestin，NST，Oct-４，前两者呈阳性表达，后者弱阳性表达。这些细胞特异抗原与基因表达综合起来，表明得到的细胞具备骨髓间质干细胞的特性。密度梯度分离与差速贴壁相结合，可获得较好均一性的骨髓间质干细胞，是一种简单可靠、易于推广的骨髓干细胞获取方法，可为细胞与组织工程研究提供种子细胞。

关键词：大鼠骨髓间质干细胞流式细胞分析

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自体骨髓干细胞移植与归元方联用治疗急慢性肝损伤实验研究

吴理茂,李连达,刘红,宁可永,李贻奎

《中国工程科学》 2004年第6卷第7期页码 34-42

摘要：

研究中药归元方与自体骨髓干细胞移植对急慢性肝损伤的治疗作用。研究方法：用肝脏局部注射乙醇的方法复制急性局限性肝损伤模型，复合因素（CCl₄、乙醇、高脂、低蛋白）刺激复制大鼠肝纤维化模型，通过定量组织学、肝功能检查、免疫组化、肝组织羟脯氨酸含量、损伤或纤维区骨髓干细胞观察等综合评价中药、自体骨髓干细胞移植及两者合用的疗效。结果：归元方与自体骨髓干细胞移植可减小肝损伤区域，改善肝功能，使纤维肝组织表达μPA增强，降低血清ALT，AST，PCⅢ，HA和肝组织羟脯氨酸的含量，改善肝组织肝纤维化评分，骨髓干细胞能在肝损伤、肝纤维化形成环境中存活、增殖，并向肝细胞分化，表达肝脏特异的角蛋白CK18。结论：归元方与自体骨髓干细胞移植对急慢性肝损伤有明确的治疗作用，两者合用可优势互补，协同增效。临床上有良好的应用前景。

关键词：归元方骨髓干细胞自体移植肝损伤肝纤维化

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FGF13 suppresses acute myeloid leukemia by regulating bone marrow niches

《医学前沿（英文）》 2022年第16卷第6期页码 896-908 doi: 10.1007/s11684-022-0944-z

摘要： Fibroblast growth factor 13 (FGF13) is aberrantly expressed in multiple cancer types, suggesting its essential role in tumorigenesis. Hence, we aimed to explore its definite role in the development of acute myeloid leukemia (AML) and emphasize its associations with bone marrow niches. Results showed that FGF13 was lowly expressed in patients with AML and that its elevated expression was related to prolonged overall survival (OS). Univariate and multivariate Cox regression analyses identified FGF13 as an independent prognostic factor. A prognostic nomogram integrating FGF13 and clinicopathologic variables was constructed to predict 1-, 3-, and 5-year OS. Gene mutation and functional analyses indicated that FGF13 was not associated with AML driver mutations but was related to bone marrow niches. As for immunity, FGF13 was remarkably associated with T cell count, immune checkpoint genes, and cytokines. In addition, FGF13 overexpression substantially inhibited the growth and significantly induced the early apoptosis of AML cells. The xenograft study indicated that FGF13 overexpression prolonged the survival of recipient mice. Overall, FGF13 could serve as an independent prognostic factor for AML, and it was closely related to the bone marrow microenvironment.

关键词： acute myeloid leukemia FGF13 prognosis immune-related genes bone marrow niches

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the intensity and loading time of direct current electric field on the directional migration of rat bonemarrow mesenchymal stem cells

null

《医学前沿（英文）》 2016年第10卷第3期页码 286-296 doi: 10.1007/s11684-016-0456-9

摘要：

Exogenic electric fields can effectively accelerate bone healing and remodeling through the enhanced migration of bone marrow mesenchymal stem cells (BMSCs) toward the injured area. This study aimed to determine the following: (1) the direction of rat BMSC (rBMSC) migration upon exposure to a direct current electric field (DCEF), (2) the optimal DCEF intensity and duration, and (3) the possible regulatory role of SDF-1/CXCR4 axis in rBMSC migration as induced by DCEF. Results showed that rBMSCs migrated to the positive electrode of the DCEF, and that the DCEF of 200 mV/mm for 4 h was found to be optimal in enhancing rBMSC migration. This DCEF strength and duration also upregulated the expression of osteoblastic genes, including ALP and OCN, and upregulated the expression of ALP and Runx2 proteins. Moreover, when CXCR4 was inhibited, rBMSC migration due to DCEF was partially blocked. These findings indicated that DCEF can effectively induce rBMSC migration. A DCEF of 200 mV/mm for 4 h was recommended because of its ability to promote rBMSC migration, proliferation, and osteogenic differentiation. The SDF-1/CXCR4 signaling pathway may play an important role in regulating the DCEF-induced migration of rBMSCs.

