Oxygen tension differentially regulates the functional properties of cartilaginous tissues engineered from infrapatellar fat pad derived MSCs and articular chondrocytes
Oxygen tension differentially regulates the functional properties of cartilaginous tissues engineered from infrapatellar fat pad derived MSCs and articular chondrocytes
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DOI：
10.1016/j.joca.2010.07.004
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发表时间：
2010-10-01
影响因子：
7
通讯作者：
Kelly, D. J.
中科院分区：
文献类型：
--
作者：
Buckley, C. T.;Vinardell, T.;Kelly, D. J.
背景资料：对于目前的组织工程或再生医学策略，软骨细胞（CC）或间充质干细胞（MSC）接种的构建体通常在常氧条件（20%氧气）下培养。然而，在膝关节囊较低的氧张力existing.Objective：本研究的目的是探讨如何在3D琼脂糖培养的CC和髌下脂肪垫来源的骨髓间充质干细胞将响应于低氧（5%）环境。我们的假设是在低氧环境（5%）中培养将增强使用两种细胞来源工程化的软骨组织的功能特性。细胞包封的琼脂糖水凝胶构建体制备（接种有CC或髌下脂肪垫（IFP）衍生的MSC），并在化学成分确定的无血清培养基中在存在下培养。（CC和MSC）或不存在（仅CC）转化生长因子-β 3（TGF-β 3）在常氧（20%）或低氧（5%）条件下42天。构建体进行了评估，在第0，21和42天的机械性能，生化含量和histologic.Results：低氧张力（5%），观察到促进细胞外基质（ECM）的生产，在没有TGF-β 3的情况下培养的CC，但在TGF-β 3的存在下抑制。相比之下，低氧张力增强的TGF-β 3的存在下，IFP结构的软骨形成，导致上级机械功能相比，CC培养在相同的conditions.Conclusions：外推本研究的结果在体内设置，它会出现，联合脂肪垫来源的间充质干细胞可能具有上级潜力，产生一个功能性修复组织在低氧张力。然而，在体外软骨组织工程的背景下，在TGF-β 3存在下保持在常氧条件下的CC产生最具机械功能的组织。(C)2010年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Background: For current tissue engineering or regenerative medicine strategies, chondrocyte (CC)- or mesenchymal stem cell (MSC)-seeded constructs are typically cultured in normoxic conditions (20% oxygen). However, within the knee joint capsule a lower oxygen tension exists.Objective: The objective of this study was to investigate how CCs and infrapatellar fad pad derived MSCs will respond to a low oxygen (5%) environment in 3D agarose culture. Our hypothesis was that culture in a low oxygen environment (5%) will enhance the functional properties of cartilaginous tissues engineered using both cell sources.Experimental design: Cell-encapsulated agarose hydrogel constructs (seeded with CCs or infrapatellar fat pad (IFP) derived MSCs) were prepared and cultured in a chemically defined serum-free medium in the presence (CCs and MSCs) or absence (CCs only) of transforming growth factor-beta3 (TGF-beta 3) in normoxic (20%) or low oxygen (5%) conditions for 42 days. Constructs were assessed at days 0, 21 and 42 in terms of mechanical properties, biochemical content and histologically.Results: Low oxygen tension (5%) was observed to promote extracellular matrix (ECM) production by CCs cultured in the absence of TGF-beta 3, but was inhibitory in the presence of TGF-beta 3. In contrast, a low oxygen tension enhanced chondrogenesis of IFP constructs in the presence of TGF-beta 3, leading to superior mechanical functionality compared to CCs cultured in identical conditions.Conclusions: Extrapolating the results of this study to the in vivo setting, it would appear that joint fat pad derived MSCs may possess a superior potential to generate a functional repair tissue in low oxygen tensions. However, in the context of in vitro cartilage tissue engineering, CCs maintained in normoxic conditions in the presence of TGF-beta 3 generate the most mechanically functional tissue. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.