期刊论文详细信息
Stem Cell Research & Therapy
Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial
Allan B. Dietz1  Joseph Hart2  Nathan P. Staff2  Sybil C. L. Hrstka2  Anthony J. Windebank2  Ashley A. Krull2  Michael J. Polzin2  Nicolas N. Madigan2  Deborah O. Setter2  Tania F. Gendron3  Amel Dudakovic4  Andre J. van Wijnen4 
[1] Department of Laboratory Medicine and Pathology, Mayo Clinic, 55905, Rochester, MN, USA;Department of Neurology, Mayo Clinic, 200 First St. SW, 55905, Rochester, MN, USA;Department of Neuroscience, Mayo Clinic, 32224, Jacksonville, FL, USA;Department of Orthopedic Surgery, Mayo Clinic, 55905, Rochester, MN, USA;
关键词: Mesenchymal stromal cell;    Gene expression;    Neuroinflammation;    Growth factors;    Cerebrospinal fluid;    Amyotrophic lateral sclerosis;    Human studies;   
DOI  :  10.1186/s13287-021-02241-9
来源: Springer
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【 摘 要 】

BackgroundMesenchymal stromal cells (MSCs) have been studied with increasing intensity as clinicians and researchers strive to understand the ability of MSCs to modulate disease progression and promote tissue regeneration. As MSCs are used for diverse applications, it is important to appreciate how specific physiological environments may stimulate changes that alter the phenotype of the cells. One need for neuroregenerative applications is to characterize the spectrum of MSC responses to the cerebrospinal fluid (CSF) environment after their injection into the intrathecal space. Mechanistic understanding of cellular biology in response to the CSF environment may predict the ability of MSCs to promote injury repair or provide neuroprotection in neurodegenerative diseases.MethodsIn this study, we characterized changes in morphology, metabolism, and gene expression occurring in human adipose-derived MSCs cultured in human (hCSF) or artificial CSF (aCSF) as well as examined relevant protein levels in the CSF of subjects treated with MSCs for amyotrophic lateral sclerosis (ALS).ResultsOur results demonstrated that, under intrathecal-like conditions, MSCs retained their morphology, though they became quiescent. Large-scale transcriptomic analysis of MSCs revealed a distinct gene expression profile for cells cultured in aCSF. The aCSF culture environment induced expression of genes related to angiogenesis and immunomodulation. In addition, MSCs in aCSF expressed genes encoding nutritional growth factors to expression levels at or above those of control cells. Furthermore, we observed a dose-dependent increase in growth factors and immunomodulatory cytokines in CSF from subjects with ALS treated intrathecally with autologous MSCs.ConclusionsOverall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.

【 授权许可】

CC BY   

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