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高危神经母细胞瘤中胎盘来源与骨髓来源间充质基质细胞的体内肿瘤归巢能力比较

A Comparison of in vivo Tumor-Homing Abilities of Placental-Derived and Bone Marrow-Derived Mesenchymal Stromal Cells in High-Risk Neuroblastoma.

作者信息

Doyle Kathleen, Hassan Abd-Elrahman, Sutter Maria, Rodriguez Monica, Kumar Priyadarsini, Brown Erin

机构信息

Department of Surgery, University of California-Davis, Sacramento, CA, USA.

Department of Surgery, University of California-Davis, Sacramento, CA, USA.

出版信息

J Pediatr Surg. 2025 Jan;60(1):161954. doi: 10.1016/j.jpedsurg.2024.161954. Epub 2024 Sep 21.

DOI:10.1016/j.jpedsurg.2024.161954
PMID:39379183
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12068278/
Abstract

BACKGROUND

Neuroblastoma is a highly lethal malignancy of young children. Mesenchymal stromal cells (MSCs) may represent a novel cellular delivery vehicle due to their innate tumor-homing properties. We compared in vivo homing abilities of placental-derived MSCs (PMSCs) and bone marrow-derived MSCs (BM-MSCs) in an orthotopic neuroblastoma xenograft.

METHODS

28 mice underwent direct implantation of neuroblastoma cells (cell line NB1643) into the adrenal gland followed by intraperitoneal injection of 5 × 10 MSCs (PMSC n = 13, BM-MSC n = 13, PBS controls n = 2). MSC migration was monitored with in vivo imaging system (IVIS) radiance measurements at multiple timepoints post-MSC injection. Necropsy timepoints were 72 h (n = 10) and 7 days (n = 16). Ex vivo imaging was performed on all adrenal masses and select organ tissues. Immunohistochemistry (IHC) assessed the presence of MSCs in tumors.

RESULTS

IVIS demonstrated initial diffuse signal that migrated to the left abdomen. Radiance decreased over time, but MSC signal persisted at day 7 in all animals. Ex vivo IVIS demonstrated signal in the adrenal tumor but not other organs. There was no significant difference in average ex vivo adrenal mass radiance between MSC groups (p = 0.74). IHC confirmed presence of both MSC types within the tumor.

CONCLUSION

PMSCs and BM-MSCs successfully migrated to neuroblastoma tumor tissues in vivo without evidence of migration to other organs. MSCs migrate within 72 h and persisted within the tumor up to 7 days. There was no significant difference in homing capabilities of PMSCs compared to BM-MSCs, indicating that either cell type has potential as a drug delivery vehicle.

TYPE OF STUDY

Original Research.

LEVEL OF EVIDENCE

n/a.

摘要

背景

神经母细胞瘤是一种对幼儿具有高度致死性的恶性肿瘤。间充质基质细胞(MSC)因其固有的肿瘤归巢特性,可能代表一种新型的细胞递送载体。我们在原位神经母细胞瘤异种移植模型中比较了胎盘来源的MSC(PMSC)和骨髓来源的MSC(BM-MSC)的体内归巢能力。

方法

28只小鼠接受将神经母细胞瘤细胞(细胞系NB1643)直接植入肾上腺,随后腹腔注射5×10的MSC(PMSC组n = 13,BM-MSC组n = 13,PBS对照组n = 2)。在注射MSC后的多个时间点,用体内成像系统(IVIS)的辐射度测量来监测MSC的迁移。尸检时间点为72小时(n = 10)和7天(n = 16)。对所有肾上腺肿块和选定的器官组织进行离体成像。免疫组织化学(IHC)评估肿瘤中MSC的存在情况。

结果

IVIS显示最初的弥漫性信号迁移到左腹部。辐射度随时间下降,但在第7天所有动物体内的MSC信号仍然存在。离体IVIS显示肾上腺肿瘤中有信号,但其他器官中没有。MSC组之间的离体肾上腺肿块平均辐射度没有显著差异(p = 0.74)。IHC证实肿瘤内两种类型的MSC均存在。

结论

PMSC和BM-MSC在体内成功迁移到神经母细胞瘤肿瘤组织,没有迁移到其他器官的证据。MSC在72小时内迁移,并在肿瘤内持续存在长达7天。与BM-MSC相比,PMSC的归巢能力没有显著差异,表明这两种细胞类型都有作为药物递送载体的潜力。

研究类型

原创研究。

证据水平

无。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330e/12068278/cd490fc687c5/nihms-2071604-f0009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330e/12068278/d512c365a97a/nihms-2071604-f0006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330e/12068278/cd490fc687c5/nihms-2071604-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330e/12068278/ca337f006a37/nihms-2071604-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330e/12068278/483d27b6ad96/nihms-2071604-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330e/12068278/0c559650b4a6/nihms-2071604-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330e/12068278/714139e8521e/nihms-2071604-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330e/12068278/d512c365a97a/nihms-2071604-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330e/12068278/8f62080f5529/nihms-2071604-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330e/12068278/cd490fc687c5/nihms-2071604-f0009.jpg

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本文引用的文献

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J Pediatr Surg. 2024 Aug;59(8):1582-1590. doi: 10.1016/j.jpedsurg.2024.02.014. Epub 2024 Feb 26.
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Development of a Simple and Reproducible Cell-derived Orthotopic Xenograft Murine Model for Neuroblastoma.建立一种简单且可重现的源于神经母细胞瘤的细胞原位异种移植小鼠模型。
In Vivo. 2024 Mar-Apr;38(2):531-538. doi: 10.21873/invivo.13471.
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The potential use of mesenchymal stem cells-derived exosomes as microRNAs delivery systems in different diseases.
间充质干细胞衍生的外泌体作为微 RNA 递药系统在不同疾病中的潜在应用。
Cell Commun Signal. 2023 Jan 23;21(1):20. doi: 10.1186/s12964-022-01017-9.
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Persistency of Mesenchymal Stromal/Stem Cells in Lungs.间充质基质/干细胞在肺部的持久性。
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The quest to develop an effective therapy for neuroblastoma.寻找治疗神经母细胞瘤的有效疗法。
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