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基于悬浮基质的弥漫性中线胶质瘤患者来源异种移植小鼠模型标准化用于临床前研究

Towards Standardisation of a Diffuse Midline Glioma Patient-Derived Xenograft Mouse Model Based on Suspension Matrices for Preclinical Research.

作者信息

't Hart Elvin, Bianco John, Besse Helena C, Chin Joe Kie Lois A, Cornet Lesley, Eikelenboom Kimberly L, van den Broek Thijs J M, Derieppe Marc, Su Yan, Hoving Eelco W, Ries Mario G, van Vuurden Dannis G

机构信息

Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.

Center for Imaging Sciences, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.

出版信息

Biomedicines. 2023 Feb 11;11(2):527. doi: 10.3390/biomedicines11020527.

DOI:10.3390/biomedicines11020527
PMID:36831063
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9952880/
Abstract

Diffuse midline glioma (DMG) is an aggressive brain tumour with high mortality and limited clinical therapeutic options. Although in vitro research has shown the effectiveness of medication, successful translation to the clinic remains elusive. A literature search highlighted the high variability and lack of standardisation in protocols applied for establishing the commonly used HSJD-DIPG-007 patient-derived xenograft (PDX) model, based on animal host, injection location, number of cells inoculated, volume, and suspension matrices. This study evaluated the HSJD-DIPG-007 PDX model with respect to its ability to mimic human disease progression for therapeutic testing in vivo. The mice received intracranial injections of HSJD-DIPG-007 cells suspended in either PBS or Matrigel. Survival, tumour growth, and metastases were assessed to evaluate differences in the suspension matrix used. After cell implantation, no severe side effects were observed. Additionally, no differences were detected in terms of survival or tumour growth between the two suspension groups. We observed delayed metastases in the Matrigel group, with a significant difference compared to mice with PBS-suspended cells. In conclusion, using Matrigel as a suspension matrix is a reliable method for establishing a DMG PDX mouse model, with delayed metastases formation and is a step forward to obtaining a standardised in vivo PDX model.

摘要

弥漫性中线胶质瘤(DMG)是一种侵袭性脑肿瘤,死亡率高,临床治疗选择有限。尽管体外研究已显示药物的有效性,但成功转化至临床仍难以实现。文献检索突出表明,在用于建立常用的HSJD-DIPG-007患者来源异种移植(PDX)模型的方案中,存在高度变异性且缺乏标准化,这些方案涉及动物宿主、注射部位、接种细胞数量、体积和悬浮基质。本研究评估了HSJD-DIPG-007 PDX模型在体内模拟人类疾病进展以进行治疗测试的能力。小鼠接受了颅内注射悬浮于PBS或基质胶中的HSJD-DIPG-007细胞。评估了生存率、肿瘤生长和转移情况,以评估所用悬浮基质的差异。细胞植入后,未观察到严重副作用。此外,两个悬浮组在生存率或肿瘤生长方面未检测到差异。我们观察到基质胶组出现转移延迟,与悬浮于PBS中的细胞的小鼠相比有显著差异。总之,使用基质胶作为悬浮基质是建立DMG PDX小鼠模型的可靠方法,可延迟转移形成,是朝着获得标准化体内PDX模型迈出的一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/e5814e10bc49/biomedicines-11-00527-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/b08e8eca7b86/biomedicines-11-00527-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/39deb34760c5/biomedicines-11-00527-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/40c6cc3f496b/biomedicines-11-00527-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/a50238bc9b08/biomedicines-11-00527-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/324b09e824e0/biomedicines-11-00527-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/e5814e10bc49/biomedicines-11-00527-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/b08e8eca7b86/biomedicines-11-00527-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/39deb34760c5/biomedicines-11-00527-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/40c6cc3f496b/biomedicines-11-00527-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/a50238bc9b08/biomedicines-11-00527-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/324b09e824e0/biomedicines-11-00527-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce8/9952880/e5814e10bc49/biomedicines-11-00527-g006.jpg

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