崔磊
组织工程骨的探索性临床应用研究
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- 姓名:崔磊
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外科学
- 研究兴趣:组织工程骨的探索性临床应用研究
崔磊,男,1968年8月出生,无党派,汉族,博士,副教授,博士生导师,上海交通大学医学院附属第九人民医院组织工程研究中心副主任,上海组织工程研究与开发中心副主任,组织工程国家工程研究中心常务副主任,上海国睿生命科技有限公司执行总裁。 崔磊同志是一名具有强烈责任心与敬业精神、创新开拓的复合型科技与管理人才。
围绕组织工程的临床实际应用为主要方向,在国际上率先开展了组织工程骨的探索性临床应用研究并取得了较好的临床治疗效果,为骨缺损病人的治疗开辟了崭新的途径,研究成果标志着中国组织工程研究在组织构建领域已经处于国际领先水平。研究并攻克了骨组织工程产品开发与产业发展的诸多关键技术问题,负责起草我国第一份骨组织工程产品的企业标准,建立了与国际接轨的产品质量控制体系,研究与应用成果推动了国家组织工程产业化的发展。在血管、角膜、软骨等组织工程领域及相关的干细胞、生物材料等方向上也取得多项创新性研究成果,发表文章20余篇(其中以第一作者、通讯作者在国际组织工程领域权威刊物发表文章5篇,总影响因子20),申报国家发明专利多项。在承担繁重科研任务的同时,通过主持国家组织工程工程中心(上海国睿生命科技有限公司)的日常管理工作,积极探索并建立了有效的产学研一体、多单位及多学科交叉与合作的科学管理体系,其不计较得失的合作精神赢得了合作伙伴的普遍认同,带动了上海组织工程研究的整体发展。主持并负责上海市科教兴市重大项目、上海市重大建设工程-组织工程国家工程研究中心的建设与日常管理工作,在较短的时间内,优质、高效地完成了国家工程中心的建筑任务。建设项目获上海市文明工地、上海市优质结构工程等称号。项目的建成将大大推动我国组织工程研究的产业化发展、提升我国组织工程研究的国际学术形象。
作为负责人荣获上海医学科技二等奖一项,作为主要完成人荣获上海科技进步一等奖2项、上海科技进步二等奖、中华医学科技二等奖、上海医学科技奖二等奖、中华医学科技奖三等奖、中国高校科技二等奖等多项奖励。
被授予全国“973”先进个人、全国优秀青年骨干教师、霍英东青年教师奖、上海市教委“曙光学者”、上海市科委“启明星”、“启明星后”等多项荣誉称号。
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崔磊, Xiaogang
Journal of proteome Research 2007, 6, 2287-2294,-0001,():
-1年11月30日
Exploring
protein
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崔磊, LEI
TISSUE ENGINEERING Volume 13, Numbei 6, 2007,-0001,():
-1年11月30日
Multipotent mesenchymal stem cells (MSCs) in adult tissue are known to be less immunogenic and immunosuppressive. Previous study showed that primary cultures of human adipose-derived stem cells (ADSCs) shared their immunomodulatory properties with other MSCs. However, whether passaged human ADSCs can retain their immunomodulatory effect after in vitro expansion remains unknown. In addition, the mechanism of ADSC-mediated immunomodulatory effect remains to be elucidated. This study aimed to investigate these issues by using passaged human ADSCs as an in vitro study model. Flow cytometry showed that passaged ADSCs expressed human leukocyte antigen (HLA) class I but not class II molecules, which could be induced to express to a high level with interferon-c (IFN-c) treatment. The study found that passaged ADSCs could not elicit lymphocyte proliferation after co-culturing with them, even after IFN-c treatment. In addition, either IFN-c–treated or non-treated ADSCs could inhibit phytohemagglutinin (PHA)-stimulated lymphocyte proliferation.Moreover, passaged ADSCs could serve as the third-party cells to inhibited two-waymixed lymphocyte reaction (MLR). Further study using a transwell system also showed that this type of immunosuppressive effect was not cell–cell contact dependent. In defining possible soluble factors, we found that passaged ADSCs significantly increased their secretion of prostaglandin E2 (PGE2), but not transforming growth factor-b (TGF-β) and hepatocyte growth factor (HGF), when theywere co-cultured with MLR. Furthermore, the result demonstrated that only PGE2 production inhibitor indomethacine, but not TGF-β- and HGF-neutralizing antibodies, could significantly counteract ADSCmediated suppression on allogeneic lymphocyte proliferation. These results indicated that in vitro expanded ADSCs retain low immunogenicity and immunosuppressive effect, and PGE2 might be the major soluble factor involved in the in vitro inhibition of allogeneic lymphocyte reaction.
