Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, People's Republic of China.
Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, People's Republic of China.
Stem Cell Res Ther. 2024 Jan 17;15(1):18. doi: 10.1186/s13287-024-03632-4.
Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) offer promising prospects for stimulating cartilage regeneration. The different formation mechanisms suggest that exosomes and ectosomes possess different biological functions. However, little attention has been paid to the differential effects of EV subsets on cartilage regeneration.
Our study compared the effects of the two EVs isolated from adipose-derived MSCs (ASCs) on chondrocytes and bone marrow-derived MSCs (BMSCs) in vitro. Additionally, we loaded the two EVs into type I collagen hydrogels to optimize their application for the treatment of osteochondral defects in vivo.
In vitro experiments demonstrate that ASC-derived exosomes (ASC-Exos) significantly promoted the proliferation and migration of both cells more effectively than ASC-derived ectosomes (ASC-Ectos). Furthermore, ASC-Exos facilitated a stronger differentiation of BMSCs into chondrogenic cells than ASC-Ectos, but both inhibited chondrocyte apoptosis to a similar extent. In the osteochondral defect model of rats, ASC-Exos promoted cartilage regeneration in situ better than ASC-Ectos. At 8 weeks, the hydrogel containing exosomes group (Gel + Exo group) had higher macroscopic and histological scores, a higher value of trabecular bone volume fraction (BV/TV), a lower value of trabecular thickness (Tb.Sp), and a better remodeling of extracellular matrix than the hydrogel containing ectosomes group (Gel + Ecto group). At 4 and 8 weeks, the expression of CD206 and Arginase-1 in the Gel + Exo group was significantly higher than that in the Gel + Ecto group.
Our findings indicate that administering ASC-Exos may be a more effective EV strategy for cartilage regeneration than the administration of ASC-Ectos.
源自间充质基质细胞（MSCs）的细胞外囊泡（EVs）为刺激软骨再生提供了有前景的前景。不同的形成机制表明，外泌体和ectosomes 具有不同的生物学功能。然而，对于 EV 亚群对软骨再生的差异影响，关注甚少。
我们的研究比较了从脂肪来源的间充质干细胞（ASCs）分离的两种 EVs 在体外对软骨细胞和骨髓来源的间充质干细胞（BMSCs）的影响。此外，我们将这两种 EVs 载入 I 型胶原水凝胶中，以优化其在体内治疗骨软骨缺损的应用。
体外实验表明，ASC 衍生的外泌体（ASC-Exos）比 ASC 衍生的 ectosomes（ASC-Ectos）更有效地显著促进两种细胞的增殖和迁移。此外，ASC-Exos 促进 BMSCs 向软骨细胞分化的能力强于 ASC-Ectos，但两者对软骨细胞凋亡的抑制作用相似。在大鼠的骨软骨缺损模型中，ASC-Exos 在体内促进软骨再生的效果优于 ASC-Ectos。在 8 周时，含有外泌体的水凝胶组（Gel+Exo 组）的宏观和组织学评分较高，骨小梁体积分数（BV/TV）值较高，骨小梁厚度（Tb.Sp）值较低，细胞外基质重塑较好，明显优于含有 ectosomes 的水凝胶组（Gel+Ecto 组）。在 4 周和 8 周时，Gel+Exo 组的 CD206 和精氨酸酶-1 的表达明显高于 Gel+Ecto 组。
我们的研究结果表明，与给予 ASC-Ectos 相比，给予 ASC-Exos 可能是一种更有效的 EV 策略，用于软骨再生。
