Local versus intravenous injections of skeletal muscle precursor cells in nonhuman primates with acute or chronic intrinsic urinary sphincter deficiency
Local versus intravenous injections of skeletal muscle precursor cells in nonhuman primates with acute or chronic intrinsic urinary sphincter deficiency
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DOI：
10.1186/s13287-016-0411-3
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发表时间：
2016-10-07
影响因子：
7.5
通讯作者：
Andersson, Karl-Erik
中科院分区：
文献类型：
--
作者：
Williams, J. Koudy;Badlani, Gopal;Andersson, Karl-Erik
背景资料：许多因素可能会影响细胞疗法治疗内源性尿道括约肌缺陷（ISD）的疗效，包括细胞的给药途径和括约肌的状况。本研究的目的是比较局部和静脉注射自体骨骼肌前体细胞（skMPCs）对患有急性或慢性ISD的非人灵长类动物（NHP）的作用。（n = 4/组）：（1）对照;（2）手术诱导的ISD/未治疗;（3）急性ISD（6周持续时间）/仅局部媒介物;（4）急性ISD/局部skMPC注射;（5）急性ISD/全身skMPC;（6）慢性ISD（6个月持续时间）/局部媒介物;（7）慢性ISD/局部skMPC;（8）慢性ISD/全身skMPC。在ISD前、治疗前和治疗后3个月和6个月测量最大尿道压力（MUP）。结果：在患有急性ISD的NHP中，全身和局部施用skMPC均增加静息MUP值和括约肌含量（p < 0.05 vs. ISD/载体）。但全身给药效果明显低于局部注射（p > 0.05）。在患有慢性ISD的NHP中，局部skMPC给药对MUP和括约肌值的影响降低（与患有急性ISD的NHP相比）（与急性ISD/skMPC相比，p < 0.05）;全身给药无影响。阴部神经刺激的MUP增加仅在局部skMPC治疗的急性ISD NHP中显著（p < 0.05，相对于静息MUP）。括约肌血管化和神经支配的程度直接关系到MUP和括约肌contents.Conclusions：慢性ISD和细胞注射的途径影响细胞治疗在猴模型ISD的疗效。这可能与这些不同治疗条件下细胞刺激血管形成和神经再支配的相对能力有关。
Background: Many factors may influence the efficacy of cell therapy for intrinsic urinary sphincter deficiency (ISD), including the route of administration of the cells and the condition of the sphincter. The goal of this study was to compare local versus intravenous administration of autologous skeletal muscle precursor cells (skMPCs) when administered to nonhuman primates (NHPs) with either acute or chronic ISD.Methods: Thirty-two adult female monkeys were divided into eight groups (n = 4/group): (1) control; (2) surgically induced ISD/no treatment; (3) acute ISD (6-week duration)/local vehicle only; (4) acute ISD/local skMPC injection; (5) acute ISD/systemic skMPC; (6) chronic ISD (6-month duration)/local vehicle; (7) chronic ISD/local skMPC; (8) chronic ISD/systemic skMPC. Maximal urethral pressures (MUP) were measured prior to ISD, prior to treatment and at 3 and 6 months following treatment. Quantitative histology was used to measure muscle/collagen content, somatic innervation, and vascularity of the sphincter complexes.Results: In NHPs with acute ISD both systemic and local administration of skMPCs increased resting MUP values and sphincter muscle content (p < 0.05 vs. ISD/vehicle). However, the effects of systemic skMPC administration were significantly lower than those of local injection (p > 0.05). In NHPs with chronic ISD local skMPC administration had reduced (compared to NHPs with acute ISD) effects on MUP and sphincter muscle values (p < 0.05 vs. acute ISD/skMPC); systemic administration had no effect. Pudendal nerve-stimulated increases in MUP were significant only in acute ISD NHPs with local skMPC treatment (p < 0.05 vs. resting MUP). The extent of sphincter vascularization and innervation were directly related to MUP and sphincter muscle content.Conclusions: Both the chronicity of ISD and the route of cell injection influence the efficacy of cell therapy in monkey models of ISD. This may be related to the relative ability of cells to stimulate vascularization and re-innervation in these different treatment conditions.