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基于生物分布的 cGMP 合规人脐带间充质干细胞给药方式影响创伤愈合的治疗效果。

Biodistribution-based Administration of cGMP-compliant Human Umbilical Cord Mesenchymal Stem Cells Affects the Therapeutic Effect of Wound Healing.

机构信息

Qilu Cell Therapy Technology Co., Ltd, Gangyuan 6th Road, Licheng District, Ji'nan, Shandong, 250000, People's Republic of China.

School of Medicine, Northwest University, Xi'an, China.

出版信息

Stem Cell Rev Rep. 2024 Jan;20(1):329-346. doi: 10.1007/s12015-023-10644-9. Epub 2023 Oct 27.

Abstract

BACKGROUND

Although mesenchymal stem cells (MSCs) are used as therapeutic agents for skin injury therapy, few studies have reported the effects of dosing duration and delivery frequency on wound healing. In addition, before the clinical application of MSCs, it is important to assess whether their usage might influence tumor occurrence.

METHODS

We described the metabolic patterns of subcutaneous injection of hUC-MSCs using fluorescence tracing and qPCR methods and applied them to the development of drug delivery strategies for promoting wound healing.

RESULTS

(i) We developed cGMP-compliant hUC-MSC products with critical quality control points for wound healing; (ii) The products did not possess any tumorigenic or tumor-promoting/inhibiting ability in vivo; (iii) Fluorescence tracing and qPCR analyses showed that the subcutaneous application of hUC-MSCs did not result in safety-relevant biodistribution or ectopic migration; (iv) Reinjecting hUC-MSCs after significant consumption significantly improved reepithelialization and dermal regeneration.

CONCLUSIONS

Our findings provided a reference for controlling the quality of MSC products used for wound healing and highlighted the importance of delivery time and frequency for designing in vivo therapeutic studies.

摘要

背景

间充质干细胞(MSCs)被用作皮肤损伤治疗的治疗剂,但很少有研究报道剂量持续时间和给药频率对伤口愈合的影响。此外,在 MSC 的临床应用之前,评估其使用是否可能影响肿瘤发生非常重要。

方法

我们使用荧光示踪和 qPCR 方法描述了皮下注射 hUC-MSCs 的代谢模式,并将其应用于促进伤口愈合的药物输送策略的开发。

结果

(i)我们开发了符合 cGMP 标准的 hUC-MSC 产品,具有伤口愈合的关键质量控制点;(ii)这些产品在体内没有任何致瘤性或促进/抑制肿瘤的能力;(iii)荧光示踪和 qPCR 分析表明,hUC-MSCs 的皮下应用不会导致与安全性相关的生物分布或异位迁移;(iv)在大量消耗后重新注射 hUC-MSCs 可显著改善再上皮化和真皮再生。

结论

我们的研究结果为控制用于伤口愈合的 MSC 产品的质量提供了参考,并强调了设计体内治疗研究时给药时间和频率的重要性。

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