Improving the immunosuppressive potential of articular chondroprogenitors in a three-dimensional culture setting.

Improving the immunosuppressive potential of articular chondroprogenitors in a three-dimensional culture setting.
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DOI:
10.1038/s41598-020-73188-9
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发表时间:
2020-10-06
期刊:
影响因子:
4.6
通讯作者:
Taraballi F
Taraballi F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bauza G;Pasto A;Mcculloch P;Lintner D;Brozovich A;Niclot FB;Khan I;Francis LW;Tasciotti E;Taraballi F

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骨关节炎患者的腕关节修复仍然是一个挑战。鉴定宿主或供体干/祖细胞群对于增强透明软骨的低内在修复潜力至关重要。此外,介导这些细胞和局部免疫原性环境之间的相互作用被认为是长期修复和再生的关键。在这项研究中,我们提出关节软骨祖细胞/干细胞(CPSC)作为一个有效的替代骨髓间充质干细胞(BMMSC)的软骨修复策略创伤后。与BMMSC相似,从骨关节炎患者中分离的CPSC表达干细胞标志物,并具有软骨形成、成骨和成脂分化能力。在体外2D环境中,CPSC显示出SPP1和LEP(分别为成骨和成脂分化的标志物)的较高表达。CPSC还显示出更高的软骨形成承诺,如通过ACAN的更高表达所证明的。使用先前建立的胶原-硫酸软骨素3D支架体外培养BMMSC和CPSC。该支架模拟软骨生态位,允许两种细胞群保持其干细胞特征并提高其免疫抑制潜力,这通过在共培养环境中抑制活化的PBMC增殖来证明。因此,这项研究表明,关节软骨衍生的CPSC可用作骨关节炎(OA)细胞和脱细胞再生医学方法的新工具。此外,利用仿生脱细胞支架作为先进的3D培养系统,以更准确地模拟生理环境的好处被证明。
Cartilage repair in osteoarthritic patients remains a challenge. Identifying resident or donor stem/progenitor cell populations is crucial for augmenting the low intrinsic repair potential of hyaline cartilage. Furthermore, mediating the interaction between these cells and the local immunogenic environment is thought to be critical for long term repair and regeneration. In this study we propose articular cartilage progenitor/stem cells (CPSC) as a valid alternative to bone marrow-derived mesenchymal stem cells (BMMSC) for cartilage repair strategies after trauma. Similar to BMMSC, CPSC isolated from osteoarthritic patients express stem cell markers and have chondrogenic, osteogenic, and adipogenic differentiation ability. In an in vitro 2D setting, CPSC show higher expression of SPP1 and LEP, markers of osteogenic and adipogenic differentiation, respectively. CPSC also display a higher commitment toward chondrogenesis as demonstrated by a higher expression of ACAN. BMMSC and CPSC were cultured in vitro using a previously established collagen-chondroitin sulfate 3D scaffold. The scaffold mimics the cartilage niche, allowing both cell populations to maintain their stem cell features and improve their immunosuppressive potential, demonstrated by the inhibition of activated PBMC proliferation in a co-culture setting. As a result, this study suggests articular cartilage derived-CPSC can be used as a novel tool for cellular and acellular regenerative medicine approaches for osteoarthritis (OA). In addition, the benefit of utilizing a biomimetic acellular scaffold as an advanced 3D culture system to more accurately mimic the physiological environment is demonstrated.
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