兽医学中的伴侣动物会发展出多种类似于人类疾病的自然发生的疾病。我们之前报告了对可行性的全面审查,安全,和使用新型干细胞疗法治疗狗和猫的各种炎症疾病的生物学活性(2008-2015)[1]。这篇综述的目的是提供伴侣动物疾病模型中当前研究的最新摘要,这些研究评估了与人类疾病相关的干细胞疗法。在这里,我们回顾了2015年至2023年在伴侣动物中评估的关于干细胞疗法的出版物的文献,包括狗,猫,和马。该综述排除了在实验诱导的疾病模型中进行的病例报告或研究,涉及癌症的研究,或在目的繁殖的实验室物种如啮齿动物中进行研究。我们确定了45份符合这些标准的手稿,从上一篇评论中描述的19个增加[1]。大多数研究在狗中进行(n=28),在马(n=9)和猫(n=8)中进行了其他研究。疾病模型包括与肌肉骨骼疾病相关的模型(骨关节炎,肌腱/韧带损伤),神经系统疾病(犬认知功能障碍,椎间盘疾病,脊髓损伤)牙龈/牙齿疾病(牙龈炎),皮肤病(特应性皮炎),慢性多药耐药感染,眼科疾病(干燥性角膜结膜炎,嗜酸性角膜炎,免疫介导的角膜炎),心肺疾病(哮喘,退行性瓣膜疾病,扩张型心肌病),胃肠道疾病(炎症性肠病,慢性肠病)和肾脏疾病(慢性肾脏疾病)。大多数研究报告了干细胞治疗的有益反应,除了那些与更慢性的过程,如脊髓损伤和慢性肾脏疾病。然而,还应该指出的是,22项研究是开放标签的,基线对照试验,只有12项研究是随机和对照的,使整体研究解释变得困难。如上次审查所述,在干细胞疗法的制造过程中,需要改善监管监督和一致性。使用先进的组学方法增强对疾病过程的时间过程的理解可以进一步告知作用机制并帮助定义适当的干预时机。基于干细胞的治疗的未来方向可能包括使用干细胞衍生的细胞外囊泡,或细胞调节方法,将细胞引导到适合个体疾病过程和疾病阶段的特定途径。
Companion animals in veterinary medicine develop multiple naturally occurring diseases analogous to human conditions. We previously reported a comprehensive review on the feasibility, safety, and biologic activity of using novel stem cell therapies to treat a variety of inflammatory conditions in dogs and cats (2008-2015) [Hoffman AM, Dow SW. Concise review: stem cell trials using companion animal disease models. Stem Cells. 2016;34(7):1709-1729. https://doi.org/10.1002/stem.2377]. The purpose of this review is to provide an updated summary of current studies in companion animal disease models that have evaluated stem cell therapeutics that are relevant to human disease. Here we have reviewed the literature from 2015 to 2023 for publications on stem cell therapies that have been evaluated in companion animals, including dogs, cats, and horses. The review excluded case reports or studies performed in experimentally induced models of disease, studies involving cancer, or studies in purpose-bred laboratory species such as rodents. We identified 45 manuscripts meeting these criteria, an increase from 19 that were described in the previous review [Hoffman AM, Dow SW. Concise review: stem cell trials using companion animal disease models. Stem Cells. 2016;34(7):1709-1729. https://doi.org/10.1002/stem.2377]. The majority of studies were performed in dogs (n = 28), with additional studies in horses (n = 9) and cats (n = 8). Disease models included those related to musculoskeletal disease (osteoarthritis and tendon/ligament injury), neurologic disease (canine cognitive dysfunction, intervertebral disc disease, spinal cord injury) gingival/dental disease (gingivostomatitis), dermatologic disease (atopic dermatitis), chronic multi-drug resistant infections, ophthalmic disease (keratoconjunctivitis sicca, eosinophilic keratitis, immune-mediated keratitis), cardiopulmonary disease (asthma, degenerative valve disease, dilated cardiomyopathy), gastrointestinal disease (inflammatory bowel disease, chronic enteropathy), and renal disease (chronic kidney disease). The majority of studies reported beneficial responses to stem cell treatment, with the exception of those related to more chronic processes such as spinal cord injury and chronic kidney disease. However, it should also be noted that 22 studies were open-label, baseline-controlled trials and only 12 studies were randomized and controlled, making overall study interpretation difficult. As noted in the previous review, improved regulatory oversight and consistency in manufacturing of stem cell therapies are needed. Enhanced understanding of the temporal course of disease processes using advanced-omics approaches may further inform mechanisms of action and help define appropriate timing of interventions. Future directions of stem-cell-based therapies could include use of stem-cell-derived extracellular vesicles, or cell conditioning approaches to direct cells to specific pathways that are tailored to individual disease processes and stages of illness.