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脂肪组织来源的间充质干细胞和富含血小板血浆在治疗慢性马肢蹄病中的作用:概念验证。

The Contribution of Adipose Tissue-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma to the Treatment of Chronic Equine Laminitis: A Proof of Concept.

机构信息

Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy.

Veterinary Practitioner, Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy.

出版信息

Int J Mol Sci. 2017 Oct 11;18(10):2122. doi: 10.3390/ijms18102122.

Abstract

Laminitis, a highly debilitating disease of the foot in ungulates, is characterized by pathological changes of the complex lamellar structures that maintain the appendicular skeleton within the hoof. Laminitis is a multifactorial disease that involves perturbation of the vascular, hematological, and inflammatory homeostasis of the foot. Interestingly, the pathogenesis of the disease resembles what is observed in metabolic syndromes and sepsis-induced organ failure in humans and animals. We hypothesized that local administration of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) might contribute to establishing an anti-inflammatory and pro-angiogenic environment, and could stimulate the injured tissue in order to restore its functional integrity. According to this assumption, an experimental protocol based on the local intravenous administration of adipose tissue-derived MSCs (aMSCs) in combination with PRP was developed for the treatment of horses affected by chronic laminitis. Nine horses with severely compromised venograms (showing grade III and IV laminitis) that had been unsuccessfully treated with conventional therapies were enrolled. aMSCs and PRP (15 × 10⁶ cells resuspended in 15 mL of PRP) were injected into the lateral or medial digital vein three times, at one-month intervals. The first administration was performed with allogeneic aMSCs, while for the following administrations, autologous aMSCs were used. There was no adverse short-term reaction to the intravenous injection of aMSCs. In the long term, venograms outlined, in all subjects, a progressive amelioration of the vascularization of the foot. An improvement in the structure and function of the hoof was also observed. No adverse events were reported during the follow-up, and the horses returned to a comfortable quality of life. Although the number of animals enrolled in the study is limited, both clinical observations and venography demonstrated an enhancement in the condition of all horses, suggesting that the regenerative therapies in chronic laminitis could be useful, and are worthy of further investigation.

摘要

蹄叶炎是一种严重的蹄部疾病,其特征是维持附肢骨骼在蹄中的复杂板层结构发生病理性变化。蹄叶炎是一种多因素疾病,涉及到足部血管、血液和炎症的稳态紊乱。有趣的是,这种疾病的发病机制类似于人类和动物代谢综合征和脓毒症引起的器官衰竭。我们假设,间充质干细胞(MSCs)和富含血小板的血浆(PRP)的局部给药可能有助于建立抗炎和促血管生成的环境,并刺激受损组织以恢复其功能完整性。根据这一假设,我们制定了一个基于脂肪组织来源的间充质干细胞(aMSCs)与 PRP 局部静脉内给药的实验方案,用于治疗患有慢性蹄叶炎的马匹。共招募了 9 匹患有严重静脉造影异常(表现为 III 级和 IV 级蹄叶炎)且经常规治疗无效的马。将 15 × 10⁶ 个细胞悬浮在 15 mL 的 PRP 中,aMSCs 和 PRP 分三次,每月一次,注入到侧或中趾静脉。第一次给药采用同种异体 aMSCs,随后的给药则采用自体 aMSCs。静脉内注射 aMSCs 没有引起短期不良反应。从长期来看,所有受试者的静脉造影均显示足部血管化逐渐改善。蹄的结构和功能也得到了改善。在随访期间没有报告不良事件,并且这些马恢复了舒适的生活质量。尽管该研究纳入的动物数量有限,但临床观察和静脉造影均显示所有马匹的病情均有改善,提示慢性蹄叶炎的再生疗法可能有用,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/250c/5666804/52fbb043b2da/ijms-18-02122-g001.jpg

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