脂肪源干细胞移植骨质疏松模型大鼠骨密度及骨形态计量学指标的变化

Adipose-derived stem cell transplantation for osteoporosis rats: evaluation by bone mineral density and histomorphometry measurement

背景:越来越多的研究者希望通过干细胞移植促进成骨细胞分化,抑制破骨细胞增殖,从而治疗骨质疏松症。目的:探讨外源性脂肪干细胞移植对卵巢切除骨质疏松大鼠的治疗作用。方法:选取30只SD雌性大鼠随机分为假手术组、模型组、脂肪干细胞移植组,每组10只。模型组和脂肪干细胞移植组进行双侧卵巢切除手术,建立骨质疏松模型,假手术组仅摘除卵巢附近的脂肪组织,但不摘除卵巢。脂肪干细胞移植组经尾静脉注射第4代脂肪干细胞(2×106个脂肪干细胞),模型组注射等量生理盐水,每周1次。细胞移植6周后,检测血清钙、磷、碱性磷酸酶水平及骨密度、骨形态计量学指标。结果与结论:(1)与假手术组相比,模型组大鼠胫骨骨小梁体积百分比明显降低(P<0.01),与模型组相比,脂肪干细胞移植组大鼠胫骨骨小梁体积百分比显著增加,差异有显著性意义(P<0.05);(2)与假手术组相比,模型组大鼠胫骨骨小梁吸收表面百分比、骨小梁形成表面百分比明显升高(P<0.05或P<0.01);与模型组相比,脂肪干细胞移植组大鼠胫骨骨小梁吸收表面百分比、骨小梁形成表面百分比显著降低,差异有显著性意义(P<0.05);(3)与假手术组相比,模型组血清钙、碱性磷酸酶水平和骨密度显著降低(P<0.05),而血清磷水平显著升高(P<0.05);与模型组相比,脂肪干细胞移植组血清钙、碱性磷酸酶水平和骨密度显著升高(P<0.05),而血清磷水平显著降低(P<0.05);(4)结果表明,脂肪干细胞移植后能够改善卵巢切除骨质疏松大鼠的骨量流失。

BACKGROUND： Stem cell transplantation is increasingly hoped to promote osteoblast differentiation and inhibit osteoclast proliferation in the treatment of osteoporosis.OBJECTIVE： To study the therapeutic effect of exogenous adipose-derived stem cell（ADSC）transplantation on osteoporosis in ovariectomized rats.METHODS： Thirty Sprague-Dawley female rats were equivalently randomized into sham, model, ADSC transplantation groups. Rats in all groups except the sham group underwent bilateral ovariectomy to make osteoporosis models. Surrounding adipose tissues instead of the ovary were removed in the sham group.After modeling, rats were given 2×10~6 ADSCs at passage 4 via the tail vein in the transplantation group and the same volume of normal saline in the model group, once a week. After 6 weeks, levels of serum calcium, phosphorus, and alkaline phosphatase as well as bone mineral density and histomorphometry indicators were detected in rats.RESULTS AND CONCLUSION： Compared with the sham group, the trabecular bone volume fraction was significantly decreased in the model group（P 0.01）, but remarkably increased after ADSC transplantation（P〈0.05）. After modeling, the bone trabecular absorption surface percentage and rate of bone trabecular formation were elevated significantly（P〈0.05 or P 〈0.01）, while these increases were improved by ADSC transplantation（P〈0.05）. Additionally, the levels of serum calcium and alkaline phosphatase and bone mineral density were significantly decreased after modeling, but were increased after ADSC transplantation. In contrast, the serum level of phosphorus was significantly increased in the model group（P〈0.05） but decreased markedly in the ADSC transplantation group（P〈0.05）. To conclude, ADSC transplantation can reduce the loss of bone mass in osteoporosis rats by ovariectomy.