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在实验性兔模型中，定期注射脂肪来源的干细胞片可减轻骨关节炎的进展。

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

作者信息

Takagi Tomoharu, Kabata Tamon, Hayashi Katsuhiro, Fang Xiang, Kajino Yoshitomo, Inoue Daisuke, Ohmori Takaaki, Ueno Takuro, Yoshitani Junya, Ueoka Ken, Yamamuro Yuki, Tsuchiya Hiroyuki

机构信息

Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.

出版信息

BMC Musculoskelet Disord. 2020 Oct 19;21(1):691. doi: 10.1186/s12891-020-03718-z.

DOI:10.1186/s12891-020-03718-z
PMID:33076883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7574575/
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

皮下脂肪组织是多能成体干细胞的丰富来源，这些细胞被称为脂肪来源干细胞（ADSCs）。采用细胞片技术，ADSCs存活时间更长，且能大量递送。我们研究了关节内注射ADSC片是否能在兔前交叉韧带切断（ACLT）模型中减缓骨关节炎（OA）的进展。

方法

使用含抗坏血酸-2-磷酸的培养基增强ADSCs分泌胶原蛋白以制备ADSC片。ACLT术后4周，将自体ADSC片关节内注射到右膝（ADSC片组），将经液氮处理的自体细胞死亡片注射到左膝（对照组）。随后每周注射一次。对股骨髁进行宏观和组织学比较。

结果

宏观上，ADSC片组的OA进展明显比对照组轻。组织学上，对照膝关节的内外侧髁显示出明显侵蚀，而ADSC片组的软骨主要得以保留。免疫组织化学显示，ADSC片组中基质金属蛋白酶-1（MMP-1）、基质金属蛋白酶-13（MMP-13）、含血小板反应蛋白基序的解聚素样金属蛋白酶-4（ADAMTS-4）的表达低于对照组。

结论

定期注射ADSC片可抑制关节软骨退变且未引起任何不良反应。通过细胞片递送的大量自体ADSCs归巢至滑膜并保护软骨细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/3425974462ba/12891_2020_3718_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/a8e17599b193/12891_2020_3718_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/e8ce0d60358a/12891_2020_3718_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/270b36603ce1/12891_2020_3718_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/43565587c8a7/12891_2020_3718_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/ca3e83beabbf/12891_2020_3718_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/eea3ad9ed1f2/12891_2020_3718_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/2fe84b52f913/12891_2020_3718_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/59d08e536cb3/12891_2020_3718_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/3425974462ba/12891_2020_3718_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/a8e17599b193/12891_2020_3718_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/e8ce0d60358a/12891_2020_3718_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/270b36603ce1/12891_2020_3718_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/43565587c8a7/12891_2020_3718_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/ca3e83beabbf/12891_2020_3718_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/eea3ad9ed1f2/12891_2020_3718_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/2fe84b52f913/12891_2020_3718_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/59d08e536cb3/12891_2020_3718_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3c/7574575/3425974462ba/12891_2020_3718_Fig9_HTML.jpg

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