Beyond Transplantation: Engineering Neural Cell Therapies and Combination Strategies for Spinal Cord Repair

Zholudeva, Lyandysha V.; Bourbeau, Dennis; Hall, Adam; Spruance, Victoria; Ogbolu, Victor; Qiang, Liang; Sakiyama-Elbert, Shelly; Lane, Michael A.

doi:10.3390/brainsci16010113

Open AccessReview

Beyond Transplantation: Engineering Neural Cell Therapies and Combination Strategies for Spinal Cord Repair

by

Lyandysha V. Zholudeva

^1,*

,

Dennis Bourbeau

^2,3

,

Adam Hall

⁴,

Victoria Spruance

⁵,

Victor Ogbolu

⁴

,

Liang Qiang

⁴,

Shelly Sakiyama-Elbert

⁶ and

Michael A. Lane

^4,*

¹

Gladstone Institutes, San Francisco, CA 94158, USA

²

Department of Physical Medicine and Rehabilitation, MetroHealth Medical Center, Cleveland, OH 44109, USA

³

Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, OH 44106, USA

⁴

Department of Neurobiology and Anatomy, Drexel University, Philadelphia, PA 19129, USA

⁵

Spruance and Associates, Jacksonville, FL 32207, USA

⁶

Department of Bioengineering, University of Washington, Seattle, WA 98195, USA

^*

Authors to whom correspondence should be addressed.

Brain Sci. 2026, 16(1), 113; https://doi.org/10.3390/brainsci16010113

Submission received: 18 September 2025 / Revised: 7 January 2026 / Accepted: 13 January 2026 / Published: 21 January 2026

(This article belongs to the Special Issue Spinal Cord Injury)

Download

Browse Figures

Versions Notes

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.

Keywords: cell transplantation; cell engineering; combination therapy; spinal cord injury

Share and Cite

MDPI and ACS Style

Zholudeva, L.V.; Bourbeau, D.; Hall, A.; Spruance, V.; Ogbolu, V.; Qiang, L.; Sakiyama-Elbert, S.; Lane, M.A. Beyond Transplantation: Engineering Neural Cell Therapies and Combination Strategies for Spinal Cord Repair. Brain Sci. 2026, 16, 113. https://doi.org/10.3390/brainsci16010113

AMA Style

Zholudeva LV, Bourbeau D, Hall A, Spruance V, Ogbolu V, Qiang L, Sakiyama-Elbert S, Lane MA. Beyond Transplantation: Engineering Neural Cell Therapies and Combination Strategies for Spinal Cord Repair. Brain Sciences. 2026; 16(1):113. https://doi.org/10.3390/brainsci16010113

Chicago/Turabian Style

Zholudeva, Lyandysha V., Dennis Bourbeau, Adam Hall, Victoria Spruance, Victor Ogbolu, Liang Qiang, Shelly Sakiyama-Elbert, and Michael A. Lane. 2026. "Beyond Transplantation: Engineering Neural Cell Therapies and Combination Strategies for Spinal Cord Repair" Brain Sciences 16, no. 1: 113. https://doi.org/10.3390/brainsci16010113

APA Style

Zholudeva, L. V., Bourbeau, D., Hall, A., Spruance, V., Ogbolu, V., Qiang, L., Sakiyama-Elbert, S., & Lane, M. A. (2026). Beyond Transplantation: Engineering Neural Cell Therapies and Combination Strategies for Spinal Cord Repair. Brain Sciences, 16(1), 113. https://doi.org/10.3390/brainsci16010113

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Beyond Transplantation: Engineering Neural Cell Therapies and Combination Strategies for Spinal Cord Repair

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI