Enhanced neurogenesis after ischemic stroke: The interplay between endogenous and exogenous stem cells
Ischemic stroke is a significant global health crisis, frequently resulting in disability or death, with limited therapeutic interventions available. Although various intrinsic reparative processes are initiated within the ischemic brain, these mechanisms are often insufficient to restore neuronal f...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2026-01-01
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| Series: | Neural Regeneration Research |
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| Online Access: | https://journals.lww.com/10.4103/NRR.NRR-D-24-00879 |
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| author | Ruxu Geng Yuhe Wang Renzhi Wang Jun Wu Xinjie Bao |
| author_facet | Ruxu Geng Yuhe Wang Renzhi Wang Jun Wu Xinjie Bao |
| author_sort | Ruxu Geng |
| collection | DOAJ |
| description | Ischemic stroke is a significant global health crisis, frequently resulting in disability or death, with limited therapeutic interventions available. Although various intrinsic reparative processes are initiated within the ischemic brain, these mechanisms are often insufficient to restore neuronal functionality. This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option. This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events, with focus on the impact of stem cell-based therapies on neural stem cells. Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-to-cell contact and through the secretion of growth factors and exosomes. Additionally, implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called “biobridges.” Furthermore, xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects, thereby supporting endogenous neuroregeneration. Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment, we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types. These approaches include: (1) co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis; (2) synergistic administration of stem cells and their exosomes to amplify paracrine effects; and (3) integration of stem cells within hydrogels, which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits. This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke. |
| format | Article |
| id | doaj-art-e8cbd018c3b840cfbfbe01c2c428f788 |
| institution | DOAJ |
| issn | 1673-5374 1876-7958 |
| language | English |
| publishDate | 2026-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj-art-e8cbd018c3b840cfbfbe01c2c428f7882025-08-20T03:07:51ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582026-01-0121121222310.4103/NRR.NRR-D-24-00879Enhanced neurogenesis after ischemic stroke: The interplay between endogenous and exogenous stem cellsRuxu GengYuhe WangRenzhi WangJun WuXinjie BaoIschemic stroke is a significant global health crisis, frequently resulting in disability or death, with limited therapeutic interventions available. Although various intrinsic reparative processes are initiated within the ischemic brain, these mechanisms are often insufficient to restore neuronal functionality. This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option. This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events, with focus on the impact of stem cell-based therapies on neural stem cells. Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-to-cell contact and through the secretion of growth factors and exosomes. Additionally, implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called “biobridges.” Furthermore, xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects, thereby supporting endogenous neuroregeneration. Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment, we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types. These approaches include: (1) co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis; (2) synergistic administration of stem cells and their exosomes to amplify paracrine effects; and (3) integration of stem cells within hydrogels, which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits. This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.https://journals.lww.com/10.4103/NRR.NRR-D-24-00879brain-derived neurotrophic factorendogenous neuroregenerationexosomeshydrogelsischemic strokemesenchymal stem cellsneural stem cellsneurogenesisstem cell transplantation |
| spellingShingle | Ruxu Geng Yuhe Wang Renzhi Wang Jun Wu Xinjie Bao Enhanced neurogenesis after ischemic stroke: The interplay between endogenous and exogenous stem cells Neural Regeneration Research brain-derived neurotrophic factor endogenous neuroregeneration exosomes hydrogels ischemic stroke mesenchymal stem cells neural stem cells neurogenesis stem cell transplantation |
| title | Enhanced neurogenesis after ischemic stroke: The interplay between endogenous and exogenous stem cells |
| title_full | Enhanced neurogenesis after ischemic stroke: The interplay between endogenous and exogenous stem cells |
| title_fullStr | Enhanced neurogenesis after ischemic stroke: The interplay between endogenous and exogenous stem cells |
| title_full_unstemmed | Enhanced neurogenesis after ischemic stroke: The interplay between endogenous and exogenous stem cells |
| title_short | Enhanced neurogenesis after ischemic stroke: The interplay between endogenous and exogenous stem cells |
| title_sort | enhanced neurogenesis after ischemic stroke the interplay between endogenous and exogenous stem cells |
| topic | brain-derived neurotrophic factor endogenous neuroregeneration exosomes hydrogels ischemic stroke mesenchymal stem cells neural stem cells neurogenesis stem cell transplantation |
| url | https://journals.lww.com/10.4103/NRR.NRR-D-24-00879 |
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