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脂肪间充质干细胞片的植入促进了脊髓损伤后的轴突再生和膀胱功能的恢复。

Implantation of adipose-derived mesenchymal stem cell sheets promotes axonal regeneration and restores bladder function after spinal cord injury.

机构信息

Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Eastern Institute of Urologic Reconstruction, Shanghai Jiao Tong University, Shanghai, China.

Key Laboratory for Thin Film and Micro Fabrication of the Ministry of Education, School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Stem Cell Res Ther. 2022 Oct 12;13(1):503. doi: 10.1186/s13287-022-03188-1.

DOI:10.1186/s13287-022-03188-1
PMID:36224621
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9558366/
Abstract

BACKGROUND: Cell-based therapy using adipose-derived mesenchymal stem cells (ADSCs) is a promising treatment strategy for neurogenic bladder (NB) associated with spinal cord injury (SCI). However, therapeutic efficacy is low because of inefficient cell delivery. Cell sheets improve the efficacy of cell transplantation. Therefore, this study was conducted to investigate the therapeutic efficacy of transplanting ADSC sheets into an SCI rat model and focused on the function and pathological changes of the bladder. METHODS: ADSC sheets were prepared from adipose tissue of Sprague-Dawley (SD) rats using temperature-responsive cell culture dishes. Adult female SD rats were subjected to SCI by transection at the T10 level and administered ADSC sheets or gelatin sponge (the control group). Four and 8 weeks later, in vivo cystometrograms were obtained for voiding function assessment. Rats were sacrificed and the expression of various markers was analyzed in spinal and bladder tissues. RESULTS: The number of β-tubulin III-positive axons in the ADSC sheet transplantation group was higher than that in the control group. Conversely, expression of glial fibrillary acidic protein in the ADSC sheet transplantation group was lower than that in the control group. Cystometry showed impairment of the voiding function after SCI, which was improved after ADSC sheet transplantation with increased high-frequency oscillation activity. Furthermore, ADSC sheet transplantation prevented disruption of the bladder urothelium in SCI rats, thereby maintaining the intact barrier. Compared with fibrosis of the bladder wall in the control group, the ADSC sheet transplantation group had normal morphology of the bladder wall and reduced tissue fibrosis as shown by downregulation of type 1 collagen. ADSC sheet transplantation also resulted in strong upregulation of contractile smooth muscle cell (SMC) markers (α-smooth muscle actin and smoothelin) and downregulation of synthetic SMC markers (MYH10 and RBP1). CONCLUSION: ADSC sheet transplantation significantly improved voiding function recovery in rats after SCI. ADSC sheet transplantation is a promising cell delivery and treatment option for NB related to SCI.

摘要

背景：利用脂肪来源间充质干细胞（ADSCs）的细胞疗法是治疗与脊髓损伤（SCI）相关的神经源性膀胱（NB）的有前途的治疗策略。然而，由于细胞递送效率低下，治疗效果较低。细胞片提高了细胞移植的疗效。因此，本研究旨在探讨将 ADSC 片移植到 SCI 大鼠模型中的治疗效果，并重点研究膀胱的功能和病理变化。 方法：使用温度响应细胞培养皿从 Sprague-Dawley（SD）大鼠的脂肪组织中制备 ADSC 片。成年雌性 SD 大鼠通过 T10 水平横断接受 ADSC 片或明胶海绵（对照组）治疗。4 和 8 周后，进行体内尿动力学评估以获得排尿功能。处死大鼠，分析脊髓和膀胱组织中各种标志物的表达。 结果：ADSC 片移植组的β-微管蛋白 III 阳性轴突数量高于对照组。相反，ADSC 片移植组的神经胶质纤维酸性蛋白表达低于对照组。尿动力学检查显示 SCI 后排尿功能受损，ADSC 片移植后高频震荡活动增加，排尿功能得到改善。此外，ADSC 片移植可防止 SCI 大鼠膀胱尿路上皮破裂，从而维持完整的屏障。与对照组的膀胱壁纤维化相比，ADSC 片移植组的膀胱壁形态正常，组织纤维化减少，这表明 I 型胶原下调。ADSC 片移植还导致收缩性平滑肌细胞（SMC）标志物（α-平滑肌肌动蛋白和 smoothelin）的强烈上调和合成 SMC 标志物（MYH10 和 RBP1）的下调。 结论：ADSC 片移植可显著改善 SCI 后大鼠的排尿功能恢复。ADSC 片移植是治疗与 SCI 相关的 NB 的有前途的细胞输送和治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/fd1a9ca62a0b/13287_2022_3188_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/69d847401b4f/13287_2022_3188_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/dd6058b30632/13287_2022_3188_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/1d9572e6cc55/13287_2022_3188_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/a0a5b8d0d936/13287_2022_3188_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/fd4fa01c9dbe/13287_2022_3188_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/fd1a9ca62a0b/13287_2022_3188_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/69d847401b4f/13287_2022_3188_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/dd6058b30632/13287_2022_3188_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/1d9572e6cc55/13287_2022_3188_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/a0a5b8d0d936/13287_2022_3188_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/fd4fa01c9dbe/13287_2022_3188_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36c/9558366/fd1a9ca62a0b/13287_2022_3188_Fig6_HTML.jpg

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[5]
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[6]
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[7]
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[9]
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本文引用的文献

[1]
The Long-Term Efficacy Study of Multiple Allogeneic Canine Adipose Tissue-Derived Mesenchymal Stem Cells Transplantations Combined With Surgery in Four Dogs With Lumbosacral Spinal Cord Injury.

Cell Transplant. 2022

[2]
Inflammation and Barrier Function Deficits in the Bladder Urothelium of Patients with Chronic Spinal Cord Injury and Recurrent Urinary Tract Infections.

Biomedicines. 2022-1-20

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Regenerative Rehabilitation and Stem Cell Therapy Targeting Chronic Spinal Cord Injury: A Review of Preclinical Studies.

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Remodeling of extracellular matrix in the urinary bladder of paraplegic rats results in increased compliance and delayed fiber recruitment 16 weeks after spinal cord injury.

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World Neurosurg. 2022-3

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Treatment of spinal cord injury with mesenchymal stem cells.

Cell Biosci. 2020-9-22

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Neurourol Urodyn. 2020-11

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Physiol Rev. 2020-3-19

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