文献类型：期刊文献

英文题名：A modular approach to the engineering of a centimeter-sized bone tissue construct with human amniotic mesenchymal stem cells-laden microcarriers

作者：Chen, Maiqin[1];Wang, Xiu[1];Ye, Zhaoyang[1];Zhang, Yan[2];Zhou, Yan[1];Tan, Wen-Song[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Sch Bioengn, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Sch Mat Sci & Engn, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China

年份：2011

卷号：32

期号：30

起止页码：7532

外文期刊名：BIOMATERIALS

收录：;EI(收录号：20113314233659);WOS:【SCI-EXPANDED(收录号:WOS:000294829300024)】；

基金：Financial supports from the Fundamental Research Funds for the Central Universities, the National Special Fund for State Key Laboratory of Bioreactor Engineering (2060204), Shanghai Natural Science Foundation (10ZR1407100), Shanghai Pujiang Program (10PJ1402200), Doctoral Program Foundation of Institutions of Higher Education of China (20100074120009) and National Natural Science Foundation of China (20776044, 31000424) were gratefully acknowledged.

语种：英文

外文关键词：Tissue engineering; Modular approach; Microcarriers; Macrotissue; Mesenchymal stem cells; Osteogenic differentiation

摘要：Tissue engineering of clinical-relevant large tissue constructs remains a big challenge due to the mass transfer limit. A modular approach via the assembling of modular tissues thus eliminating the mass transfer limit holds great promise for fabricating centimeter-sized constructs. In the present study, we investigated the feasibility of using microcarriers seeded with adult mesenchymal stem cells (MSCs) to fabricate a large bone tissue. It was demonstrated that human amniotic MSCs (hAMSCs) were efficiently seeded onto CultiSpher S microcarriers (made of porcine gelatin) in a spinner flask and quickly proliferated while retaining a great viability. Within a total culture period of 28 days, using a two-stage culture strategy, hAMSCs-laden microcarriers with a high cell density were prepared at the first stage and the cells were then directly induced to undergo osteogenic differentiation in the same culture flask. During this cultivation process, the aggregation of cell-laden microcarriers was apparent, which resulted in aggregates of 700-800 mu m, a size permissive for maintaining high cell viability. The osteogenic differentiation of hAMSCs on microcarriers was confirmed with increased mineral deposition (Alizarin red S staining and quantification of calcium content), ALP activity as well as gene expression of osteogenic markers (collagen type I and osteocalcin). These modular bone-like tissues were used as building blocks to fabricate a macroscopic bone construct in a cylindrical perfusion culture chamber (2 cm in diameter). After a 7-day perfusion culture, these modular tissues readily assembled into a centimeter-sized construct (diameter x height: 2 cm x 1 cm). Both good cell viability and fairly homogenous distribution of cellular content and bone-characteristic ECM within the macrotissue were elaborated. This paper provided a proof-of-concept study for modularly engineering clinical-relevant large tissue replacements with cell-laden microcarriers. (C) 2011 Elsevier Ltd. All rights reserved.