Effects of Systemic Transplantation of Adipose Tissue-Derived Stem Cells on Olfactory Epithelium Regeneration

Effects of Systemic Transplantation of Adipose Tissue-Derived Stem Cells on Olfactory Epithelium Regeneration
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DOI:
10.1002/lary.20187
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发表时间:
2009-05-01
期刊:
影响因子:
2.6
通讯作者:
Rha, Ki-Sang
Rha, Ki-Sang
中科院分区:
医学2区
文献类型:
--
作者:
Kim, Yong Min;Choi, Young Seok;Rha, Ki-Sang

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目的/假设:本研究的目的是探讨静脉内脂肪组织来源的干细胞(ADSC)移植对大鼠嗅神经切断后嗅上皮再生的影响。研究设计:这是一项使用原代培养的动物脂肪组织来源的间充质干细胞的实验研究,并对动物嗅组织进行组织学分析。所有大鼠均行单侧嗅神经切断术,诱导嗅上皮变性,然后按时间顺序观察再生情况。从大鼠颈部脂肪组织中分离培养脂肪干细胞,并将其注射入实验组。对照组注射磷酸盐缓冲液,不注射脂肪干细胞。30天后,用嗅标记蛋白(OMP)和增殖细胞核抗原观察嗅上皮的再生。结果:嗅神经切断后5 d,嗅神经细胞消失,10 ~ 15 d,嗅神经细胞逐渐恢复正常厚度,细胞数量逐渐增多。到横断后30天,上皮的厚度和细胞组成几乎恢复到横断前的基线水平。然而,OMP表达与第0或3天相比仍然降低。将全身注射的ADSC移植到嗅上皮中并存活超过4周。ADSC在动物模型中促进嗅上皮的再生,并分化为嗅觉受体神经元和内皮细胞。结论:我们的研究结果表明,ADSC移植作为治疗头部创伤相关的嗅觉功能障碍的可行性。
Objective/Hypothesis: The purpose of the study was to investigate the effect of intravenous adipose tissue-derived stem cell (ADSC) transplantation on olfactory epithelium regeneration following transection of the olfactory nerve in rats.Study Design: This was a experimental study using primary cultures of mesenchymal stem cells derived from animal adipose tissue with histological analysis of animal olfactory tissue.Methods: All rats underwent unilateral transection of the olfactory nerve to induce degeneration of olfactory epithelium, and then were observed for regeneration according to time sequences. ADSCs were cultivated from neck adipose tissue of rats, and systemically injected into the experimental group. The control group was injected with phosphate buffered solution, instead of ADSCs. After 30 days, regeneration of olfactory epithelium was observed with olfactory marker protein (OMP) and proliferating cell nuclear antigen. To observe the characteristics of the transplanted ADSCs, olfactory epithelium was stained with von Willebrant factor and OMP.Results: After olfactory nerve transection, mature olfactory cells disappeared in 5 days, but gradually regained their thickness with increased cell numbers at approximately 10 to 15 days. By 30 days post-transection, the thickness and cellular composition of epithelium was almost restored to baseline levels pretransection. However, OMP expressions remained decreased compared with day 0 or 3. Systemically injected ADSCs were transplanted into the olfactory epithelium and survived beyond 4 weeks. The ADSCs promoted regeneration of olfactory epithelium in the animal model and differentiated into olfactory receptor neurons and endothelial cells.Conclusions: Our findings suggest the feasibility of ADSC transplantation as a treatment for head trauma-related olfactory dysfunction.