Neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of Parkinson’s disease in rats
Neural progenitor cells (NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previou...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=5;spage=1090;epage=1098;aulast=Guo |
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| author | Yu Guo Yuan-Yuan Wang Ting-Ting Sun Jia-Jia Xu Pan Yang Cai-Yun Ma Wei-Jun Guan Chun-Jing Wang Gao-Feng Liu Chang-Qing Liu |
| author_facet | Yu Guo Yuan-Yuan Wang Ting-Ting Sun Jia-Jia Xu Pan Yang Cai-Yun Ma Wei-Jun Guan Chun-Jing Wang Gao-Feng Liu Chang-Qing Liu |
| author_sort | Yu Guo |
| collection | DOAJ |
| description | Neural progenitor cells (NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previous studies have found that a chemical cocktail of valproic acid, CHIR99021, and Repsox (VCR) promotes mouse fibroblasts to differentiate into NPCs under hypoxic conditions. Therefore, we used VCR (0.5 mM valproic acid, 3 μM CHIR99021, and 1 μM Repsox) to induce the reprogramming of rat embryonic fibroblasts into NPCs under a hypoxic condition (5%). These NPCs exhibited typical neurosphere-like structures that can express NPC markers, such as Nestin, SRY-box transcription factor 2, and paired box 6 (Pax6), and could also differentiate into multiple types of functional neurons and astrocytes in vitro. They had similar gene expression profiles to those of rat brain-derived neural stem cells. Subsequently, the chemically-induced NPCs (ciNPCs) were stereotactically transplanted into the substantia nigra of 6-hydroxydopamine-lesioned parkinsonian rats. We found that the ciNPCs exhibited long-term survival, migrated long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Moreover, the parkinsonian behavioral defects of the parkinsonian model rats grafted with ciNPCs showed remarkable functional recovery. These findings suggest that rat fibroblasts can be directly transformed into NPCs using a chemical cocktail of VCR without introducing exogenous factors, which may be an attractive donor material for transplantation therapy for Parkinson’s disease. |
| first_indexed | 2024-04-11T06:46:45Z |
| format | Article |
| id | doaj.art-3d61b03ab8104731b554addcbee65b52 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-04-11T06:46:45Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-3d61b03ab8104731b554addcbee65b522022-12-22T04:39:20ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742023-01-011851090109810.4103/1673-5374.355820Neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of Parkinson’s disease in ratsYu GuoYuan-Yuan WangTing-Ting SunJia-Jia XuPan YangCai-Yun MaWei-Jun GuanChun-Jing WangGao-Feng LiuChang-Qing LiuNeural progenitor cells (NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previous studies have found that a chemical cocktail of valproic acid, CHIR99021, and Repsox (VCR) promotes mouse fibroblasts to differentiate into NPCs under hypoxic conditions. Therefore, we used VCR (0.5 mM valproic acid, 3 μM CHIR99021, and 1 μM Repsox) to induce the reprogramming of rat embryonic fibroblasts into NPCs under a hypoxic condition (5%). These NPCs exhibited typical neurosphere-like structures that can express NPC markers, such as Nestin, SRY-box transcription factor 2, and paired box 6 (Pax6), and could also differentiate into multiple types of functional neurons and astrocytes in vitro. They had similar gene expression profiles to those of rat brain-derived neural stem cells. Subsequently, the chemically-induced NPCs (ciNPCs) were stereotactically transplanted into the substantia nigra of 6-hydroxydopamine-lesioned parkinsonian rats. We found that the ciNPCs exhibited long-term survival, migrated long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Moreover, the parkinsonian behavioral defects of the parkinsonian model rats grafted with ciNPCs showed remarkable functional recovery. These findings suggest that rat fibroblasts can be directly transformed into NPCs using a chemical cocktail of VCR without introducing exogenous factors, which may be an attractive donor material for transplantation therapy for Parkinson’s disease.http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=5;spage=1090;epage=1098;aulast=Guocell reprogramming; cell transplantation; hypoxia; neural progenitor cells; neurological function; parkinson’s disease; small molecule compounds; substantia nigra |
| spellingShingle | Yu Guo Yuan-Yuan Wang Ting-Ting Sun Jia-Jia Xu Pan Yang Cai-Yun Ma Wei-Jun Guan Chun-Jing Wang Gao-Feng Liu Chang-Qing Liu Neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of Parkinson’s disease in rats Neural Regeneration Research cell reprogramming; cell transplantation; hypoxia; neural progenitor cells; neurological function; parkinson’s disease; small molecule compounds; substantia nigra |
| title | Neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of Parkinson’s disease in rats |
| title_full | Neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of Parkinson’s disease in rats |
| title_fullStr | Neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of Parkinson’s disease in rats |
| title_full_unstemmed | Neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of Parkinson’s disease in rats |
| title_short | Neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of Parkinson’s disease in rats |
| title_sort | neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of parkinson s disease in rats |
| topic | cell reprogramming; cell transplantation; hypoxia; neural progenitor cells; neurological function; parkinson’s disease; small molecule compounds; substantia nigra |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=5;spage=1090;epage=1098;aulast=Guo |
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