关键词： DCEF migration osteogenesis differentiation rBMSCs SDF-1/CXCR-4

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Outcomes of haploidentical bone marrow transplantation in patients with severe aplastic anemia-II that

《医学前沿（英文）》 2021年第15卷第5期页码 718-727 doi: 10.1007/s11684-020-0807-4

摘要： Severe aplastic anemia II (SAA-II) progresses from non-severe aplastic anemia (NSAA). The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation (haplo-BMT) in patients lacking a human leukocyte antigen (HLA)-matched donor. This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II. Twenty-two patients were included and followed up, and FLU/BU/CY/ATG was used as conditioning regimen. Among these patients, 21 were successfully engrafted, 19 of whom survived after haplo-BMT. Four patients experienced grade II–IV aGvHD, including two with grade III–IV aGvHD. Six patients experienced chronic GvHD, among whom four were mild and two were moderate. Twelve patients experienced infections during BMT. One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease, and both recovered after rituximab infusion. Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4%±0.73% after a median follow-up of 42 months, indicating its effectiveness as a salvage therapy. These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.

关键词： severe aplastic anemia non-severe acquired aplastic anemia haploidentical bone marrow transplantation outcomes

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Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region

Zhiyuan Zhang

《医学前沿（英文）》 2011年第5卷第4期页码 401-413 doi: 10.1007/s11684-011-0161-7

摘要： Clinical imperatives for the reconstruction of jaw bone defects or resorbed alveolar ridge require new therapies or procedures instead of autologous/allogeneic bone grafts. Regenerative medicine, based on stem cell science and tissue engineering technology, is considered as an ideal alternative strategy for bone regeneration. In this paper, we review the current choices of cell source and strategies on directing the osteogenic differentiation of stem cells. The preclinical animal models for bone regeneration and the key translational points to clinical success in oral and maxillofacial region are also discussed. We propose comprehensive strategies based on stem cell and tissue engineering researches, allowing for clinical application in oral and maxillofacial region.

关键词： bone regeneration animal models translational strategies oral and maxillofacial region

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Determination of telomerase activity in stem cells and non-stem cells of breast cancer

LI Zhi, HE Yanli, ZHANG Jiahua, ZHANG Jinghui, HUANG Tao

《医学前沿（英文）》 2007年第1卷第3期页码 294-298 doi: 10.1007/s11684-007-0056-9

摘要： Although all normal tissue cells, including stem cells, are genetically homologous, variation in gene expression patterns has already determined the distinct roles for individual cells in the physiological process due to the occurrence of epigenetic modification. This is of special importance for the existence of tissue stem cells because they are exclusively immortal within the body, capable of selfreplicating and differentiating by which tissues renew and repair itself and the total tissue cell population maintains a steady-state. Impairment of tissue stem cells is usually accompanied by a reduction in cell number, slows down the repair process and causes hypofunction. For instance, chemotherapy usually leads to depression of bone marrow and hair loss. Cellular aging is closely associated with the continuous erosion of the telomere while activation of telomerase repairs and maintains telomeres, thus slowing the aging process and prolonging cell life. In normal adults, telomerase activation mainly presents in tissue stem cells and progenitor cells giving them unlimited growth potential. Despite the extensive demonstration of telomerase activation in malignancy (>80%), scientists found that heterogeneity also exists among the tumor cells and only minorities of cells, designated as cancer stem cells, undergo processes analogous to the self-renewal and differentiation of normal stem cells while the rest have limited lifespans. In this study, telomerase activity was measured and compared in breast cancer stem cells and non-stem cells that were phenotypically sorted by examining surface marker expression. The results indicated that cancer stem cells show a higher level of enzyme activity than non-stem cells. In addition, associated with the repair of cancer tissue (or relapse) after chemotherapy, telomerase activity in stem cells was markedly increased.

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Porcine pluripotent stem cells: progress, challenges and prospects

Jianyong HAN, Yi-Liang MIAO, Jinlian HUA, Yan LI, Xue ZHANG, Jilong ZHOU, Na LI, Ying ZHANG, Jinying ZHANG, Zhonghua LIU

《农业科学与工程前沿（英文）》 2019年第6卷第1期页码 8-27 doi: 10.15302/J-FASE-2018233

摘要：

Pluripotent stem cells (PSCs) are characterized by their capacity for high self-renewal and multiple differentiation potential and include embryonic stem cells, embryonic germ cells and induced PSCs. PSCs provide a very suitable model for the studies of human diseases, drugs screening, regenerative medicine and developmental biology research. Pigs are considered as an ideal model for preclinical development of human xenotransplantation, therapeutic approaches and regenerative medicine because of their size and physiological similarity to humans. However, lack of knowledge about the derivation, characterization and pluripotency mechanisms of porcine PSCs hinders progress in these biotechnologies. In this review, we discuss the latest progress on porcine PSCs generation, evaluation criteria for pluripotency, the scientific and technical questions arising from these studies. We also introduce our perspectives on porcine PSC research, in the hope of providing new ideas for generating naive porcine PSCs and animal breeding.