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崔磊, Jie
Biomaterials 28(2007)1005-1013,-0001,():
-1年11月30日
Tissue engineering has become a new approach for repairing bone defects. Previous studies have been limited to the use of slowdegradable scaffolds with bone marrow stromal cells (BMSCs) in mandibular reconstruction. In this study, a 30mm long mandibular segmental defect was repaired by engineered bone graft using osteogenically induced autologouse BMSCs seeded on porous β-tricalcium phosphate (β-TCP, n=5). The repair of defects was compared with those treated with β-TCP alone (n=6) or with autologous mandibular segment (n=4). In the BMSCs/b-TCP group, new bone formation was observed from 4 weeks post-operation, and bonyunion was achieved after 32 weeks, which was detected by radiographic and histological examination. In contrast, minimal bone formation with almost fibrous connection was observed in the group treated with β-TCP alone. More importantly, the engineered bone with BMSCs/β-TCP achieved a satisfactory biomechanical property in terms of bending load strength, bending displacement, bending stress and Young's modulus at 32 weeks post-operation, which was very close to those of contralateral edentulous mandible and autograft bone (p>0.05). Based on these results, we conclude that engineered bone from osteogenically induced BMSCs and biodegradable β-TCP can well repair the critical-sized segmental mandibular defects in canines.
Tissue engineering, Bone marrow stromal cells, β-tricalcium phosphate, Mandibular reconstruction
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崔磊, XIAOJIE
TISSUE ENGINEERING Volume 11, Numbei 11/12, 2005,-0001,():
-1年11月30日
We determined whether a polyglycolic acid (PGA) scaffold bearing an adherent corneal stromal cell insert could be integrated into the ultrastructure of rabbit corneal stroma without compromising tissue transparency. Stromal cells were isolated from 10 newborn rabbits and expanded by tissue culture. After reaching confluence, the cells were harvested and mixed with nonwoven PGA fibers to form cell–scaffold constructs. After 1 week of culturing, they were implanted into the corneal stroma of female rabbit recipients. Green fluorescent protein (GFP) expression in transplanted corneal stromal cells was monitored at the protein level to determine cellular origin in the reconstructed stroma. Eight weeks after implantation, transmission electron microscopy and histological evaluation were performed on stromal tissue. Insertion of PGA scaffold alone served as a sham control. After stromal implantation, implants gradually became transparent over an 8-week period. During this time stromal histology was gradually restored, as collagen fibril organization approached that of their normal counterpart. GFP-labeled corneal stromal cells were preponderant in the regions bearing inserted scaffolds, suggesting that they were derived from the implants rather than from neighboring corneal stromal cells. No reconstructed stroma developed in regions where naked PGA was implanted instead. We conclude that intrastromal implantation of PGA fiber scaffold implants bearing corneal stromal cells is a useful procedure for corneal stromal tissue reconstruction because, over an 8-week period, the implants become progressively more transparent. Marked losses of translucence during this period combined with restoration of ultrastructure indicate that the implants provide the functions needed for deturgescing initially swollen stroma.
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崔磊, Lei
Key Engineering Materials Vols. 288-289(2005)pp. 63-66,-0001,():
-1年11月30日
Objective
demineralized
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崔磊, DEJUN
TISSUE ENGINEERING Volume 12, Number 5, 2006,-0001,():
-1年11月30日
Although there are many reports of in vivo tendon engineering using different animal models, only a few studies involve the short-term investigation of in vitro tendon engineering. Our previous study demonstrated that functional tendon tissue could be engineered in vivo in a hen model using tenocytes and polyglycolic acid (PGA) fibers. This current study explored the feasibility of in vitro tendon engineering using the same type of cells and scaffold material. Tenocytes were extracted from the tendons of a hen’s foot with enzyme digestion and cultured in DMEM plus 10% FBS. Unwoven PGA fibers were arranged into a cord-like construct and fixed on a U-shape spring, and tenocytes were then seeded on PGA fibers to generate a cell-PGA construct. In experimental group 1, 22 cellscaffold constructs were fixed on the spring with no tension and collected at weeks 4 (n=7), 6 (n=7) and 10 (n=8); in experimental group 2, five cell-scaffold constructs were fixed on the spring with a constant strain and collected after 6 weeks of culture. In the control group, three cell-free scaffolds were fixed on the spring without tension. The collected engineered tendons were subjected to gross and histological examinations and biomechanical analysis. The results showed that tendon tissue could be generated during in vitro culture. In addition, the tissue structure and mechanical property became more mature and stronger with the increase of culture time. Furthermore, application of constant strain could enhance tissue maturation and improve mechanical property of the in vitro engineered tendon (1.302±0.404 Mpa with tension vs 0.406±0.030 Mpa without tension at 6 weeks). Nevertheless, tendon engineered with constant strain appeared much thinner in its diameter than tendon engineered without mechanical loading. Additionally, its collagen fibers were highly compacted when compared to natural tendon structure, suggesting that constant strain may not be the optimal means of mechanical load. Thus, application of dynamic mechanical load with a bioreactor to the construction of tendon tissue will be our next goal in this series of in vitro tendon engineering study.
