Preclinical Assessment of Safety and Efficacy of Deferoxamine (DFO)-pretreated Feline Adipose Mesenchymal Stem Cells.

IF 1.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

In vivo Pub Date : 2025-01-01 DOI:10.21873/invivo.13825

Hailong Teng, Minkyung Cho, Zhiqiang Ma, Xinpeng Ji, Shiyu Jin, Yuze Zhou, Meifu Xuan, Hyun-A Seong, Xiangzi Li, Seong-Ho Choi, Qiang Li

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引用次数: 0

Abstract

Background/aim: This study aimed to investigate the safety and efficacy of deferoxamine (DFO) pretreated feline adipose tissue derived mesenchymal stem cells (fATMSCs) for the treatment of inflammatory disorders.

Materials and methods: fATMSCs were isolated from feline adipose tissue and characterized using flow cytometry for surface marker expression and differentiation assays for adipogenic, osteogenic, and chondrogenic lineages. Different concentrations of DFO were used to evaluate its impact on fATMSC activity. The therapeutic potential of these preconditioned cells was validated using a mouse model of acute lung injury (ALI) by LPS injection. Comprehensive evaluations, including clinical, hematological, and radiological assessments, were conducted before and after intravenous injection of preconditioned cells in three feline subjects.

Results: 25 μM DFO pretreatment significantly up-regulated immunomodulatory genes (Tgfb, Hgf, and Tsg-6) in fATMSCs. In the mouse ALI model, DFO-pretreated fATMSCs exhibited enhanced anti-inflammatory effects, reducing inflammatory cytokines (Tnfa, Il1b, Il6). Clinical safety assessment in felines showed no immediate adverse effects, structural alterations, or tumorigenesis.

Conclusion: Utilizing a mouse model of acute lung injury, we demonstrated the potential of DFO-pretreated fATMSCs as a safe and effective therapeutic approach for inflammatory disorders.

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去铁胺（DFO）预处理猫脂肪间充质干细胞安全性和有效性的临床前评估。

背景/目的：本研究旨在探讨去铁胺（DFO）预处理猫脂肪组织源性间充质干细胞（fATMSCs）治疗炎性疾病的安全性和有效性。材料和方法：从猫脂肪组织中分离出fATMSCs，并使用流式细胞术进行表面标记物表达和脂肪、成骨和软骨谱系分化分析。使用不同浓度的DFO来评估其对fATMSC活性的影响。通过LPS注射急性肺损伤（ALI）小鼠模型验证了这些预处理细胞的治疗潜力。综合评估，包括临床、血液学和放射学评估，在静脉注射预处理细胞之前和之后对三只猫进行了评估。结果：25 μM DFO预处理显著上调fATMSCs的免疫调节基因（Tgfb、Hgf、Tsg-6）。在小鼠ALI模型中，dfo预处理的fATMSCs表现出增强的抗炎作用，降低炎症因子（Tnfa, Il1b, Il6）。在猫身上的临床安全性评估显示没有立即的不良反应、结构改变或肿瘤发生。结论：利用小鼠急性肺损伤模型，我们证明了dfo预处理的fATMSCs作为一种安全有效的炎症性疾病治疗方法的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

In vivo 医学-医学：研究与实验

CiteScore

4.20

自引率

4.30%

发文量

330

审稿时长

3-8 weeks

期刊介绍： IN VIVO is an international peer-reviewed journal designed to bring together original high quality works and reviews on experimental and clinical biomedical research within the frames of physiology, pathology and disease management. The topics of IN VIVO include: 1. Experimental development and application of new diagnostic and therapeutic procedures; 2. Pharmacological and toxicological evaluation of new drugs, drug combinations and drug delivery systems; 3. Clinical trials; 4. Development and characterization of models of biomedical research; 5. Cancer diagnosis and treatment; 6. Immunotherapy and vaccines; 7. Radiotherapy, Imaging; 8. Tissue engineering, Regenerative medicine; 9. Carcinogenesis.