Uzieliene Ilona, Bironaite Daiva, Pachaleva Jolita, Bagdonas Edvardas, Sobolev Arkadij, Tsai Wei-Bor, Kvedaras Giedrius, Bernotiene Eiva
Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania.
Latvian Institute of Organic Synthesis, LV-1006 Riga, Latvia.
Int J Mol Sci. 2023 Feb 9;24(4):3451. doi: 10.3390/ijms24043451.
The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr/Gel/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher release of ECM components, such as the cartilage oligomeric matrix protein (COMP) and GAGs, compared to the not-compressed explants. Finally, the application of the CS-Tyr/Gel/BM-MSCs composite on the top of the OA cartilage explants decreased the release of COMP and GAGs from the cartilage explants. Data suggest that the CS-Tyr/Gel/BM-MSCs composite can protect the OA cartilage explants from the damaging effects of external mechanical stimuli. Therefore, it can be used for investigation of OA cartilage regenerative potential and mechanisms under the mechanical load in vitro with further perspectives of therapeutic application in vivo.
由于创伤、机械负荷或疾病导致的软骨降解，会致使细胞外基质（ECM）完整性大量丧失，并引发骨关节炎（OA）。硫酸软骨素（CS）是高度硫酸化糖胺聚糖（GAGs）的成员之一，也是软骨组织ECM的主要成分。在本研究中，我们旨在探究机械负荷对封装于CS-酪胺-明胶（CS-Tyr/Gel）水凝胶中的骨髓间充质干细胞（BM-MCSs）软骨分化的影响，以评估这种复合材料在体外OA软骨再生研究中的适用性。CS-Tyr/Gel/BM-MSCs复合材料在软骨外植体上表现出优异的生物整合性。施加的轻度机械负荷刺激了CS-Tyr/Gel水凝胶中BM-MSCs的软骨分化（免疫组织化学胶原II染色）。然而，与未压缩的外植体相比，更强的机械负荷对人OA软骨外植体产生了负面影响，表现为ECM成分如软骨寡聚基质蛋白（COMP）和GAGs的释放增加。最后，将CS-Tyr/Gel/BM-MSCs复合材料应用于OA软骨外植体顶部，减少了软骨外植体中COMP和GAGs的释放。数据表明，CS-Tyr/Gel/BM-MSCs复合材料可以保护OA软骨外植体免受外部机械刺激的破坏作用。因此，它可用于体外研究机械负荷下OA软骨的再生潜力和机制，并具有进一步体内治疗应用的前景。
