Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency.
Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency.
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DOI：
10.1186/s13287-016-0461-6
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发表时间：
2017-01-06
影响因子：
7.5
通讯作者：
Andersson KE
中科院分区：
文献类型：
--
作者：
Williams JK;Dean A;Lankford S;Criswell T;Badlani G;Andersson KE
细胞疗法对女性内源性尿道括约肌缺陷（ISD）的疗效中等，需要改进。为了提高治疗效果，重要的是更好地了解不同患者队列中细胞功效的决定因素。我们已经报道，在非人灵长类动物中，ISD的慢性化可能会影响细胞功效，但其他因素（年龄，心理社会压力，激素状态，体重）可能与女性的许多疾病/治疗结果相关-这些因素是本研究的重点。将成年雌性食蟹猴分组：（1）年轻（n = 10，5-8岁）与老年（n = 10，13-18岁）;（2）年龄匹配/社会从属（n = 15）与社会主导（n = 15）;和（3）年龄匹配较低体重（n = 6）与较高体重（n = 6）。自体骨骼肌前体细胞（skMPCs，500万）注射到尿道括约肌6周后，手术诱导ISD程序。在skMPC治疗前、治疗后3个月和6个月测量静息和阴部神经刺激的最大尿道压力（MUP），并在治疗后6个月通过定量组织学测量括约肌复合体内的尿道括约肌/胶原蛋白含量。skMPC对MUP和括约肌/胶原蛋白比率的功效受年龄（功效平均降低40%，p < 0.05 vs.年轻NHP）、社会压力（功效平均降低30%，p < 0.05 vs.社会主导）和体重/空腹葡萄糖浓度（功效平均降低35%，p < 0.05 vs.较低体重）的影响。多种因素（年龄、应激诱发的痛经和体重）影响细胞治疗恢复患有ISD的NHP患者尿道括约肌复合体结构和功能的疗效。应考虑这些患者队列的考虑和替代方案。
Cell therapy for intrinsic urinary sphincter deficiency (ISD) in women has been moderately effective, and improvements are needed. To improve treatment efficacy, it is important to better understand determinates of cell efficacy in the different patient cohorts. We have reported that in nonhuman primates the chronicity of ISD may affect cell efficacy, but additional factors (age, psychosocial stress, hormone status, body weight) can be associated with many disease/treatment outcomes in women – and these factors are the focus of this study. Adult female cynomolgus monkeys were divided into groups: (1) younger (n = 10, 5–8 years of age) versus older (n = 10, 13–18 years of age); (2) age-matched/socially subordinate (n = 15) versus socially dominant (n = 15); and (3) age-matched lower body weight (n = 6) versus higher body weight (n = 6). Autologous skeletal muscle precursor cells (skMPCs, 5 million) were injected into the urinary sphincter 6 weeks after a surgically induced ISD procedure. Resting and pudendal nerve-stimulated maximal urethral pressures (MUP) were measured before, and 3 and 6 months post-skMPC treatment and urinary sphincter muscle/collagen content within the sphincter complex was measured by quantitative histology 6 months posttreatment. Efficacy of skMPCs on MUP and sphincter muscle/collagen ratios are affected by age (average 40% reduction in efficacy, p < 0.05 vs. younger NHPs), social stress (average 30% reduction in efficacy, p < 0.05 vs. socially dominant) and body weight/fasting glucose concentrations (average 35% reduction in efficacy, p < 0.05 vs. lower body weight). Multiple factors (age, stress-induced dysmenorrhea, and body weight) affect the efficacy of cell therapy to restore structure and function in the urinary sphincter complex in NHPs with ISD. Consideration of, and alternatives for, these patient cohorts should be considered.
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DOI：
10.1016/s0002-9378(89)80013-4
发表时间：
1989-05-01
影响因子：
9.8
作者：
CLARKSON, TB;ADAMS, MR;KORITNIK, DR
通讯作者：
KORITNIK, DR
影响因子：
7.5
作者：
Williams, J. Koudy;Badlani, Gopal;Andersson, Karl-Erik
通讯作者：
Andersson, Karl-Erik
影响因子：
4
作者：
Koopman R;Ly CH;Ryall JG
通讯作者：
Ryall JG
影响因子：
4
作者：
Katsara, Olga;Mahaira, Louisa G.;Perez, Sonia A.
通讯作者：
Perez, Sonia A.
影响因子：
--
作者：
Jiang, Hai-Hong;Damaser, Margot S
通讯作者：
Damaser, Margot S