Recent Publications
For a comprehensive list of our publications, please see our Google Scholar page.
Combined Transplantation of Mesenchymal Progenitor and Neural Stem Cells to Repair Cervical Spinal Cord Injury (2025)
In this study, we showed that intravenous transplantation of mesenchymal progenitor cells (MPCs) 24 hours after spinal cord injury enhanced early survival and oligodendrocyte differentiation of neural stem cells (NSCs) transplanted at day three, but not at day seven. We found that MPCs modulate early inflammatory signaling, creating a transiently favorable tissue environment for NSC integration and maturation. Our in vitro assays confirmed that MPCs significantly drive NSC-derived oligodendrocyte differentiation compared to NSC-only cultures. These findings emphasize the critical role of timing and combinatorial strategies in optimizing cellular therapies for spinal cord injury.
Efficacy of Deferoxamine Mesylate in Serum and Serum-Free Media: Adult Schwann Cell Survival Following Hydrogen Peroxide Induced Cell Death (2025)
Schwann cell (SC) transplantation for spinal cord injury faces challenges from ROS-induced oxidative stress, but this study shows that SCs survive well under serum-free conditions without deferoxamine mesylate (DFO) pretreatment. In serum-free environments, SCs exhibit strong nuclear Hif1α expression and upregulation of autophagy-related genes, suggesting an intrinsic pro-repair, pro-survival phenotype. By contrast, DFO improves SC survival only in serum-containing conditions, where oxidative stress is exacerbated. Overall, serum-free conditions inherently enhance SC resilience to oxidative damage by promoting hypoxic and autophagic pathways.
In this review, we discuss how IPSC-derived therapies have advanced the field of central nervous system regeneration by offering ethically and technically viable alternatives to embryonic stem cells. We highlight the multifaceted regenerative potential of iPSCs, capable of differentiating into diverse neural and glial subtypes, while also addressing challenges like unregulated differentiation, teratoma risk, immune rejection, and the need for optimized delivery strategies. We emphasize that successful clinical translation will depend on precise control over differentiation, graft integration, and immune modulation. Through this review, we aim to illuminate both the breakthroughs and remaining obstacles in using iPSC-derived therapies to promote endogenous CNS repair.
We present a combinatorial therapy for cervical spinal cord injury that includes a custom-engineered, injectable hydrogel and human induced pluripotent stem cell (iPSC)-derived deep cortical neurons. We designed a biomimetic hydrogel with a modular structure, allowing customization of the cell-adhesive peptide sequence and gel mechanical properties, which supported cell viability and neurite extension in vitro. Upon injection into a rat model of cervical spinal cord injury, the hydrogel biodegraded over six weeks without causing adverse reactions, and significantly enhanced the reproducibility of cell transplantation and integration compared to saline. Across three behavioral metrics, this therapy significantly improved sensorimotor function by six weeks post-transplantation. These results demonstrate the potential of a customized hydrogel-cell combination therapy to promote regeneration in the injured cervical spinal cord.
This chapter discusses the unique challenges and methodologies in tissue engineering for the nervous system, focusing on the peripheral and central nervous systems' intricate anatomical and cellular complexity. It emphasizes the critical role of selecting appropriate animal models for nervous tissue repair and highlights that most efforts have been directed towards promoting neurite outgrowth and nerve regeneration. Applications in neuroprotection and cellular reconstitution remain less explored, indicating a need for broader research focus within the field.
We demonstrate that transplantation of human induced pluripotent stem cells differentiated towards a deep cortical neuron lineage (iPSC-DCNs) into a rat model of cervical spinal cord injury (SCI) leads to robust regeneration of damaged neural circuits. We show that iPSC-DCNs integrate into the injured spinal cord, extend axons to distal targets, and reverse SCI-induced pathophysiology. Additionally, our results reveal that these cells promote significant regeneration of host supraspinal neural tracts and enhance sensorimotor function. This study represents a significant advancement in anatomical and functional recovery, showcasing the therapeutic potential of human stem cell-derived cortical neurons in SCI treatment.
We assessed the use of synthetic nerve guidance conduits (NGCs), comparing naturally derived materials with synthesized ones for treating peripheral nerve injuries (PNI). It introduces protein engineering as a promising method that combines the bioactivity of natural materials with the tunability and consistency of synthetic ones. A study with a recombinantly derived elastin-like protein (ELP) hydrogel used as an intraluminal filler in a rat model of sciatic nerve injury showed enhanced nerve regeneration, including tissue bridge formation between nerve stumps, myelinated axons, and improved muscle innervation, suggesting that ELP hydrogels could be an effective, reproducible alternative for peripheral nerve regeneration.
We extend our previous work by investigating the effects of Schwann cells (SCs) transduced with additional lentiviral vectors (LVs) expressing GDNF or NGF on axonal regeneration across a 1 cm peroneal nerve defect. We characterized the regenerating sensory and motor neurons using Fluorogold (FG) retrograde tracing 10 weeks post-surgery, comparing these grafts with intact nerves, autografts, acellular grafts, and SCs expressing LV-GFP. Notably, the LV-GDNF group showed significantly fewer labeled sensory neurons and complex fascicular morphology, suggesting axon trapping. The SC-NT-3 group demonstrated enhanced regeneration of sensory CGRP+ and IB4+ neurons, preferential regeneration of γ-motor neurons, and potential partial restoration of monosynaptic sensorimotor relays. Additionally, the proportion of NeuN-negative FG+ neurons was significantly higher in the SC-NT-3 group, indicating greater regeneration of specific motor neuron subtypes compared to other groups. These findings highlight the differential effects of various neurotrophic factors on the regeneration of sensory and motor neurons in peripheral nerve grafts.
We report a significant advancement in treating cervical spinal cord injuries using human induced pluripotent stem cells (iPSCs) differentiated towards a deep cortical neuron lineage. Transplanted into a rat model of spinal cord injury, these iPSC-derived cortical neurons not only integrated into the damaged spinal cord and extended axons to target areas but also reversed pathophysiology, promoted regeneration of severed host neural tracts, and notably improved sensorimotor functions. This study showcases a major shift in potential therapeutic outcomes for spinal cord injuries, demonstrating the effectiveness of stem cell-derived cortical neurons in anatomical and functional recovery beyond current models.
We review the interplay between proprioceptive sensory input and descending supraspinal projections in shaping spinal circuitry and locomotor behaviors, focusing on their mutual influence during development and after spinal cord injury. We discuss the developmental mechanisms underlying the formation of sensory-motor circuits and their interactions with local spinal interneurons. Additionally, we explore the competitive dynamics between proprioceptive and supraspinal inputs following spinal cord injury, highlighting how these interactions impact circuit reorganization and functional recovery.
