Comparison of the therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells and adipose-derived stem cells on erectile dysfunction in a rat model of bilateral cavernous nerve injury.
Comparison of the therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells and adipose-derived stem cells on erectile dysfunction in a rat model of bilateral cavernous nerve injury.
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DOI：
10.3389/fbioe.2022.1019063
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发表时间：
2022
影响因子：
5.7
通讯作者：
Lu, Mujun
中科院分区：
文献类型：
--
作者：
Ti, Yunrong;Yang, Mengbo;Chen, Xinda;Zhang, Ming;Xia, Jingjing;Lv, Xiangguo;Xiao, Dongdong;Wang, Jiucun;Lu, Mujun
关键词：
背景：海绵体神经损伤（CNI）是骨盆骨折和根治性切除术后勃起功能障碍（艾德）的主要原因。移植人脂肪干细胞（ASC）已被广泛用于恢复CNI-ED大鼠和患者的勃起功能。脐带血来源的间充质干细胞（CBMSCs）同样具有低免疫原性，但与ASC相比更为原始，并且由于脐带血库的广泛建立，在大规模商业应用中更有前途。然而，CBMSCs和ASCs是否对CNI-ED具有不同的治疗效果以及潜在的机制仍然不清楚。 材料与方法：采用双侧海绵体神经夹伤法建立大鼠双侧海绵体神经损伤（BCNI）模型。破碎后，立即将ASCs和CBMSCs注射到海绵体内。在4周和12周时评估阴茎组织的勃起功能、Masson染色和免疫荧光分析。阴茎海绵体内注射PKH-26标记的ASC或CBMSC，以确定注射后3天阴茎中ASC或CBMSC的存在和分化。体外实验包括细胞内活性氧检测、线粒体膜电位测定、EdU细胞增殖染色、细胞凋亡测定和蛋白质芯片分析，以探讨CBMSC处理与ASC处理相比的潜在机制。 结果如下：CBMSC注射显著恢复了勃起功能，挽救了海绵体平滑肌的损失，并增加了平滑肌与胶原蛋白的比例。PKH-26标记的CBMSCs或ASCs不与海绵体中的内皮细胞或平滑肌细胞共定位。CBMSCs条件培养液能显著抑制雪旺细胞氧化应激，提高线粒体膜电位，促进细胞增殖。无论在体内还是体外，CBMSC组的治疗效果均优于ASC组。CBMSC-CM中神经营养因子和基质金属蛋白酶的含量明显高于ASC-CM，尤其是NT 4、VEGF、MMP 1和MMP 3的含量明显高于ASC-CM。 结论：海绵体内注射CBMSCs较ASCs能更好地恢复CNI-ED大鼠的勃起功能，其原因是CBMSCs分泌的因子丰富，能促进神经再生，减少细胞外基质沉积。CBMSC移植治疗CNI-ED是一种很有前途的治疗方法。
Background: Cavernous nerve injury (CNI) is the leading cause of erectile dysfunction (ED) after radical prostatectomy and pelvic fracture. Transplantation of human adipose-derived stem cells (ASCs) has been widely used to restore erectile function in CNI-ED rats and patients. Umbilical cord blood-derived MSCs (CBMSCs) are similarly low immunogenic but much primitive compared to ASCs and more promising in large-scale commercial applications due to the extensive establishment of cord blood banks. However, whether CBMSCs and ASCs have differential therapeutic efficacy on CNI-ED and the underlying mechanisms are still not clear. Materials and methods: A bilateral cavernous nerve injury (BCNI) rat model was established by crushing the bilateral cavernous nerves. After crushing, ASCs and CBMSCs were intracavernously injected immediately. Erectile function, Masson staining, and immunofluorescence analyses of penile tissues were assessed at 4 and 12 weeks. PKH-26-labeled ASCs or CBMSCs were intracavernously injected to determine the presence and differentiation of ASCs or CBMSCs in the penis 3 days after injection. In vitro experiments including intracellular ROS detection, mitochondrial membrane potential assay, EdU cell proliferation staining, cell apoptosis assay, and protein chip assay were conducted to explore the underlying mechanism of CBMSC treatment compared with ASC treatment. Results: CBMSC injection significantly restored erectile function, rescued the loss of cavernous corporal smooth muscles, and increased the ratio of smooth muscle to collagen. PKH-26-labeled CBMSCs or ASCs did not colocalize with endothelial cells or smooth muscle cells in the corpus cavernosum. Moreover, the conditioned medium (CM) of CBMSCs could significantly inhibit the oxidative stress and elevate the mitochondria membrane potential and proliferation of Schwann cells. Better therapeutic effects were observed in the CBMSC group than the ASC group both in vivo and in vitro. In addition, the content of neurotrophic factors and matrix metalloproteinases in CBMSC-CM, especially NT4, VEGF, MMP1, and MMP3 was significantly higher than that of ASC-CM. Conclusion: Intracavernous injection of CBMSCs exhibited a better erectile function restoration than that of ASCs in CNI-ED rats owing to richer secretory factors, which can promote nerve regeneration and reduce extracellular matrix deposition. CBMSC transplantation would be a promising therapeutic strategy for CNI-ED regeneration in the future.
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影响因子：
8.9
作者：
Inman BA;Sauver JL;Jacobson DJ;McGree ME;Nehra A;Lieber MM;Roger VL;Jacobsen SJ
通讯作者：
Jacobsen SJ
DOI：
10.1111/j.1743-6109.2008.01190.x
发表时间：
2009-03
期刊：
The journal of sexual medicine
影响因子：
--
作者：
Lin G;Banie L;Ning H;Bella AJ;Lin CS;Lue TF
通讯作者：
Lue TF
影响因子：
4.2
作者：
Hannan, Johanna L.;Albersen, Maarten;Stopak, Bernard L.;Liu, Xiaopu;Burnett, Arthur L.;Hoke, Ahmet;Bivalacqua, Trinity J.
通讯作者：
Bivalacqua, Trinity J.
DOI：
10.1016/j.bbrc.2014.01.084
发表时间：
2014-02-28
影响因子：
3.1
作者：
Eom, Young Woo;Oh, Ji-Eun;Shim, Kwang Yong
通讯作者：
Shim, Kwang Yong
影响因子：
5.2
作者：
Lunn, J. Simon;Sakowski, Stacey A.;Feldman, Eva L.
通讯作者：
Feldman, Eva L.