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發表人 | 討論主題 | 發表時間 | 討論數 |
李宏耕 | 使用脂肪組織血管基質組分治療大鼠部分膀胱出口阻塞誘導之膀胱低下症的效果 | 2022/7/10 下午 08:59:27 | 0 |
原 文 | 題 目 | Therapeutic effect of adipose stromal vascular fraction spheroids for partial bladder outlet obstruction induced underactive bladder |
作 者 | Jingyu Liu, Liuhua Zhou, Feng Zhao, Changcheng Zhou, Tianli Yang, Zhongle Xu, Xinning Wang, Luwei Xu, Zheng Xu, Yuzheng Ge, Ran Wu & Ruipeng Jia | |
出 處 | Stem Cell Res Ther. 2022 Feb 9;13(1):68. doi: 10.1186/s13287-022-02739-w. | |
出版日期 | 2022/2/9 | |
評 論 |
『膀胱低下症』(underactive bladder) 是泌尿科門診常見而棘手的問題。如同人們耳熟能詳的『膀胱過動症』(overactive bladder),膀胱低下症是一種症候群,國際尿失禁學會(ICS)定義為A symptom complex characterized by a slow urinary stream(小便無力)、hesitancy(等一下才能尿出來)、 and straining to void(小便費力)、with or without a feeling of incomplete bladder emptying(尿不乾淨)、sometimes with storage symptoms(頻尿,急尿,夜尿),可見其主要的表現是小便不好排出。臨床上我們會安排尿路動力學檢查,而其表現為膀胱逼尿肌力量低下(detrusor underactivity)。膀胱低下症可能的成因很多,老化,神經方面疾病如腦血管疾患,巴金森氏症,脊椎損傷等,肌肉方面疾病如膀胱出口阻塞,糖尿病等,或醫源性疾患如根除性骨盆腔器官手術後,都是可能的致病因子。目前對於UAB治療,目前(2022年)EAU準則建議自我導尿(CIC)或在保守治療無效的女性提供sacral nerve stimulation,並沒有其他強烈推薦的選擇。 Stromal vascular fraction(SVF)是將脂肪細胞離心後取沉澱的pellet做應用。其中含有endothelial cells,smooth muscle cells, fibroblasts, blood cells, and mesenchymal cells。 因此,SVF具備self-renewing,differentiation, and secrete growth factors 的潛力。Spheroid中文翻譯為球體,其利用特殊立體培養的技術,使培養脂肪細胞有類似在活體內的立體架構,脂肪細胞距離血管較近,能更容易得到養分,氧氣,growth factors等,增進其生理功能。已有文獻探討SVF spheroid(SVFsp)對於心臟缺血相關試驗,而作者則是用SVF/SVFsp 治療UAB大鼠,評估其對於UAB的療效。 作者選用SD rat,利用partial bladder outlet obstruction model,將大鼠分成sham、SVF、and SVFsp三組,在膀胱的前後左右壁分別打入buffer solution、adipose(AD)-SVF、AD-SVFsp觀察測量growth factors分泌量,血管新生的長度,注射的細胞停留在膀胱壁的時間,以及膀胱生理功能恢復的情況。作者發現SVFsp相較於SVF,能分泌更多的growth factors,更強的angiogenecity,能停留在膀胱壁的時間更久,增加膀胱收縮力,並更能減少殘尿。據作者研究,AD-SVFsp的作用,或許與活化與cell survival相關的AKT/GSK-3β pathway有關。作者提到研究的limitation包含只選用BOO model,仍需探討其他UAB成因如DM等model是否能使用SVF治療,且觀察時間為一個月,需要更多研究評估其長期效果。 本篇作者使用SVFsp治療BOO引發的UAB,或許有潛力成為我們面對這難解之題提供病患治療的選擇,然而,本篇如果能比較AD-SVFsp治療後與control(完全沒有接受任何手術等治療)的大鼠其功能間比較,或許更能彰顯SVFsp療效。未來若能應用在人類身上,或許可以探討combination 藥物或手術的療效,或許能更勝於單純SVFsp治療。雖然從實驗室到臨床應用還有很長的路,但SVF治療還是帶給UAB這領域一個新的方向。 |
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abstract |
Background: Underactive bladder (UAB) is a common clinical problem but related research is rarely explored. As there are currently no effective therapies, the administration of adipose stromal vascular fraction (ad-SVF) provides a new potential method to treat underactive bladder. Methods: Male Sprague–Dawley rats were induced by partial bladder outlet obstruction (PBOO) for four weeks and randomly divided into three groups: rats treated with PBS (Sham group); rats administrated with ad-SVF (ad-SVF group) and rats performed with ad-SVF spheroids (ad-SVFsp group). After four weeks, urodynamic studies were performed to evaluate bladder functions and all rats were sacrificed for further studies. Results: We observed that the bladder functions and symptoms of UAB were significantly improved in the ad-SVFsp group than that in the Sham group and ad-SVF group. Meanwhile, our data showed that ad-SVF spheroids could remarkably promote angiogenesis, suppress cell apoptosis and stimulate cell proliferation in bladder tissue than that in the other two groups. Moreover, ad-SVF spheroids increased the expression levels of bFGF, HGF and VEGF-A than ad-SVF. IVIS Spectrum small-animal in vivo imaging system revealed that ad-SVF spheroids could increase the retention rate of transplanted cells in bladder tissue. Conclusions: Ad-SVF spheroids improved functions and symptoms of bladder induced by PBOO, which contributes to promote angiogenesis, suppress cell apoptosis and stimulate cell proliferation. Ad-SVF spheroids provide a potential treatment for the future patients with UAB. Keywords: Stromal vascular fraction, Spheroid, Bladder outlet obstruction, Underactive bladder |
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