Safety and efficacy evaluation of intracerebroventricular human neural stem cell transplantation in SOD1 mice as a novel approach for ALS
Abstract Background Neural stem cell (NSC) transplantation holds promising therapeutic potential for neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). However, pre-clinical studies and early-phase clinical trials have faced challenges hindering the effective clinical translation...
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| Language: | English |
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BMC
2025-05-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06529-9 |
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| author | Ivan Lombardi Clelia Ferrero Edvige Vulcano Daniela Maria Rasà Maurizio Gelati Diego Pastor Rose Mary Carletti Silvia de la Morena Daniela Celeste Profico Sabrina Longobardi Elisa Lazzarino Elisa Perciballi Jessica Diana Rosati Salvador Martinez Alessandro Vercelli Angelo Luigi Vescovi Marina Boido Daniela Ferrari |
| author_facet | Ivan Lombardi Clelia Ferrero Edvige Vulcano Daniela Maria Rasà Maurizio Gelati Diego Pastor Rose Mary Carletti Silvia de la Morena Daniela Celeste Profico Sabrina Longobardi Elisa Lazzarino Elisa Perciballi Jessica Diana Rosati Salvador Martinez Alessandro Vercelli Angelo Luigi Vescovi Marina Boido Daniela Ferrari |
| author_sort | Ivan Lombardi |
| collection | DOAJ |
| description | Abstract Background Neural stem cell (NSC) transplantation holds promising therapeutic potential for neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). However, pre-clinical studies and early-phase clinical trials have faced challenges hindering the effective clinical translation of this approach. Crucial hurdles include the side-effects of prolonged immunosuppression, concerns regarding cell origin and transplantation dosage, identification of the most appropriate therapeutic window, and invasiveness of surgical procedures. Here, we assessed the safety and efficacy of intracerebroventricular (ICV) hNSC transplantation as a novel and possibly more effective experimental approach for ALS. Methods We evaluated the safety of administering up to 1 × 106 hNSCs in immunodeficient mice and assessed their potential efficacy in reducing ALS hallmarks employing the SOD1G93A mouse model. Both transient (15 days) and prolonged immunosuppression regimens, at low (15 mg/kg) and high (30 mg/kg) doses, were tested along with two different cell dosages (3 × 105 and 1 × 106). Results Our study suggests that: (i) a bilateral ICV transplantation of 1 × 106 hNSCs is safe and non-tumorigenic in immunodeficient hosts; (ii) sustained and high-dose immunosuppression is essential for ensuring cell survival in immunocompetent SOD1G93A mice; and (iii) hNSCs may delay motor symptom progression and reduce spinal cord microgliosis in SOD1G93A mice when administered in the lateral ventricles under prolonged high-dose (30 mg/kg) immunosuppression. Conclusions ICV transplantation of hNSCs emerges as a safe and promising strategy for ALS, demonstrating potential to delay motor decline and reduce spinal cord microgliosis. However, sustained high-dose immunosuppression is crucial for therapeutic efficacy, emphasizing the need for further optimization to overcome translational challenges and achieve durable clinical benefits. |
| format | Article |
| id | doaj-art-ff1472786cf34a67b0014dc78c796b0e |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-ff1472786cf34a67b0014dc78c796b0e2025-08-20T02:15:07ZengBMCJournal of Translational Medicine1479-58762025-05-0123111910.1186/s12967-025-06529-9Safety and efficacy evaluation of intracerebroventricular human neural stem cell transplantation in SOD1 mice as a novel approach for ALSIvan Lombardi0Clelia Ferrero1Edvige Vulcano2Daniela Maria Rasà3Maurizio Gelati4Diego Pastor5Rose Mary Carletti6Silvia de la Morena7Daniela Celeste Profico8Sabrina Longobardi9Elisa Lazzarino10Elisa Perciballi11Jessica Diana Rosati12Salvador Martinez13Alessandro Vercelli14Angelo Luigi Vescovi15Marina Boido16Daniela Ferrari17School of Medicine and Surgery, University of Milano-BicoccaNeuroscience Institute Cavalieri Ottolenghi (N.I.C.O.), University of TurinDepartment of Biotechnology and Biosciences, University of Milano-BicoccaNeuroscience Institute Cavalieri Ottolenghi (N.I.C.O.), University of TurinProduction Unit of Advanced Therapies (UPTA), Fondazione IRCCS Casa Sollievo della SofferenzaSport Research Centre, Miguel Hernández UniversityProduction Unit of Advanced Therapies (UPTA), Fondazione IRCCS Casa Sollievo della