关键词： embryonic germ cells embryonic stem cells induced pluripotent stem cells pigs pluripotent stem cells

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The past, present and future of bovine pluripotent stem cells: a brief overview

Xiuchun TIAN

《农业科学与工程前沿（英文）》 2019年第6卷第1期页码 3-7 doi: 10.15302/J-FASE-2018247

摘要：

Although the pursuit of bovine embryonic stem cells started more than 26 years ago for the purpose of gene-targeting, true pluripotent stem cells in this economically important species are still elusive. With the rapid advances in genome-editing and cloning using homologously recombined somatic cells, the need for pluripotent stem cells for precise genetic modification in any species became questionable. With the pig being the better model for human regenerative biology, the identification of the commonalities and uniqueness of the pluripotency circuitry across mammalian species may be the main objective for studying pluripotent stem cells in the bovine.

关键词： bovine embryonic induced pluripotent stem cells

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Umbilical cord-derived mesenchymal stem cells: strategies, challenges, and potential for cutaneous regeneration

null

《医学前沿（英文）》 2012年第6卷第1期页码 41-47 doi: 10.1007/s11684-012-0175-9

摘要：

Umbilical cord mesenchymal stem cells (MSCs) are a unique, accessible, and non-controversial source of early stem cells that can be readily manipulated. As the most common pluripotent cell, bone marrow-derived MSCs display limitations with the progress of stem cell therapy. By contrast, umbilical cord-derived cells, which have plentiful resources, are more accessible. However, several uncertain aspects, such as the effect of donor selection or culture conditions, long-term therapeutic effects, product consistency, and potential tumorigenicity, are the bottleneck in this clinical therapy. MSCs are predicted to undergo an unprecedented development in clinical treatment when a generally acknowledged criterion emerges. In the current paper, we highlight the application of umbilical cord-derived MSCs in skin therapies based on our previous studies, as well as the achievements of our peers in this field. This paper focuses on the strategies, challenges, and potential of this novel therapy.

关键词： umbilical cord mesenchymal stem cells cutaneous regeneration

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Current advances for bone regeneration based on tissue engineering strategies

Rui Shi, Yuelong Huang, Chi Ma, Chengai Wu, Wei Tian

《医学前沿（英文）》 2019年第13卷第2期页码 160-188 doi: 10.1007/s11684-018-0629-9

摘要： Bone tissue engineering (BTE) is a rapidly developing strategy for repairing critical-sized bone defects to address the unmet need for bone augmentation and skeletal repair. Effective therapies for bone regeneration primarily require the coordinated combination of innovative scaffolds, seed cells, and biological factors. However, current techniques in bone tissue engineering have not yet reached valid translation into clinical applications because of several limitations, such as weaker osteogenic differentiation, inadequate vascularization of scaffolds, and inefficient growth factor delivery. Therefore, further standardized protocols and innovative measures are required to overcome these shortcomings and facilitate the clinical application of these techniques to enhance bone regeneration. Given the deficiency of comprehensive studies in the development in BTE, our review systematically introduces the new types of biomimetic and bifunctional scaffolds. We describe the cell sources, biology of seed cells, growth factors, vascular development, and the interactions of relevant molecules. Furthermore, we discuss the challenges and perspectives that may propel the direction of future clinical delivery in bone regeneration.

关键词： bone tissue engineering stem cell bone scaffold growth factor bone regeneration

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Mesenchymal stem cells hold promise for regenerative medicine

Shihua Wang, Xuebin Qu, Robert Chunhua Zhao

《医学前沿（英文）》 2011年第5卷第4期页码 372-378 doi: 10.1007/s11684-011-0164-4

摘要： Regenerative medicine is an emerging interdisciplinary field of research that uses several technological approaches including stem cells to repair tissues. Mesenchymal stem cells (MSCs), a type of adult stem cell, have generated a great amount of interest over the past decade in this field. Numerous studies have explored the role of MSCs in tissue repair and modulation of allogeneic immune responses. The mechanisms through which MSCs exert their therapeutic potential rely on some key properties of the cells as follows: the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial, and neuronal cells; the ability to secrete multiple bioactive molecules capable of stimulating the recovery of injured cells and inhibiting inflammation; the lack of immunogenicity; and the ability to perform immunomodulatory functions. In the present review, we focus on these three aspects upon which the therapeutic effects of MSCs are mainly based. Furthermore, some pathological conditions under which the application of MSCs should be done with caution are also mentioned.

关键词： mesenchymal stem cells differentiation immunomodulation regenerative medicine