Review
Beyond Transplantation: Engineering Neural Cell Therapies and Combination Strategies for Spinal Cord Repair
Brain sciences, v 16(1), p113
01 Jan 2026
PMID: 41594834
Abstract
Spinal cord injury (SCI) remains one of the most formidable challenges in regenerative medicine, often resulting in permanent loss of motor, sensory, and autonomic function. Cell-based therapies offer a promising path toward repair by providing donor neurons and glia capable of integrating into host circuits, modulating the injury environment, and restoring function. Early studies employing fetal neural tissue and neural progenitor cells (NPCs) have demonstrated proof-of-principle for survival, differentiation, and synaptic integration. More recently, pluripotent stem cell (PSC)-derived donor populations and engineered constructs have expanded the therapeutic repertoire, enabling precise specification of interneuron subtypes, astrocytes, and oligodendrocytes tailored to the injured spinal cord. Advances in genetic engineering, including CRISPR-based editing, trophic factor overexpression, and immune-evasive modifications, are giving rise to next-generation donor cells with enhanced survival and controllable integration. At the same time, biomaterials, pharmacological agents, activity-based therapies, and neuromodulation strategies are being combined with transplantation to overcome barriers and promote long-term recovery. In this review, we summarize progress in designing and engineering donor cells and tissues for SCI repair, highlight how combination strategies are reshaping the therapeutic landscape, and outline opportunities for next-generation approaches. Together, these advances point toward a future in which tailored, multimodal cell-based therapies achieve consistent and durable restoration of spinal cord function.
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Details
- Title
- Beyond Transplantation: Engineering Neural Cell Therapies and Combination Strategies for Spinal Cord Repair
- Creators
- Lyandysha Zholudeva - Gladstone InstitutesDennis Bourbeau - Louis Stokes Cleveland VA Medical CenterAdam Hall - Drexel UniversitySpruance VictoriaOgbolu VictorQiang LiangSakiyama-Elbert ShellyMichael Lane - Drexel University
- Publication Details
- Brain sciences, v 16(1), p113
- Publisher
- MDPI; Basel
- Number of pages
- 35
- Grant note
- alsFINDaCURE and HOP on a CUREAlzheimer's Association: 24AARG-D-1191264 Lisa Dean Moseley FoundationCURE program from Drexel University College of Medicine SAP: 4100083087 California Institute for Regenerative Medicine: DISC2-14180 National Institutes of Health: R01NS104291, R01NS115977
Research relevant to this Review was supported by grants from California Institute for Regenerative Medicine DISC2-14180 (L.V.Z.); Lisa Dean Moseley Foundation (M.A.L., L.Q.); National Institutes of Health R01NS104291 (M.A.L.), R01NS115977 (L.Q.); the alsFINDaCURE and HOP on a CURE (L.Q.); the Alzheimer's Association, 24AARG-D-1191264 (L.Q.); the CURE program from Drexel University College of Medicine SAP: 4100083087 (L.Q.).
- Resource Type
- Review
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:001670703700001
- Other Identifier
- 991022155314304721