Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
BJU Int. 2024 Mar;133(3):332-340. doi: 10.1111/bju.16232. Epub 2023 Dec 11.
To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant.
Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 10 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data.
The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (46%) and glial fibrillary acidic protein (24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion.
Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.
评估静脉注射人多谱系分化应激耐受（Muse）细胞对无免疫抑制剂的 cavernous 神经（CN）损伤大鼠术后勃起功能障碍（ED）的影响。
雄性 Sprague-Dawley 大鼠在 CN 挤压伤后随机分为三组。在 CN 损伤后 3 小时，分别静脉注射人-Muse 细胞、非-Muse 间充质干细胞（MSCs）（均为 1.0×106 个细胞）或载体，无免疫抑制剂。术后 28 天，通过测量骨盆神经电刺激时的海绵体内压（ICP）和动脉压（AP）来评估勃起功能。静脉输注 Muse 细胞后 48 小时和 28 天，评估 Muse 细胞和非-Muse MSCs 在 CN 损伤后的主要骨盆神经节（MPG）中的归巢情况。此外，通过实时聚合酶链反应检测 MPG 中 C-X-C 基序趋化因子配体（Cxcl12）和胶质细胞源性神经营养因子（Gdnf）的表达。使用单因素方差分析（ANOVA）对组间进行统计分析和比较，然后使用 Tukey 检验进行参数数据比较，使用 Kruskal-Wallis 检验进行非参数数据比较。
Muse 细胞组 28 天时的平均（SEM）ICP/AP 值为 0.51（0.02），非-Muse MSC 组为 0.37（0.03），载体组为 0.36（0.04），Muse 细胞组与非-Muse 和载体组相比，勃起反应明显增强（P=0.013 和 P=0.010）。在 MPG 中，在 48 小时时观察到 Muse 细胞被移植，在 28 天时表达 Schwann 细胞标志物 S100（46%）和胶质纤维酸性蛋白（24%），而在 48 小时时基本未观察到非-Muse MSCs 被移植。在 Muse 组，与载体组相比，静脉注射后 48 小时，MPG 中 Cxcl12（P=0.048）和 Gdnf（P=0.040）的基因表达水平更高。
静脉移植的人 Muse 细胞通过上调 Cxcl12 和 Gdnf，可能恢复大鼠 CN 损伤后的勃起功能。
