Impact of TGF-β family-related growth factors on chondrogenic differentiation of adipose-derived stem cells isolated from lipoaspirates and infrapatellar fat pads of osteoarthritic patients.
Impact of TGF-β family-related growth factors on chondrogenic differentiation of adipose-derived stem cells isolated from lipoaspirates and infrapatellar fat pads of osteoarthritic patients.
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DOI：
10.22203/ecm.v035a15
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发表时间：
2018-04-13
影响因子：
3.1
通讯作者：
Perán M
中科院分区：
文献类型：
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作者：
López-Ruiz E;Jiménez G;Kwiatkowski W;Montañez E;Arrebola F;Carrillo E;Choe S;Marchal JA;Perán M
用于治疗软骨缺损的基于细胞的方法的成功需要具有软骨分化能力的最佳自体细胞来源，其在植入后保持其分化特性和稳定性。本研究的目的是比较从骨关节炎患者的脂肪抽吸物（ASC）和髌下脂肪垫（IFPSC）中分离的间充质干细胞（MSC）的软骨形成能力，并用转化生长因子（TGF）-β家族相关生长因子处理。将细胞在具有嵌合激活素A/骨形态发生蛋白（BMP）-2配体（AB 235）、嵌合nodal/BMP-2配体（NB 260）或BMP-2的3D沉淀培养系统中培养6周。为了研究新软骨的稳定性，将ASC处理的颗粒皮下移植到严重联合免疫缺陷（SCID）小鼠中。组织学和免疫组织化学评估证实，生长因子诱导软骨分化的两种分离的细胞类型。然而，逆转录定量PCR结果显示，ASCs呈现出更高的软骨形成潜力比IFPSC。体内实验结果显示，与NB 260处理的颗粒相比，AB 235处理的ASCs颗粒尺寸更大，并且可以形成稳定的软骨样组织，而BMP-2处理的颗粒发生钙化。通过免疫荧光分析证明，AB 235处理的ASCs的软骨诱导是由SMAD 2/3激活介导的。这项研究的结果表明，ASCs和AB 235的组合可能导致基于细胞的软骨再生治疗。
The success of cell-based approaches for the treatment of cartilage defects requires an optimal autologous cell source with chondrogenic differentiation ability that maintains its differentiated properties and stability following implantation. The objective of this study was to compare the chondrogenic capacity of mesenchymal stem cells (MSCs) isolated from lipoaspirates (ASCs) and infrapatellar fat pads (IFPSCs) of osteoarthritic patients and treated with transforming growth factor (TGF)-β family-related growth factors. Cells were cultured for 6 weeks in a 3D pellet culture system with the chimeric activin A/bone morphogenic protein (BMP)-2 ligand (AB235), the chimeric nodal/BMP-2 ligand (NB260) or BMP-2. To investigate the stability of the new cartilage, ASCs-treated pellets were transplanted subcutaneously into severe combined immunodeficiency (SCID) mice. Histological and immunohistochemical assessment confirmed that the growth factors induced cartilage differentiation in both isolated cell types. However, reverse transcription-quantitative PCR results showed that ASCs presented a higher chondrogenic potential than IFPSCs. In vivo results revealed that AB235-treated ASCs pellets were larger in size and could form stable cartilage-like tissue as compared to NB260-treated pellets, while BMP-2-treated pellets underwent calcification. The chondrogenic induction of ASCs by AB235 treatment was mediated by SMAD2/3 activation, as proved by immunofluorescence analysis. The results of this study indicated that the combination of ASCs and AB235 might lead to a cell-based cartilage regeneration treatment.