SofferenzaNeuroscience Institute Cavalieri Ottolenghi (N.I.C.O.), University of TurinProduction Unit of Advanced Therapies (UPTA), Fondazione IRCCS Casa Sollievo della SofferenzaDepartment of Biotechnology and Biosciences, University of Milano-BicoccaNeuroscience Institute Cavalieri Ottolenghi (N.I.C.O.), University of TurinDepartment of Biotechnology and Biosciences, University of Milano-BicoccaCellular Reprogramming Unit, Fondazione IRCCS Casa Sollievo della SofferenzaInstituto de Neurociencias de Alicante (UMH-CSIC), Universidad Miguel HernandezNeuroscience Institute Cavalieri Ottolenghi (N.I.C.O.), University of TurinFaculty of Medicine, Link Campus UniversityNeuroscience Institute Cavalieri Ottolenghi (N.I.C.O.), University of TurinDepartment of Biotechnology and Biosciences, University of Milano-BicoccaAbstract Background Neural stem cell (NSC) transplantation holds promising therapeutic potential for neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). However, pre-clinical studies and early-phase clinical trials have faced challenges hindering the effective clinical translation of this approach. Crucial hurdles include the side-effects of prolonged immunosuppression, concerns regarding cell origin and transplantation dosage, identification of the most appropriate therapeutic window, and invasiveness of surgical procedures. Here, we assessed the safety and efficacy of intracerebroventricular (ICV) hNSC transplantation as a novel and possibly more effective experimental approach for ALS. Methods We evaluated the safety of administering up to 1 × 106 hNSCs in immunodeficient mice and assessed their potential efficacy in reducing ALS hallmarks employing the SOD1G93A mouse model. Both transient (15 days) and prolonged immunosuppression regimens, at low (15 mg/kg) and high (30 mg/kg) doses, were tested along with two different cell dosages (3 × 105 and 1 × 106). Results Our study suggests that: (i) a bilateral ICV transplantation of 1 × 106 hNSCs is safe and non-tumorigenic in immunodeficient hosts; (ii) sustained and high-dose immunosuppression is essential for ensuring cell survival in immunocompetent SOD1G93A mice; and (iii) hNSCs may delay motor symptom progression and reduce spinal cord microgliosis in SOD1G93A mice when administered in the lateral ventricles under prolonged high-dose (30 mg/kg) immunosuppression. Conclusions ICV transplantation of hNSCs emerges as a safe and promising strategy for ALS, demonstrating potential to delay motor decline and reduce spinal cord microgliosis. However, sustained high-dose immunosuppression is crucial for therapeutic efficacy, emphasizing the need for further optimization to overcome translational challenges and achieve durable clinical benefits.https://doi.org/10.1186/s12967-025-06529-9Cell therapyNeural stem cellsTransplantationALSIntracerebroventricularSOD1 model |
| spellingShingle | Ivan Lombardi Clelia Ferrero Edvige Vulcano Daniela Maria Rasà Maurizio Gelati Diego Pastor Rose Mary Carletti Silvia de la Morena Daniela Celeste Profico Sabrina Longobardi Elisa Lazzarino Elisa Perciballi Jessica Diana Rosati Salvador Martinez Alessandro Vercelli Angelo Luigi Vescovi Marina Boido Daniela Ferrari Safety and efficacy evaluation of intracerebroventricular human neural stem cell transplantation in SOD1 mice as a novel approach for ALS Journal of Translational Medicine Cell therapy Neural stem cells Transplantation ALS Intracerebroventricular SOD1 model |
| title | Safety and efficacy evaluation of intracerebroventricular human neural stem cell transplantation in SOD1 mice as a novel approach for ALS |
| title_full | Safety and efficacy evaluation of intracerebroventricular human neural stem cell transplantation in SOD1 mice as a novel approach for ALS |
| title_fullStr | Safety and efficacy evaluation of intracerebroventricular human neural stem cell transplantation in SOD1 mice as a novel approach for ALS |
| title_full_unstemmed | Safety and efficacy evaluation of intracerebroventricular human neural stem cell transplantation in SOD1 mice as a novel approach for ALS |
| title_short | Safety and efficacy evaluation of intracerebroventricular human neural stem cell transplantation in SOD1 mice as a novel approach for ALS |
| title_sort | safety and efficacy evaluation of intracerebroventricular human neural stem cell transplantation in sod1 mice as a novel approach for als |
| topic | Cell therapy Neural stem cells Transplantation ALS Intracerebroventricular SOD1 model |
| url | https://doi.org/10.1186/s12967-025-06529-9 |
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