明胶微球负载牙髓间充质干细胞移植促进小鼠软骨修复。

Transplantation of Gelatin Microspheres Loaded with Wharton's Jelly Derived Mesenchymal Stem Cells Facilitates Cartilage Repair in Mice.

机构信息

MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China.

Key Laboratory of Reproductive Medicine of Guangdong Province, The First Affliated Hospital and School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China.

出版信息

Tissue Eng Regen Med. 2024 Jan;21(1):171-183. doi: 10.1007/s13770-023-00574-5. Epub 2023 Sep 9.

DOI:10.1007/s13770-023-00574-5

PMID:37688747

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10764672/

Abstract

BACKGROUND

Knee osteoarthritis (KOA) is a prevalent chronic joint disease caused by various factors. Mesenchymal stem cells (MSCs) therapy is an increasingly promising therapeutic option for osteoarthritis. However, the chronic inflammation of knee joint can severely impede the therapeutic effects of transplanted cells. Gelatin microspheres (GMs) are degradable biomaterial that have various porosities for cell adhesion and cell-cell interaction. Excellent elasticity and deformability of GMs make it an excellent injectable vehicle for cell delivery.

METHODS

We created Wharton's jelly derived mesenchymal stem cells (WJMSCs)-GMs complexes and assessed the effects of GMs on cell activity, proliferation and chondrogenesis. Then, WJMSCs loaded in GMs were transplanted in the joint of osteoarthritis mice. After four weeks, joint tissue was collected for histological analysis. Overexpressing-luciferase WJMSCs were performed to explore cell retention in mice.

RESULTS

In vitro experiments demonstrated that WJMSCs loaded with GMs maintained cell viability and proliferative potential. Moreover, GMs enhanced the chondrogenesis differentiation of WJMSCs while alleviated cell hypertrophy. In KOA mice model, transplantation of WJMSCs-GMs complexes promoted cartilage regeneration and cartilage matrix formation, contributing to the treatment of KOA. Compared with other groups, in WJMSCs+GMs group, there were fewer cartilage defects and with a more integrated tibia structure. Tracking results of stable-overexpressing luciferase WJMSCs demonstrated that GMs significantly extended the retention time of WJMSCs in knee joint cavity.

CONCLUSION

Our results indicated that GMs facilitate WJMSCs mediated knee osteoarthritis healing in mice by promoting cartilage regeneration and prolonging cell retention. It might potentially provide an optimal strategy for the biomaterial-stem cell based therapy for knee osteoarthritis.

摘要

背景

膝骨关节炎（KOA）是一种由多种因素引起的常见慢性关节疾病。间充质干细胞（MSCs）治疗是一种治疗骨关节炎的新兴治疗选择。然而，膝关节的慢性炎症会严重阻碍移植细胞的治疗效果。明胶微球（GMs）是一种可降解的生物材料，具有各种有利于细胞黏附和细胞间相互作用的孔隙。GMs 具有极好的弹性和可变形性，是细胞递送的理想可注射载体。

方法

我们构建了 Wharton 胶来源的间充质干细胞（WJMSCs）-GMs 复合物，并评估了 GMs 对细胞活性、增殖和软骨生成的影响。然后，将负载 WJMSCs 的 GMs 移植到骨关节炎小鼠的关节中。四周后，收集关节组织进行组织学分析。进行过表达荧光素酶的 WJMSCs 实验以探索细胞在小鼠体内的保留情况。

结果

体外实验表明，负载 GMs 的 WJMSCs 保持了细胞活力和增殖潜力。此外，GMs 增强了 WJMSCs 的软骨分化，同时减轻了细胞肥大。在 KOA 小鼠模型中，WJMSCs-GMs 复合物的移植促进了软骨再生和软骨基质形成，有助于 KOA 的治疗。与其他组相比，在 WJMSCs+GMs 组中，软骨缺陷更少，胫骨结构更完整。稳定过表达荧光素酶的 WJMSCs 的追踪结果表明，GMs 显著延长了 WJMSCs 在膝关节腔内的保留时间。