22(R)-hydroxycholesterol for dopaminergic neuronal specification of MSCs and amelioration of Parkinsonian symptoms in rats
Abstract Oxysterols play vital roles in the human body, ranging from cell cycle regulation and progression to dopaminergic neurogenesis. While naïve human mesenchymal stem cells (hMSCs) have been explored to have neurogenic effect, there is still a grey area to explore their regenerative potential a...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-01-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-020-00351-6 |
| _version_ | 1828242205550051328 |
|---|---|
| author | Manisha Singh Manish Jain Samrat Bose Ashutosh Halder Tapas Chandra Nag Amit Kumar Dinda Sujata Mohanty |
| author_facet | Manisha Singh Manish Jain Samrat Bose Ashutosh Halder Tapas Chandra Nag Amit Kumar Dinda Sujata Mohanty |
| author_sort | Manisha Singh |
| collection | DOAJ |
| description | Abstract Oxysterols play vital roles in the human body, ranging from cell cycle regulation and progression to dopaminergic neurogenesis. While naïve human mesenchymal stem cells (hMSCs) have been explored to have neurogenic effect, there is still a grey area to explore their regenerative potential after in vitro differentiation. Hence, in the current study, we have investigated the neurogenic effect of 22(R)-hydroxycholesterol (22-HC) on hMSCs obtained from bone marrow, adipose tissue and dental pulp. Morphological and morphometric analysis revealed physical differentiation of stem cells into neuronal cells. Detailed characterization of differentiated cells affirmed generation of neuronal cells in culture. The percentage of generation of non-DA cells in the culture confirmed selective neurogenic potential of 22-HC. We substantiated the efficacy of these cells in neuro-regeneration by transplanting them into Parkinson’s disease Wistar rat model. MSCs from dental pulp had maximal regenerative effect (with 80.20 ± 1.5% in vitro differentiation efficiency) upon transplantation, as shown by various behavioural examinations and immunohistochemical tests. Subsequential analysis revealed that 22-HC yields a higher percentage of functional DA neurons and has differential effect on various tissue-specific primary human MSCs. 22-HC may be used for treating Parkinson’s disease in future with stem cells. |
| first_indexed | 2024-04-12T22:12:23Z |
| format | Article |
| id | doaj.art-cd287bfa6ff24d2f8d50a48de10c80ed |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-12T22:12:23Z |
| publishDate | 2021-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-cd287bfa6ff24d2f8d50a48de10c80ed2022-12-22T03:14:43ZengNature Publishing GroupCell Death Discovery2058-77162021-01-017111710.1038/s41420-020-00351-622(R)-hydroxycholesterol for dopaminergic neuronal specification of MSCs and amelioration of Parkinsonian symptoms in ratsManisha Singh0Manish Jain1Samrat Bose2Ashutosh Halder3Tapas Chandra Nag4Amit Kumar Dinda5Sujata Mohanty6Stem Cell Facility (DBT-Centre of Excellence for Stem Cell Research), All India Institute of Medical SciencesDepartment of Reproductive Biology, All India Institute of Medical SciencesDepartment of Physiology, All India Institute of Medical SciencesDepartment of Reproductive Biology, All India Institute of Medical SciencesSophisticated Analytical Instrumentation Facility, All India Institute of Medical SciencesDepartment of Pathology, All India Institute of Medical SciencesStem Cell Facility (DBT-Centre of Excellence for Stem Cell Research), All India Institute of Medical SciencesAbstract Oxysterols play vital roles in the human body, ranging from cell cycle regulation and progression to dopaminergic neurogenesis. While naïve human mesenchymal stem cells (hMSCs) have been explored to have neurogenic effect, there is still a grey area to explore their regenerative potential after in vitro differentiation. Hence, in the current study, we have investigated the neurogenic effect of 22(R)-hydroxycholesterol (22-HC) on hMSCs obtained from bone marrow, adipose tissue and dental pulp. Morphological and morphometric analysis revealed physical differentiation of stem cells into neuronal cells. Detailed characterization of differentiated cells affirmed generation of neuronal cells in culture. The percentage of generation of non-DA cells in the culture confirmed selective neurogenic potential of 22-HC. We substantiated the efficacy of these cells in neuro-regeneration by transplanting them into Parkinson’s disease Wistar rat model. MSCs from dental pulp had maximal regenerative effect (with 80.20 ± 1.5% in vitro differentiation efficiency) upon transplantation, as shown by various behavioural examinations and immunohistochemical tests. Subsequential analysis revealed that 22-HC yields a higher percentage of functional DA neurons and has differential effect on various tissue-specific primary human MSCs. 22-HC may be used for treating Parkinson’s disease in future with stem cells.https://doi.org/10.1038/s41420-020-00351-6 |
| spellingShingle | Manisha Singh Manish Jain Samrat Bose Ashutosh Halder Tapas Chandra Nag Amit Kumar Dinda Sujata Mohanty 22(R)-hydroxycholesterol for dopaminergic neuronal specification of MSCs and amelioration of Parkinsonian symptoms in rats Cell Death Discovery |
| title | 22(R)-hydroxycholesterol for dopaminergic neuronal specification of MSCs and amelioration of Parkinsonian symptoms in rats |
| title_full | 22(R)-hydroxycholesterol for dopaminergic neuronal specification of MSCs and amelioration of Parkinsonian symptoms in rats |
| title_fullStr | 22(R)-hydroxycholesterol for dopaminergic neuronal specification of MSCs and amelioration of Parkinsonian symptoms in rats |
| title_full_unstemmed | 22(R)-hydroxycholesterol for dopaminergic neuronal specification of MSCs and amelioration of Parkinsonian symptoms in rats |
| title_short | 22(R)-hydroxycholesterol for dopaminergic neuronal specification of MSCs and amelioration of Parkinsonian symptoms in rats |
| title_sort | 22 r hydroxycholesterol for dopaminergic neuronal specification of mscs and amelioration of parkinsonian symptoms in rats |
| url | https://doi.org/10.1038/s41420-020-00351-6 |
| work_keys_str_mv | AT manishasingh 22rhydroxycholesterolfordopaminergicneuronalspecificationofmscsandameliorationofparkinsoniansymptomsinrats AT manishjain 22rhydroxycholesterolfordopaminergicneuronalspecificationofmscsandameliorationofparkinsoniansymptomsinrats AT samratbose 22rhydroxycholesterolfordopaminergicneuronalspecificationofmscsandameliorationofparkinsoniansymptomsinrats AT ashutoshhalder 22rhydroxycholesterolfordopaminergicneuronalspecificationofmscsandameliorationofparkinsoniansymptomsinrats AT tapaschandranag 22rhydroxycholesterolfordopaminergicneuronalspecificationofmscsandameliorationofparkinsoniansymptomsinrats AT amitkumardinda 22rhydroxycholesterolfordopaminergicneuronalspecificationofmscsandameliorationofparkinsoniansymptomsinrats AT sujatamohanty 22rhydroxycholesterolfordopaminergicneuronalspecificationofmscsandameliorationofparkinsoniansymptomsinrats |