Objective

Due to the immunomodulatory properties of mesenchymal stem cells (MSCs) through stimulation of endogenous immune cells by paracrine signals and cell contact, they have been proposed as alternative treatment option for many inflammatory and immune-mediated diseases in veterinary medicine. However, the long-term cultivation possibilities of feline MSCs are currently compromised due to a restricted proliferation capacity. Therefore, the xenogeneic use of equine peripheral blood-derived MSCs (ePB-MSCs) would present an interesting alternative thanks to their superior cultivation properties. To the authors’ knowledge, there are currently no safety reports concerning the xenogeneic use of ePB-MSCs in cats. Therefore, the overall goal of this preliminary study was to investigate if ePB-MSCs can safely be administered in healthy cats and by extension evaluating their immunogenic and immunomodulatory properties.

Methods

Ten healthy cats were intravenously (i.v.) injected with 3 × 10⁵ ePB-MSCs at three time points (T₀, T₁, T₂). All cats were daily inspected by the caretaker and underwent a physical examination with hematological and biochemical analysis at day 0 (T₀), week 2 (T₁), week 4 (T₂) and week 6 (T₃) by a veterinarian. Furthermore, a modified mixed lymphocyte reaction (MLR) was performed at T₀ and T₃ for each cat in order to evaluate immunogenic and immunomodulatory properties of the ePB-MSCs

Results

No adverse clinical effects could be detected following repeated i.v. administration of ePB-MSCs in all cats. Significant lower protein (T₁: P-value = 0.002; T₂: P-value > 0.001; T₃: P-value = 0.004) and albumin levels (T₁: P-value = 0.003; T₂: P-value = 0.001) were seen after repeated administration of ePB-MSCs, compared to T₀. However, all biochemical and hematological parameters stayed within clinical acceptance level. In addition, the repeated injections did not induce a cellular immune response before and after repeated ePB-MSCs administration. Furthermore, convincing immunomodulatory properties of ePB-MSCs on feline peripheral blood mononuclear cells were confirmed in the MLR-assay

Conclusion

This preliminary study demonstrates that ePB-MSCs can safely be administered in healthy cats and provide a promising alternative for the treatment of various inflammatory diseases in cats.

中文翻译：

---

健康猫中马外周血间充质干细胞的安全性和免疫调节特性。

目的

由于间充质干细胞（MSCs）通过旁分泌信号和细胞接触刺激内源性免疫细胞而具有免疫调节特性，因此已被提议作为兽医学中许多炎症和免疫介导疾病的替代治疗选择。但是，由于增殖能力受到限制，猫MSC的长期培养可能性目前受到损害。因此，由于其优越的培养特性，异种使用马外周血来源的MSC（ePB-MSC）将是一个有趣的选择。据作者所知，目前尚无关于猫中ePB-MSC异种使用的安全性报告。因此，

方法

在三个时间点（T ₀，T ₁，T ₂）对10只健康的猫静脉（iv）注射3×10 ⁵ ePB-MSC 。每天由看守检查所有猫，并在第0天（T ₀），第2周（T ₁），第4周（T ₂）和第6周（T ₃）接受兽医的血液学和生化分析检查。此外，对每只猫在T ₀和T ₃进行了改良的混合淋巴细胞反应（MLR），以评估ePB-MSC的免疫原性和免疫调节特性

结果

在所有猫中重复静脉内施用ePB-MSC后，没有发现不良的临床作用。较低的蛋白质（T ₁：P值= 0.002; T ₂：P值> 0.001; T ₃：P值= 0.004）和白蛋白水平（T ₁：P值= 0.003; T ₂：P值）重复给药ePB-MSC后观察到= 0.001），与T ₀相比。但是，所有生化和血液学参数均保持在临床接受水平之内。另外，重复注射在重复施用ePB-MSC之前和之后均未诱导细胞免疫应答。此外，在MLR分析中证实了ePB-MSCs在猫外周血单核细胞上具有令人信服的免疫调节特性。

结论

这项初步研究表明，ePB-MSC可以在健康的猫中安全使用，并为猫的各种炎症性疾病的治疗提供了有希望的替代方法。