Periodic injections of adipose-derived stem cell sheets attenuate osteoarthritis progression in an experimental rabbit model.

Periodic injections of adipose-derived stem cell sheets attenuate osteoarthritis progression in an experimental rabbit model.
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DOI:
10.1186/s12891-020-03718-z
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发表时间:
2020-10-19
影响因子:
2.3
通讯作者:
Tsuchiya H
Tsuchiya H
中科院分区:
医学3区
文献类型:
--
作者:
Takagi T;Kabata T;Hayashi K;Fang X;Kajino Y;Inoue D;Ohmori T;Ueno T;Yoshitani J;Ueoka K;Yamamuro Y;Tsuchiya H

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皮下脂肪组织具有丰富的多潜能成体干细胞来源,称为脂肪来源干细胞(ADSCs)。通过细胞片法,ADSC的寿命更长,并且可以大量交付。我们在兔前交叉韧带横断术(ACLT)模型上研究了关节内ADSC片是否能减缓骨关节炎(OA)的进展。用含有抗坏血酸-2-磷酸的制备介质促进ADSC分泌胶原蛋白,制成ADSC片材。术后4 ,右侧膝关节内注射自体ADSC片剂(ADSC片组),左侧膝关节注射液氮处理的自体细胞死亡片剂(对照组)。随后的注射每周进行一次。从大体和组织学角度对股骨髁进行比较。从宏观上看,ADSC组的OA进展明显比对照组平缓。在组织学上,对照组膝关节内侧和外侧有明显的侵蚀,而ADSC钢板组主要保留软骨。免疫组织化学显示,基质金属蛋白酶-1、基质金属蛋白酶-13、基质金属蛋白酶-4在脂肪间充质干细胞板层中的表达均低于对照组。定期注射ADSC片剂可抑制关节软骨退变,且不会产生任何不良反应。大量的自体ADSCs通过细胞膜运送到滑膜并保护软骨细胞。
Subcutaneous adipose tissue represents an abundant source of multipotent adult stem cells named as Adipose-derived stem cells (ADSCs). With a cell sheet approach, ADSCs survive longer, and can be delivered in large quantities. We investigated whether intra-articular ADSC sheets attenuated osteoarthritis (OA) progression in a rabbit anterior cruciate ligament transection (ACLT) model. Fabricating medium containing ascorbate-2-phosphate was used to enhance collagen protein secretion by the ADSCs to make ADSC sheets. At 4 weeks after ACLT, autologous ADSC sheets were injected intra-articularly into the right knee (ADSC sheets group), and autologous cell death sheets treated by liquid nitrogen were injected into the left knee (control group). Subsequent injections were administered once weekly. Femoral condyles were compared macroscopically and histologically. Macroscopically, OA progression was significantly milder in the ADSC sheets than in the control groups. Histologically, control knees showed obvious erosions in the medial and lateral condyles, while cartilage was retained predominantly in the ADSC sheets group. Immunohistochemically, MMP-1, MMP-13, ADAMTS-4 were less expressive in the ADSC sheets than in the control groups. Periodic ADSC sheets injections inhibited articular cartilage degeneration without inducing any adverse effects. A large quantity of autologous ADSCs delivered by cell sheets homed to the synovium and protected chondrocytes.
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