Sasaki T, Akagi R, Akatsu Y, Fukawa T, Hoshi H, Yamamoto Y, Enomoto T, Sato Y, Nakagawa R, Takahashi K, Yamaguchi S, Sasho T
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Department of Orthopaedic Surgery, Graduate School of Medicine, and the Center for Preventive Medicine, Chiba University, 1-8-1 Inohana, Chuoku, Chiba, 260-8670, Japan
Bone Joint Res. 2017 Mar;6(3):123-131. doi: 10.1302/2046-3758.63.BJR-2016-0083.
The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation and to determine whether pre-microfracture systemic administration of G-CSF (a bone marrow stimulant) could improve the quality of repaired tissue of a full-thickness cartilage defect in a rabbit model.
MSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 μg, high-dose: 40 μg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium.A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 μg/kg of G-CSF daily, the high-dose group (n = 10) received 50 μg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically.
The cell count in the low-dose G-CSF medium was significantly higher than that in the control medium. The differentiation potential of MSCs was preserved after culturing them with G-CSF.Macroscopically, defects were filled and surfaces were smoother in the G-CSF groups than in the control group at four weeks. At 12 weeks, the quality of repaired cartilage improved further, and defects were almost completely filled in all groups. Microscopically, at four weeks, defects were partially filled with hyaline-like cartilage in the G-CSF groups. At 12 weeks, defects were repaired with hyaline-like cartilage in all groups.
G-CSF promoted proliferation of MSCs . The systemic administration of G-CSF promoted the repair of damaged cartilage possibly through increasing the number of MSCs in a rabbit model.: T. Sasaki, R. Akagi, Y. Akatsu, T. Fukawa, H. Hoshi, Y. Yamamoto, T. Enomoto, Y. Sato, R. Nakagawa, K. Takahashi, S. Yamaguchi, T. Sasho. The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism: G-CSF for cartilage repair. 2017;6:123-131. DOI: 10.1302/2046-3758.63.BJR-2016-0083.
本研究旨在探讨粒细胞集落刺激因子（G-CSF）对间充质干细胞（MSC）增殖的影响，并确定在兔模型中，微骨折术前全身给予G-CSF（一种骨髓刺激剂）是否能改善全层软骨缺损修复组织的质量。
将兔的间充质干细胞在对照培养基和含G-CSF的培养基（低剂量：4μg，高剂量：40μg）中培养。培养1天、3天和5天后进行细胞计数。通过用成骨、成脂和成软骨培养基刺激培养的细胞来检测其分化潜能。总共30只兔分为三组。低剂量组（n = 10）每天皮下注射10μg/kg的G-CSF，高剂量组（n = 10）在制造软骨缺损前三天每天皮下注射50μg/kg，共三天。对照组（n = 10）连续三天给予生理盐水。首次注射后48小时，在股骨滑车处制造一个直径5.2mm的圆柱形骨软骨缺损。术后4周和12周，对修复组织进行宏观和微观评估。
低剂量G-CSF培养基中的细胞计数显著高于对照培养基中的细胞计数。用G-CSF培养后，间充质干细胞的分化潜能得以保留。宏观上，4周时G-CSF组的缺损被填充，表面比对照组更光滑。12周时，所有组修复软骨的质量进一步改善，缺损几乎完全被填充。微观上，4周时G-CSF组的缺损部分被透明软骨样组织填充。12周时，所有组的缺损均由透明软骨样组织修复。
G-CSF促进间充质干细胞的增殖。在兔模型中，全身给予G-CSF可能通过增加间充质干细胞的数量促进受损软骨的修复。：T. Sasaki、R. Akagi、Y. Akatsu、T. Fukawa、H. Hoshi、Y. Yamamoto、T. Enomoto、Y. Sato、R. Nakagawa、K. Takahashi、S. Yamaguchi、T. Sasho。全身给予G-CSF对兔模型全层软骨缺损的影响 间充质干细胞增殖作为推测机制：用于软骨修复的G-CSF。2017；6：123 - 131。DOI：10.1302/2046 - 3758.63.BJR - 2016 - 0083。
