Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down Syndrome
Down syndrome (DS), or trisomy 21, is manifested in a variety of anatomical and cellular abnormalities resulting in intellectual deficits and early onset of Alzheimer’s disease (AD) with no effective treatments available to alleviate the pathologies associated with the disorder. The therapeutic pote...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3477 |
| _version_ | 1797620538047201280 |
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| author | Natalie Baker Campbell Yesha Patel Tara L. Moore Maria Medalla Ella Zeldich |
| author_facet | Natalie Baker Campbell Yesha Patel Tara L. Moore Maria Medalla Ella Zeldich |
| author_sort | Natalie Baker Campbell |
| collection | DOAJ |
| description | Down syndrome (DS), or trisomy 21, is manifested in a variety of anatomical and cellular abnormalities resulting in intellectual deficits and early onset of Alzheimer’s disease (AD) with no effective treatments available to alleviate the pathologies associated with the disorder. The therapeutic potential of extracellular vesicles (EVs) has emerged recently in relation to various neurological conditions. We have previously demonstrated the therapeutic efficacy of mesenchymal stromal cell-derived EVs (MSC-EVs) in cellular and functional recovery in a rhesus monkey model of cortical injury. In the current study, we evaluated the therapeutic effect of MSC-EVs in a cortical spheroid (CS) model of DS generated from patient-derived induced pluripotent stem cells (iPSCs). Compared to euploid controls, trisomic CS display smaller size, deficient neurogenesis, and AD-related pathological features, such as enhanced cell death and depositions of amyloid beta (Aβ) and hyperphosphorylated tau (p-tau). EV-treated trisomic CS demonstrated preserved size, partial rescue in the production of neurons, significantly decreased levels of Aβ and p-tau, and a reduction in the extent of cell death as compared to the untreated trisomic CS. Together, these results show the efficacy of EVs in mitigating DS and AD-related cellular phenotypes and pathological depositions in human CS. |
| first_indexed | 2024-03-11T08:42:58Z |
| format | Article |
| id | doaj.art-6b6853d05b9745d4ba8ad642f9901b7a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:42:58Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6b6853d05b9745d4ba8ad642f9901b7a2023-11-16T21:00:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244347710.3390/ijms24043477Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down SyndromeNatalie Baker Campbell0Yesha Patel1Tara L. Moore2Maria Medalla3Ella Zeldich4Department of Anatomy & Neurobiology, Boston University Chobanian & Avedesian School of Medicine, Boston University, Boston, MA 02118, USACommonwealth Honors College, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Anatomy & Neurobiology, Boston University Chobanian & Avedesian School of Medicine, Boston University, Boston, MA 02118, USADepartment of Anatomy & Neurobiology, Boston University Chobanian & Avedesian School of Medicine, Boston University, Boston, MA 02118, USADepartment of Anatomy & Neurobiology, Boston University Chobanian & Avedesian School of Medicine, Boston University, Boston, MA 02118, USADown syndrome (DS), or trisomy 21, is manifested in a variety of anatomical and cellular abnormalities resulting in intellectual deficits and early onset of Alzheimer’s disease (AD) with no effective treatments available to alleviate the pathologies associated with the disorder. The therapeutic potential of extracellular vesicles (EVs) has emerged recently in relation to various neurological conditions. We have previously demonstrated the therapeutic efficacy of mesenchymal stromal cell-derived EVs (MSC-EVs) in cellular and functional recovery in a rhesus monkey model of cortical injury. In the current study, we evaluated the therapeutic effect of MSC-EVs in a cortical spheroid (CS) model of DS generated from patient-derived induced pluripotent stem cells (iPSCs). Compared to euploid controls, trisomic CS display smaller size, deficient neurogenesis, and AD-related pathological features, such as enhanced cell death and depositions of amyloid beta (Aβ) and hyperphosphorylated tau (p-tau). EV-treated trisomic CS demonstrated preserved size, partial rescue in the production of neurons, significantly decreased levels of Aβ and p-tau, and a reduction in the extent of cell death as compared to the untreated trisomic CS. Together, these results show the efficacy of EVs in mitigating DS and AD-related cellular phenotypes and pathological depositions in human CS.https://www.mdpi.com/1422-0067/24/4/3477Down syndromeAlzheimer’s diseasebrain organoidsextracellular vesiclesmesenchymal stem cellstrisomy |
| spellingShingle | Natalie Baker Campbell Yesha Patel Tara L. Moore Maria Medalla Ella Zeldich Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down Syndrome International Journal of Molecular Sciences Down syndrome Alzheimer’s disease brain organoids extracellular vesicles mesenchymal stem cells trisomy |
| title | Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down Syndrome |
| title_full | Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down Syndrome |
| title_fullStr | Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down Syndrome |
| title_full_unstemmed | Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down Syndrome |
| title_short | Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down Syndrome |
| title_sort | extracellular vesicle treatment alleviates neurodevelopmental and neurodegenerative pathology in cortical spheroid model of down syndrome |
| topic | Down syndrome Alzheimer’s disease brain organoids extracellular vesicles mesenchymal stem cells trisomy |
| url | https://www.mdpi.com/1422-0067/24/4/3477 |
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