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新型多孔明胶-海藻酸钠支架对骨髓基质细胞的体外和体内差异反应。

The differential in vitro and in vivo responses of bone marrow stromal cells on novel porous gelatin-alginate scaffolds.

机构信息

Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada.

出版信息

J Tissue Eng Regen Med. 2009 Dec;3(8):601-14. doi: 10.1002/term.201.

DOI:10.1002/term.201
PMID:19685485
Abstract

Tissue engineering and stem cell therapy hold great potential of being able to fully restore, repair and replace damaged, diseased or lost tissues in the body. Biocompatible porous scaffolds are used for the delivery of cells to the regeneration sites. Marrow stromal cells (MSCs), also referred to as mesenchymal stem cells, are an attractive cell source for tissue engineering, due to the relative ease of isolation and the ability of in vitro expanded MSCs to generate multiple cell types, including osteoblasts, chondrocytes and adipocytes. This study utilized a novel technique called microwave vacuum drying to fabricate porous gelatin-alginate scaffolds for the delivery of MSCs and investigated the differential in vitro and in vivo responses of MSCs seeded on these scaffolds. Scaffold total porosity was found to decrease with increased cross-link density but the pore size and pore size distribution were not affected. Although highly porous, the scaffold had relatively small pores and limited interconnectivity. The porous gelatin-alginate scaffold demonstrated excellent biocompatibility with neovascularization on the surfaces and was bioresorbed completely in vivo, depending upon the cross-link density. MSCs were able to attach and proliferate at the same rate on the scaffolds, and the self-renewal potential of MSC cultures was similar during both in vitro culture and in vivo implantation. However, the subcutaneous microenvironment was found to suppress MSC differentiation along the osteogenic, chondrogenic and adipogenic lineages compared to in vitro conditions, highlighting the differential responses of MSCs cultured in vitro compared to implantation in vivo.

摘要

组织工程和干细胞治疗具有很大的潜力,能够完全恢复、修复和替代体内受损、患病或丢失的组织。生物相容性多孔支架用于将细胞递送到再生部位。骨髓基质细胞(MSCs),也称为间充质干细胞,由于其易于分离以及体外扩增的 MSCs 能够生成多种细胞类型的能力,包括成骨细胞、软骨细胞和脂肪细胞,因此是组织工程的一种有吸引力的细胞来源。本研究利用一种称为微波真空干燥的新技术来制造用于递送 MSCs 的多孔明胶-藻酸盐支架,并研究了在这些支架上接种的 MSCs 的体外和体内差异反应。发现支架的总孔隙率随交联密度的增加而降低,但孔径和孔径分布不受影响。尽管具有高度多孔性,但支架的孔较小且连通性有限。多孔明胶-藻酸盐支架具有极好的生物相容性,表面有新生血管形成,并根据交联密度在体内完全生物吸收。MSCs 能够以相同的速度附着和增殖在支架上,MSC 培养物的自我更新潜力在体外培养和体内植入期间相似。然而,与体外条件相比,发现皮下微环境抑制了 MSC 沿着成骨、软骨和成脂谱系的分化,突出了体外培养的 MSC 与体内植入的 MSC 的差异反应。

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