Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial
Abstract Background Mesenchymal 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 appre...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-03-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-021-02241-9 |
| _version_ | 1818673355109171200 |
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| author | Ashley A. Krull Deborah O. Setter Tania F. Gendron Sybil C. L. Hrstka Michael J. Polzin Joseph Hart Amel Dudakovic Nicolas N. Madigan Allan B. Dietz Anthony J. Windebank Andre J. van Wijnen Nathan P. Staff |
| author_facet | Ashley A. Krull Deborah O. Setter Tania F. Gendron Sybil C. L. Hrstka Michael J. Polzin Joseph Hart Amel Dudakovic Nicolas N. Madigan Allan B. Dietz Anthony J. Windebank Andre J. van Wijnen Nathan P. Staff |
| author_sort | Ashley A. Krull |
| collection | DOAJ |
| description | Abstract Background Mesenchymal 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. Methods In 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). Results Our 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. Conclusions Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients. |
| first_indexed | 2024-12-17T07:54:28Z |
| format | Article |
| id | doaj.art-47692b6a9c6541b9a0f6a8f7dadecf99 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-17T07:54:28Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-47692b6a9c6541b9a0f6a8f7dadecf992022-12-21T21:57:45ZengBMCStem Cell Research & Therapy1757-65122021-03-0112111410.1186/s13287-021-02241-9Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trialAshley A. Krull0Deborah O. Setter1Tania F. Gendron2Sybil C. L. Hrstka3Michael J. Polzin4Joseph Hart5Amel Dudakovic6Nicolas N. Madigan7Allan B. Dietz8Anthony J. Windebank9Andre J. van Wijnen10Nathan P. Staff11Department of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Orthopedic Surgery, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Orthopedic Surgery, Mayo ClinicDepartment of Neurology, Mayo ClinicAbstract Background Mesenchymal 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. Methods In 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). Results Our 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. Conclusions Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.https://doi.org/10.1186/s13287-021-02241-9Mesenchymal stromal cellGene expressionNeuroinflammationGrowth factorsCerebrospinal fluidAmyotrophic lateral sclerosis |
| spellingShingle | Ashley A. Krull Deborah O. Setter Tania F. Gendron Sybil C. L. Hrstka Michael J. Polzin Joseph Hart Amel Dudakovic Nicolas N. Madigan Allan B. Dietz Anthony J. Windebank Andre J. van Wijnen Nathan P. Staff Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial Stem Cell Research & Therapy Mesenchymal stromal cell Gene expression Neuroinflammation Growth factors Cerebrospinal fluid Amyotrophic lateral sclerosis |
| title | Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial |
| title_full | Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial |
| title_fullStr | Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial |
| title_full_unstemmed | Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial |
| title_short | Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial |
| title_sort | alterations of mesenchymal stromal cells in cerebrospinal fluid insights from transcriptomics and an als clinical trial |
| topic | Mesenchymal stromal cell Gene expression Neuroinflammation Growth factors Cerebrospinal fluid Amyotrophic lateral sclerosis |
| url | https://doi.org/10.1186/s13287-021-02241-9 |
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