CD200-based cell sorting results in homogeneous transplantable striatal neuroblasts for human cell therapy for Huntington's disease

IF 5.1 2区医学 Q1 NEUROSCIENCES

Neurobiology of Disease Pub Date : 2025-04-10 DOI:10.1016/j.nbd.2025.106905

Francisco J. Molina-Ruiz , Phil Sanders , Cinta Gomis , Jordi Abante , Francisco Londoño , Georgina Bombau , Mireia Galofré , Gal la Vinyes-Bassols , Veronica Monforte , Josep M. Canals

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引用次数: 0

Abstract

Neurodegenerative diseases are characterized by selective loss of neurons. Cell replacement therapies are the most promising therapeutic strategies to restore the neuronal functions lost during these neurodegenerative processes. However, cell replacement-based clinical trials for Huntington's (HD) and Parkinson's diseases (PD) failed due to the large heterogeneity of the samples.

Here, we identify CD200 as a cell surface marker for human striatal neuroblasts (NBs) using massively parallel single-cell RNA sequencing. Next, we set up a CD200-based immunomagnetic sorting pipeline that allows high-yield enrichment of human striatal NBs from in vitro differentiation of human pluripotent stem cells (hPSCs). We also show that sorted CD200-positive cells are striatal projection neuron (SPN)-committed NBs which survive upon intra-striatal transplantation in adult mice with no evidence of graft overgrowth in vivo.

In conclusion, we implemented a new CD200 cell selection strategy that reduces the heterogeneity and batch-to-batch variation and potentially decreases the teratogenic risk of hPSC-based cell therapy for neurodegenerative diseases.

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基于cd200的细胞分选结果可用于亨廷顿氏病的人类细胞治疗的均匀可移植纹状体神经母细胞

神经退行性疾病的特点是神经元的选择性丧失。细胞替代疗法是最有希望的治疗策略，以恢复在这些神经退行性过程中失去的神经元功能。然而，基于细胞替代的亨廷顿舞蹈症（HD）和帕金森病（PD）的临床试验由于样本的巨大异质性而失败。在这里，我们使用大规模平行单细胞RNA测序鉴定了CD200作为人类纹状体神经母细胞（NBs）的细胞表面标记物。接下来，我们建立了一个基于cd200的免疫磁分选管道，该管道允许从人多能干细胞（hPSCs）的体外分化中高产富集人纹状体NBs。我们还发现，分选的cd200阳性细胞是纹状体投射神经元（SPN）承诺的NBs，它们在成年小鼠纹状体内移植后存活，在体内没有移植物过度生长的证据。总之，我们实施了一种新的CD200细胞选择策略，减少了异质性和批间变异，并潜在地降低了基于hpsc的细胞治疗神经退行性疾病的致畸风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.