Human Adipose Tissue-Derived Stromal Cell Therapy Prevents Bone Loss in Ovariectomized Nude Mouse
Human Adipose Tissue-Derived Stromal Cell Therapy Prevents Bone Loss in Ovariectomized Nude Mouse
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DOI：
10.1089/ten.tea.2011.0355
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发表时间：
2012-05-01
影响因子：
4.1
通讯作者：
Shin, Chan Soo
中科院分区：
文献类型：
--
作者：
Cho, Sun Wook;Sun, Hyun Jin;Shin, Chan Soo
骨质疏松症是一种骨骼疾病，其特征是骨矿物质密度（BMD）降低和骨折风险增加。我们研究了人脂肪组织来源的基质细胞（ADSC）的细胞治疗对T细胞缺陷裸鼠卵巢切除术诱导的骨丢失的影响。对10周龄雌性裸鼠进行卵巢切除术，并用ADSC、雌激素或磷酸盐缓冲盐水（PBS）处理。全身骨密度显示，与PBS对照组相比，ADSC治疗在细胞治疗后对卵巢切除术诱导的骨量增加衰减更具保护作用（8.4 +/-1.1%对2.4% +/-1.4%，p < 0.05，4周时，13.7 +/-1.3%对7.7% +/-1.8%，p < 0.05，8周时），并且该效果与雌激素的效果相当。μ CT分析显示，ADSCs的作用对骨小梁具有特异性。卵巢切除术后4周血清骨钙素水平增加，并且与雌激素（63.1 +/- 6.7 ng/mL，p < 0.05）或PBS治疗（58.0 +/- 9.2 ng/mL，p < 0.05）相比，用ADSC治疗（76.4 +/- 11.6 ng/mL）更大程度地增加骨钙素。PKH 26标记的ADSCs的流式细胞术分析和来自骨的人β-珠蛋白的定量实时PCR分析显示，移植的ADSCs在注射后48 h在骨中运输，随后消失。没有证据表明输注的ADSC在骨中长期植入。在体外，ADSC条件培养基处理增强了基质细胞和前成骨细胞的成骨分化。这些结果表明，脂肪干细胞的细胞治疗保护对卵巢切除术诱导的骨丢失在裸鼠中以旁分泌的方式。
Osteoporosis is a skeletal disorder characterized by reduced bone mineral density (BMD) and increased risk of fracture. We studied the effects of cell therapy of human adipose tissue-derived stromal cell (ADSC) on ovariectomy-induced bone loss in T cell deficient nude mice. Twelve-week-old female nude mice underwent ovariectomy and were treated with ADSC, estrogen, or phosphate buffered saline (PBS). Whole body BMD revealed that treatment of ADSC was more protective against ovariectomy-induced attenuation in bone mass gain compared with PBS control after cell therapy (8.4 +/- 1.1 vs. 2.4% +/- 1.4%, p < 0.05 at 4 weeks, 13.7 +/- 1.3 vs. 7.7% +/- 1.8%, p < 0.05 at 8 weeks) and this effect was comparable to that of estrogen. mu CT analysis revealed that the effect of ADSCs was specific to trabecular bone. Serum osteocalcin levels were increased 4 weeks after ovariectomy and treatment with ADSCs (76.4 +/- 11.6 ng/mL) increased osteocalcin to a greater extent when compared with estrogen (63.1 +/- 6.7 ng/mL, p < 0.05) or PBS treatment (58.0 +/- 9.2 ng/mL, p < 0.05). Flow cytometry analysis for PKH26-labeled ADSCs and quantitative real-time PCR analysis for human beta-globin from bone revealed that transplanted ADSCs were trafficking in bone 48 h after injection and subsequently disappeared. There was no evidence of long-term engraftment of infused ADSCs in bone. In vitro, treatment with ADSC-conditioned medium enhanced osteogenic differentiation in stromal cells and preosteoblasts. These results suggest that cell therapy of ADSCs protects against ovariectomy-induced bone loss in nude mice in a paracrine manner.