Guinea pigs as a model of in utero stem cell therapy for spina bifida

摘要 脊柱裂是美国儿童终生瘫痪最常见的原因。 各州。SB是由于第四周神经管未完全闭合所致。 怀孕了。暴露的脊髓承受着宫内化学和机械创伤， 导致儿童终生瘫痪，大小便失禁，肌肉骨骼 畸形和认知障碍。这些残疾需要广泛的医疗护理和 正在进行的身体和认知康复，使某人成为最昂贵的童年之一 疾病。最近的研究--包括我们自己的研究--表明，胎儿干预与 干细胞或其他技术有可能改善先天感染儿童的预后。 这种毁灭性的疾病。虽然医学和科学界从未像现在这样好过 定位于为某人开发新的开创性疗法，该领域缺乏 合适的动物模型。为了准确地模拟某人，动物必须有很长的孕期，耐受性 对胎儿的外科操作，并在出生时充分发育，以允许 运动功能评估。常用的SB动物模型包括大鼠、兔、 还有绵羊。到目前为止，小动物模型在很大程度上不适合开发 新的治疗方法；由于它们体积小，妊娠时间短，所以对胎儿进行外科手术 不能在胎龄足够早的时候进行，以准确地模拟人类SB。 此外，无法从这些模型中收集功能运动数据，因为大鼠和大鼠 兔子出生时也不会走动。虽然大型动物模型的怀孕时间更长， 更适合于胎儿操纵，而且出生后不久就可以走动，它们是 令人望而却步的昂贵和劳动密集型。从统计学上为绵羊研究的一只手臂提供动力 花费远远超过10万美元，可以花费一个外科医生和兽医团队整整一年的时间来 完成。 我们建议开发一种高通量、成本效益高的SB小动物模型 豚鼠。豚鼠有一种自然历史，这使该物种特别适合某人 子宫治疗研究。在所有常用的小鼠中，豚鼠的妊娠期最长 动物模型，比大鼠长三倍，比兔子长两倍。此外，几内亚 猪是唯一常用的能够行走和行走的小动物模型 出生时独立喂养。我们建议用豚鼠来开发一种可复制的小 某人的动物模型，将使调查人员能够快速和经济地评估 宫内新疗法的有效性。

Abstract Spina bifida (SB) is the most common cause of lifelong childhood paralysis in the United States. SB results from the incomplete closure of the neural tube during the fourth week of gestation. The exposed spinal cord sustains intrauterine chemical and mechanical trauma, leaving children with lifelong paralysis, bowel and bladder incontinence, musculoskeletal deformities, and cognitive disabilities. These disabilities require extensive medical care and ongoing physical and cognitive rehabilitation, making SB one of the most costly childhood diseases. Recent studies – including our own – have suggested that fetal interventions with stem cells or other techniques have the potential to improve the prognosis of children born with this devastating disease. While the medical and scientific community has never been better positioned to develop new groundbreaking therapies for SB, the field suffers from a lack of suitable animal models. To accurately model SB, animals must have a long gestation, tolerate surgical manipulation of the fetus, and be sufficiently developed at birth to allow for the assessment of locomotor function. Commonly used animal models of SB include rats, rabbits, and sheep. To date, small animal models have been largely unsuitable for the development of new therapies; due to their small size and short gestation surgical manipulation of the fetus cannot be performed at an early enough gestational age to accurately model human SB. Furthermore, functional locomotor data cannot be collected from these models as neither rats nor rabbits are ambulatory at birth. While large animal models have longer gestational times, are more suited for fetal manipulation, and are ambulatory shortly after birth, they are prohibitively expensive and labor intensive. To statistically power a single arm of a sheep study will cost well over $100,000 and can take a team of surgeons and veterinarians an entire year to complete. We propose to develop a high-throughput, cost effective small animal model of SB using guinea pigs. Guinea pigs have a natural history that makes the species uniquely suited for SB in utero treatment research. Guinea pigs have the longest gestation of any commonly used small animal models, three times as long as rats and twice as long as rabbits. Additionally, guinea pigs represent the only commonly used small animal model capable of ambulation and independent feeding at birth. We propose to use guinea pigs to develop a reproducible small animal model of SB that will allow investigators to quickly and economically assess the effectiveness of new in utero therapies.