Hydrogels derived from cartilage matrices promote induction of human mesenchymal stem cell chondrogenic differentiation
Hydrogels derived from cartilage matrices promote induction of human mesenchymal stem cell chondrogenic differentiation
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DOI：
10.1016/j.actbio.2016.07.034
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发表时间：
2016-10-01
影响因子：
9.7
通讯作者：
Boyan, Barbara D.
中科院分区：
文献类型：
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作者：
Burnsed, Olivia A.;Schwartz, Zvi;Boyan, Barbara D.
健康的自体或同种异体软骨来源的有限供应激发了对异种软骨基质作为软骨组织工程的生物支架的日益增长的兴趣。本研究的目的是确定鲨鱼和猪软骨细胞外基质（ECM）水凝胶是否可以刺激间充质干细胞（MSC）的软骨细胞分化，而无需外源性生长因子，并确定这些ECM水凝胶保留的可溶性因子是否负责。与在组织培养聚苯乙烯（TCPS）上培养的MSC相比，在来自鲨鱼头骨软骨、猪关节软骨和猪耳软骨ECM的水凝胶上培养的人MSC在一周时软骨细胞标志物的表达增加，血管生成因子VEGF-A和FGF 2的分泌减少。与所有其他组相比，在鲨鱼ECM凝胶上生长的MSC具有降低的1型胶原mRNA。软骨ECM凝胶的降解产物和基质释放的可溶性因子增加了软骨形成和降低了血管生成mRNA水平，表明经处理的ECM保留了可刺激软骨形成分化的生物化学活性蛋白。总之，这项工作支持使用软骨基质衍生的水凝胶的间充质干细胞和软骨组织工程的软骨分化。需要更长期的研究和阳性对照来支持这些结果，以明确证明对软骨细胞分化的刺激，本研究的目的是确定鲨鱼和猪软骨细胞外基质（ECM）是否与鲨鱼软骨中的细胞外基质（ECM）相似，水凝胶可以在没有外源生长因子的情况下刺激间充质干细胞（MSC）的软骨细胞分化，并确定这些ECM水凝胶保留的可溶性因子是否负责这种诱导。鲨鱼是软骨再生的一个特别有趣的模型，因为它们的整个骨骼都是由软骨组成的，并且它们不经历软骨内骨化。直接在猪和鲨鱼软骨ECM凝胶上培养人MSC，用ECM凝胶条件培养基或降解产物增加软骨形成因子的mRNA水平，同时减少血管生成因子。这些研究表明，异种软骨ECM具有作为生物可降解支架的潜力，能够刺激软骨形成，同时防止再生医学应用中的血管生成，并且ECM物种选择可以产生不同的效果。(C)2016 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Limited supplies of healthy autologous or allogeneic cartilage sources have inspired a growing interest in xenogeneic cartilage matrices as biological scaffolds for cartilage tissue engineering. The objectives of this study were to determine if shark and pig cartilage extracellular matrix (ECM) hydrogels can stimulate chondrocytic differentiation of mesenchymal stem cells (MSCs) without exogenous growth factors and to determine if the soluble factors retained by these ECM hydrogels are responsible. Human MSCs cultured on hydrogels from shark skull cartilage, pig articular cartilage, and pig auricular cartilage ECM had increased expression of chondrocyte markers and decreased secretion of angiogenic factors VEGF-A and FGF2 in comparison to MSCs cultured on tissue culture polystyrene (TCPS) at one week. MSCs grown on shark ECM gels had decreased type-1 collagen mRNA as compared to all other groups. Degradation products of the cartilage ECM gels and soluble factors released by the matrices increased chondrogenic and decreased angiogenic mRNA levels, indicating that the processed ECM retains biochemically active proteins that can stimulate chondrogenic differentiation. In conclusion, this work supports the use of cartilage matrix-derived hydrogels for chondrogenic differentiation of MSCs and cartilage tissue engineering. Longer-term studies and positive controls will be needed to support these results to definitively demonstrate stimulation of chondrocyte differentiation, and particularly to verify that calcification without endochondral ossification does not occur as it does in shark cartilage.Statement of SignificanceThe objectives of this study were to determine if shark and pig cartilage extracellular matrix (ECM) hydrogels can stimulate chondrocytic differentiation of mesenchymal stem cells (MSCs) without exogenous growth factors and to determine if the soluble factors retained by these ECM hydrogels are responsible for this induction. Sharks are an especially interesting model for cartilage regeneration because their entire skeleton is composed of cartilage and they do not undergo endochondral ossification. Culturing human MSCs on porcine and shark cartilage ECM gels directly, with ECM gel conditioned media, or degradation products increased mRNA levels of chondrogenic factors while decreasing angiogenic factors. These studies indicate that xenogeneic cartilage ECMs have potential as biodegradable scaffolds capable of stimulating chondrogenesis while preventing angiogenesis for regenerative medicine applications and that ECM species selection can yield differential effects. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.