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人未成熟牙髓干细胞未植入预先存在的人肺腺癌

英文原题:Human Immature Dental Pulp Stem Cells Did Not Graft into a Preexisting Human Lung Adenocarcinoma.

查看英文原题

Human Immature Dental Pulp Stem Cells Did Not Graft into a Preexisting Human Lung Adenocarcinoma.

PubMed 2022/04/21(内容时间) Case Rep Oncol Q4 · IF 0.7(JCR 2025)

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中文摘要

间充质干细胞(MSC)疗法被认为是治疗亨廷顿病(HD)的有吸引力方案。然而,由于静脉输注(最常用MSC给药途径)存在肺部首过效应,人们日益担忧细胞可能滞留于肺并植入(归巢至)既存肺癌。本报告介绍一例参加HD细胞治疗I期临床试验的患者,该患者原有肺结节。筛查时发现该结节。患者转诊至肺科医生,经评估认为结节并非癌症并同意患者入组。患者在2年内接受4次人未成熟牙髓干细胞(hIDPSC)静脉输注,剂量为每千克体重1×10^6个细胞。末次给药后1个月,计算机断层扫描显示结节增大。支气管镜活检证实为原发性肺腺癌。患者接受手术切除(右肺上叶切除术)后治愈。将肿瘤切成6块并进行RNA测序。采用主成分分析和NOIseq两种统计方法,将每块肿瘤的转录组与输注的hIDPSC转录组比较。两种分析均显示hIDPSC与肺腺癌之间存在明显线性距离。结果提示,输注的hIDPSC既未归巢到肺结节,也未植入其中。

展开英文摘要原文

Mesenchymal stem cell (MSC)-based therapies have been considered an attractive approach for treating Huntington's disease (HD).

However, due to the pulmonary first-passage effect associated with intravenous infusion (the most commonly used route of MSC administration), there is a rising concern that the cells could be entrapped in the lungs and grafted (homing) into preexisting lung cancer.

Herein, we report the case of a patient with HD enrolled in a cell therapy phase I clinical trial for HD treatment having a preexisting pulmonary nodule. The nodule was found at the trial screening. The patient was referred to a pulmonologist who considered the nodule non-cancer and authorized enrollment. The patient received four intravenous administrations of human immature dental pulp stem cells (hIDPSCs) at the dose of 1 10 6 cells/kg of body weight within 2 years. One month after the last dose, a computerized tomography scan showed nodule growth.

A bronchoscopy biopsy showed primary lung adenocarcinoma. The neoplasm was surgically excised (lung superior right lobectomy). The patient is cured of the neoplasm. The tumor was sectioned into six fragments, which were subjected to RNA-seq.

The transcriptome of each tumor section was compared with the transcriptome of infused hIDPSCs using two statistical approaches: principal component analysis and NOIseq. Both results demonstrated a linear distance between the hIDPSCs and the lung adenocarcinoma. These results suggest that the infused hIDPSCs neither home nor graft within the pulmonary nodule.

论文信息

作者
da Silva JM、Araldi RP、Colozza-Gama GA、Pagani E、Sid A、Valverde CW、Kerkis I
第一作者单位
Azidus Brazil, São Paulo, Brazil.Brazil
通讯作者单位
Genetics Laboratory, Butantan Institute, São Paulo, Brazil.Brazil
文献类型
病例报告
期刊
Case reports in oncology2022 Jan-Apr
原文标识
PubMed 35702561 · DOI 10.1159/000523896