Abstract：
OBJECTIVE: 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.
METHODS: 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 × 105 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.
RESULTS: 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.
CONCLUSIONS: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.
METHODS: 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 × 105 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.
RESULTS: 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.
CONCLUSIONS: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.
摘要：
目的：评估静脉内给予人多分化应激持久（Muse）细胞对无免疫抑制剂的海绵状神经（CN）损伤的大鼠术后勃起功能障碍（ED）的影响。
方法：将雄性SD大鼠随机分为3组。无论是人类缪斯细胞，非Muse间充质干细胞（MSCs）（均为1.0×105细胞），在没有免疫抑制剂的情况下，在CN损伤后3小时静脉输注或媒介物。在手术后28天的骨盆神经电刺激期间，通过测量海绵体内压（ICP）和动脉压（AP）来评估勃起功能。在静脉输注Muse细胞后48小时和28天，在CN损伤后的主要骨盆神经节（MPG）中评估了Muse细胞和非MuseMSCs的归巢。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）和神经胶质细胞系源性神经营养因子（Gdnf）的表达。使用单向方差分析，然后对参数数据进行Tukey检验，对非参数数据进行KruskalWallis检验，然后进行Dunn-Bonferroni检验。
结果：Muse细胞组28天的平均ICP/AP值为0.51±0.02，非MuseMSC组0.37±0.03，载体组0.36±0.04，与非Muse和媒介物组相比,Muse细胞组中显示出显著的阳性反应(分别为P=0.013和0.010)。在MPG中，观察到Muse细胞在48小时移植，并在28天表达施万细胞标志物S100（〜46％）和GFAP（〜24％），而非MuseMSCs在48小时时基本上不移植。在输注后48小时,Muse组的MPG中识别出Cxcl12(P=0.048)和Gdnf(P=0.040)的更高基因表达。
结论：在大鼠模型中，静脉移植的人Muse细胞在CN损伤后恢复了大鼠的勃起功能，可能是通过上调Cxcl12和Gdnf。
方法：将雄性SD大鼠随机分为3组。无论是人类缪斯细胞，非Muse间充质干细胞（MSCs）（均为1.0×105细胞），在没有免疫抑制剂的情况下，在CN损伤后3小时静脉输注或媒介物。在手术后28天的骨盆神经电刺激期间，通过测量海绵体内压（ICP）和动脉压（AP）来评估勃起功能。在静脉输注Muse细胞后48小时和28天，在CN损伤后的主要骨盆神经节（MPG）中评估了Muse细胞和非MuseMSCs的归巢。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）和神经胶质细胞系源性神经营养因子（Gdnf）的表达。使用单向方差分析，然后对参数数据进行Tukey检验，对非参数数据进行KruskalWallis检验，然后进行Dunn-Bonferroni检验。
结果：Muse细胞组28天的平均ICP/AP值为0.51±0.02，非MuseMSC组0.37±0.03，载体组0.36±0.04，与非Muse和媒介物组相比,Muse细胞组中显示出显著的阳性反应(分别为P=0.013和0.010)。在MPG中，观察到Muse细胞在48小时移植，并在28天表达施万细胞标志物S100（〜46％）和GFAP（〜24％），而非MuseMSCs在48小时时基本上不移植。在输注后48小时,Muse组的MPG中识别出Cxcl12(P=0.048)和Gdnf(P=0.040)的更高基因表达。
结论：在大鼠模型中，静脉移植的人Muse细胞在CN损伤后恢复了大鼠的勃起功能，可能是通过上调Cxcl12和Gdnf。
