Stem Cell-Based Meniscus Tissue Engineering

Stem Cell-Based Meniscus Tissue Engineering
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DOI:
10.1089/ten.tea.2011.0031
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发表时间:
2011-11-01
影响因子:
4.1
通讯作者:
Kaplan, David L.
Kaplan, David L.
中科院分区:
医学3区
文献类型:
--
作者:
Mandal, Biman B.;Park, Sang-Hyug;Kaplan, David L.

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膝关节半月板是一种纤维软骨组织,其特征在于细胞外基质(ECM)和生物力学特性的异质性,并且对于膝关节内的矫形稳定性、载荷传递、减震和应力分布至关重要。由于半月板的部分无血管性质,大多数半月板损伤不能被身体有效治愈;因此,损伤或年龄引起的损伤损害正常的膝关节功能,使患者易患骨关节炎。半月板组织工程提供了一种可能的解决方案,通过产生替代组织,可以植入到缺损部位,以模仿自然半月板组织的功能。为了解决这一需求,使用丝蛋白支架和干细胞形成多孔、多层半月板。将人骨髓干细胞接种在蚕丝支架上,并在转化生长因子β 3存在下在软骨形成培养物中随时间分化,以在体外产生类软骨组织。高水平的I型和II型胶原蛋白、硫酸化糖胺聚糖沿着增强的胶原蛋白1-α 1、聚集蛋白聚糖和SOX 9基因表达进一步证实了分化和成熟的细胞表型。这项研究的结果是一个向前迈进的生物力学能力半月板工程,重建天然半月板的形式和功能。
Knee meniscus, a fibrocartilaginous tissue, is characterized by heterogeneity in extracellular matrix (ECM) and biomechanical properties, and critical for orthopedic stability, load transmission, shock absorption, and stress distribution within the knee joint. Most damage to the meniscus cannot be effectively healed by the body due to its partial avascular nature; thus, damage caused by injury or age impairs normal knee function, predisposing patients to osteoarthritis. Meniscus tissue engineering offers a possible solution to this problem by generating replacement tissue that may be implanted into the defect site to mimic the function of natural meniscal tissue. To address this need, a multiporous, multilamellar meniscus was formed using silk protein scaffolds and stem cells. The silk scaffolds were seeded with human bone marrow stem cells and differentiated over time in chondrogenic culture in the presence of transforming growth factor-beta 3 to generate meniscus-like tissue in vitro. High cellularity along with abundant ECM leading to enhanced biomechanics similar to native tissue was found. Higher levels of collagen type I and II, sulfated glycosaminoglycans along with enhanced collagen 1-alpha 1, aggrecan, and SOX9 gene expression further confirmed differentiation and matured cell phenotype. The results of this study are a step forward toward biomechanically competent meniscus engineering, reconstituting both form and function of the native meniscus.