Enhancing neural stem cell integration in the injured spinal cord through targeted PTEN modulation
Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks. Transplantation of neural stem cells holds promise to repair disrupted connections. Yet, ensuring the survival and integration of neural stem cells into the host neural circuit remains a formi...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2026-04-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | https://journals.lww.com/10.4103/NRR.NRR-D-24-00455 |
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| author | Simay Genişcan Hee Hwan Park Hyung Soon Kim Seokjin Yoo Hyunmi Kim Byeong Seong Jang Dong Hoon Hwang Kevin K Park Byung Gon Kim |
| author_facet | Simay Genişcan Hee Hwan Park Hyung Soon Kim Seokjin Yoo Hyunmi Kim Byeong Seong Jang Dong Hoon Hwang Kevin K Park Byung Gon Kim |
| author_sort | Simay Genişcan |
| collection | DOAJ |
| description | Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks. Transplantation of neural stem cells holds promise to repair disrupted connections. Yet, ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge. Here, we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation. We focused on phosphatase and tensin homolog (PTEN), a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration. By deleting Pten in mouse neural stem cells, we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture. Upon transplantation into injured spinal cords, Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution. To examine the potential influence of partial PTEN suppression, rat neural stem cells were treated with short hairpin RNA targeting PTEN, and the PTEN knockdown resulted in significant improvements in neurite growth, survival, and neurosphere motility in vitro. Transplantation of shPTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion. Moreover, PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter. These findings suggest that modifying intrinsic signaling pathways, such as PTEN, within neural stem cells could bolster their therapeutic efficacy, offering potential avenues for future regenerative strategies for spinal cord injury. |
| format | Article |
| id | doaj-art-9a4f4d3da4cb48c98802406bd4459e9e |
| institution | DOAJ |
| issn | 1673-5374 1876-7958 |
| language | English |
| publishDate | 2026-04-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj-art-9a4f4d3da4cb48c98802406bd4459e9e2025-08-20T02:44:28ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582026-04-012141586159410.4103/NRR.NRR-D-24-00455Enhancing neural stem cell integration in the injured spinal cord through targeted PTEN modulationSimay GenişcanHee Hwan ParkHyung Soon KimSeokjin YooHyunmi KimByeong Seong JangDong Hoon HwangKevin K ParkByung Gon KimSpinal cord injury results in permanent loss of neurological functions due to severance of neural networks. Transplantation of neural stem cells holds promise to repair disrupted connections. Yet, ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge. Here, we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation. We focused on phosphatase and tensin homolog (PTEN), a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration. By deleting Pten in mouse neural stem cells, we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture. Upon transplantation into injured spinal cords, Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution. To examine the potential influence of partial PTEN suppression, rat neural stem cells were treated with short hairpin RNA targeting PTEN, and the PTEN knockdown resulted in significant improvements in neurite growth, survival, and neurosphere motility in vitro. Transplantation of shPTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion. Moreover, PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter. These findings suggest that modifying intrinsic signaling pathways, such as PTEN, within neural stem cells could bolster their therapeutic efficacy, offering potential avenues for future regenerative strategies for spinal cord injury.https://journals.lww.com/10.4103/NRR.NRR-D-24-00455graft axon growthgraft survivalneural stem cellptenregenerationspinal cord injurytransplantation |
| spellingShingle | Simay Genişcan Hee Hwan Park Hyung Soon Kim Seokjin Yoo Hyunmi Kim Byeong Seong Jang Dong Hoon Hwang Kevin K Park Byung Gon Kim Enhancing neural stem cell integration in the injured spinal cord through targeted PTEN modulation Neural Regeneration Research graft axon growth graft survival neural stem cell pten regeneration spinal cord injury transplantation |
| title | Enhancing neural stem cell integration in the injured spinal cord through targeted PTEN modulation |
| title_full | Enhancing neural stem cell integration in the injured spinal cord through targeted PTEN modulation |
| title_fullStr | Enhancing neural stem cell integration in the injured spinal cord through targeted PTEN modulation |
| title_full_unstemmed | Enhancing neural stem cell integration in the injured spinal cord through targeted PTEN modulation |
| title_short | Enhancing neural stem cell integration in the injured spinal cord through targeted PTEN modulation |
| title_sort | enhancing neural stem cell integration in the injured spinal cord through targeted pten modulation |
| topic | graft axon growth graft survival neural stem cell pten regeneration spinal cord injury transplantation |
| url | https://journals.lww.com/10.4103/NRR.NRR-D-24-00455 |
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