Genomic and transcriptomic quality control for an autologous iPSC-derived cell therapy for Parkinson’s disease

IF 23.3 1区医学 Q1 CELL & TISSUE ENGINEERING

Cell stem cell Pub Date : 2026-09-17 DOI:10.1016/j.stem.2026.08.014

Andres M. Bratt-Leal,Thorsten Gorba,Roy M. Williams,Jim A. Mossman,Rachel Hills,Ha Tran,Derren Barken,Genevieve Beauvais,Daniel Fremgen,Ai Zhang,Cullen Pivaroff,Candace Lynch,Yanzheng Liu,Chandnee Chandrasekaran,David Tastad,Charlotte Bridge,Dustin R. Wakeman,Uyen Nguyen,Brent Chamberlain,Emma L. Lane,Mariah J. Lelos,Jeanne F. Loring,Edward D. Wirth III,Xiaokui Zhang

{"title":"Genomic and transcriptomic quality control for an autologous iPSC-derived cell therapy for Parkinson’s disease","authors":"Andres M. Bratt-Leal,Thorsten Gorba,Roy M. Williams,Jim A. Mossman,Rachel Hills,Ha Tran,Derren Barken,Genevieve Beauvais,Daniel Fremgen,Ai Zhang,Cullen Pivaroff,Candace Lynch,Yanzheng Liu,Chandnee Chandrasekaran,David Tastad,Charlotte Bridge,Dustin R. Wakeman,Uyen Nguyen,Brent Chamberlain,Emma L. Lane,Mariah J. Lelos,Jeanne F. Loring,Edward D. Wirth III,Xiaokui Zhang","doi":"10.1016/j.stem.2026.08.014","DOIUrl":null,"url":null,"abstract":"Toward development of an autologous, induced pluripotent stem cell (iPSC)-based cell therapy for Parkinson’s disease (PD), we demonstrate successful, reproducible genomic and transcriptomic qualification of patient-derived dopaminergic neuron precursor cells (DANPCs) across multiple donors. Our analysis includes whole-genome sequencing data from fibroblasts, iPSCs, and DANPCs and the development of NeuriTest, an RNAseq-based bioinformatic analysis of DANPCs designed to predict cell quality based on empirical animal data. Autologous cell therapies are immune matched to the patient, potentially augmenting durability of benefit compared to allogeneic cells while negating the need for immunosuppression and accompanying side effects. Patient-specific iPSCs are an autologous cell source that can be differentiated to dopaminergic neurons, the cell type lost in PD. We report here our preclinical manufacturing strategy and results demonstrating efficacy in a PD rodent model and safety in a 9-month GLP toxicology study.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"20 1","pages":""},"PeriodicalIF":23.3000,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell stem cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.stem.2026.08.014","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}

引用次数: 0

Abstract

Toward development of an autologous, induced pluripotent stem cell (iPSC)-based cell therapy for Parkinson’s disease (PD), we demonstrate successful, reproducible genomic and transcriptomic qualification of patient-derived dopaminergic neuron precursor cells (DANPCs) across multiple donors. Our analysis includes whole-genome sequencing data from fibroblasts, iPSCs, and DANPCs and the development of NeuriTest, an RNAseq-based bioinformatic analysis of DANPCs designed to predict cell quality based on empirical animal data. Autologous cell therapies are immune matched to the patient, potentially augmenting durability of benefit compared to allogeneic cells while negating the need for immunosuppression and accompanying side effects. Patient-specific iPSCs are an autologous cell source that can be differentiated to dopaminergic neurons, the cell type lost in PD. We report here our preclinical manufacturing strategy and results demonstrating efficacy in a PD rodent model and safety in a 9-month GLP toxicology study.

Abstract Image

查看原文本刊更多论文

自体ipsc衍生细胞治疗帕金森病的基因组和转录组质量控制

为了开发一种基于自体诱导多能干细胞（iPSC）的帕金森氏病（PD）细胞疗法，我们在多个供体中成功地验证了患者来源的多巴胺能神经元前体细胞（DANPCs）的基因组和转录组学鉴定。我们的分析包括来自成纤维细胞、iPSCs和DANPCs的全基因组测序数据，以及基于rnaseq的DANPCs生物信息学分析NeuriTest的开发，该分析旨在根据经验动物数据预测细胞质量。自体细胞疗法与患者免疫匹配，与异体细胞相比，潜在地增加了获益的持久性，同时消除了免疫抑制和伴随的副作用。患者特异性iPSCs是一种自体细胞来源，可以分化为多巴胺能神经元，这是PD中缺失的细胞类型。我们在此报告我们的临床前生产策略和结果，证明了PD啮齿动物模型的有效性和9个月GLP毒理学研究的安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell stem cell 生物-细胞生物学

CiteScore

37.10

自引率

2.50%

发文量

151

审稿时长

42 days

期刊介绍： Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.