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崔磊, WEI
TISSUE ENGINEERING Volume 12, Number 4, 2006,-0001,():
-1年11月30日
Harvesting autologous tenocytes for tendon engineering may cause secondary tendon defect at the donor site. Dermal fibroblasts are an easily accessible cell source and do not cause major donor site defect. This study aims to explore the possibility of tendon engineering using dermal fibroblasts. A total of 45 hybrid pigs were randomly divided into three groups: experimental group (n=15)–repair of tendon defect with a dermal fibroblast engineered tendon; control group 1 (n=15)–repair of defect with a tenocyte engineered tendon; and control group 2 (n=15)–repair of defect with a scaffold alone. Both autologous dermal fibroblasts and tenocytes were seeded on polyglycolic acid (PGA) unwoven fibers to form a cell-scaffold construct and cultured in vitro for 7 days before in vivo implantation to repair a defect of flexor digital superficial tendon. Specimens were harvested at weeks 6, 14, and 26 for gross, histological, and mechanical analyses. Microscopy revealed good attachment of both dermal fibroblasts and tenocytes on PGA fibers and matrix production. In vivo results showed that fibroblast and tenocyte engineered tendons were similar to each other in their gross view, histology, and tensile strength. At 6 weeks, parallel collagen alignment was observed at both ends, but not in the middle in histology, with more cellular components than natural tendons. At weeks 14 and 26, both engineered tendons exhibited histology similar to that of natural tendon. Collagens became parallel throughout the tendon structure, and PGA fibers were completely degraded. Interestingly, dermal fibroblast and tenocyte engineered tendons did not express type III collagen at 26 weeks, which remained observable in normal pig skin and control group 2 tissue using polarized microscopy, suggesting a possible phenotype change of implanted dermal fibroblasts. Furthermore, both fibroblast and tenocyte engineered tendons shared similar tensile strength, about 75% of natural tendon strength. At 6 weeks in control group 2, neo-tissue was formed only at the peripheral area by host cells. A cord-like tissue was formed at weeks 14 and 26. However, the formed tissue was histologically disorganized and mechanically weaker than both cell-engineered tendons (p<0.05). These results suggest that dermal fibroblasts may have the potential as seed cells for tendon engineering.
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崔磊, YULAI WENG, M.D., Ph.D., , † MIN WANG, † WEI LIU, XIAOJIE HU, GANG CHAI, QIAOMEI YAN, LIAN ZHU, LEI CUI, and YILIN CAO
TISSUE ENGINEERING Volume 12, Number 6, 2006,-0001,():
-1年11月30日
Alveolar bone resorption caused by periodontal diseases remains a difficult clinical problem to treat. Our purpose here was to develop protocols for repairing experimental horizontal alveolar bone defects. The procedure entailed isolating bone marrow stromal cells (BMSC). They were expanded and induced in vitro into osteogenic cells in a defined medium. Induced BMSCs were mixed with calcium alginate to form a gel form of cell–scaffold construct for developing engineered bone. A horizontal alveolar bone defect was created in 15 mongrel dogs, which was 5 mm high on each of two buccal sides at the location of mandibular premolar 3, 4, and molar 1. Without bias, the animals were separated into the following groups: (1) cell–scaffold construct as the experimental group; (2) calcium alginate alone as the control group A; (3) untreated as the control group B. Block sections of the defects were collected at 4, 12, and 24 weeks postsurgery, respectively, and processed for gross and histological observation as well as x-ray examination. The results showed that in vitro induced BMSCs exhibited an osteogenic phenotype. Histologically, bone nodule structure was observed in the tissue of the experimental group at 4 weeks postsurgery and the engineered bone became more mature after 12 weeks, which was similar to normal bone. At 12 weeks postsurgery, the height of repaired alveolar bone reached 2.43±0.93 mm, 0.98±0.87 mm, 0.78±0.75 mm for the experimental group, control groups A and B, respectively, with a significant difference between the experimental and control groups (p<0.01). The average level of buccal alveolar ridge in experimental group, control groups A and B reached 48.59%, 19.74%, and 15.76% of the height of normal alveolus, respectively, with a significant difference between the experimental group and two control groups (p<0.01). We thus conclude that BMSCs can be induced to become osteogenic and can be used as seed cells to engineer bone tissue and repair experimental alveolar bone defects.
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崔磊, LIAN
TISSUE ENGINEERING Volume 12, Number 3, 2006,-0001,():
-1年11月30日
Tissue
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