About

Armin Blesch is a Professor In Residence in the Neurosciences School at UC San Diego, located at 9500 Gilman Drive, La Jolla, CA. He earned his PhD in Genetics and Neurology from the University of Wurzburg in 1995. His research focuses on spinal cord injury, neural regeneration, and pain mechanisms, utilizing various innovative approaches such as neural stem cell grafting, hydrogel scaffolds, electrical stimulation, and gene transfer techniques. Blesch has contributed significantly to understanding axonal regeneration, neurorepair, and the development of therapies for spinal cord injuries, with numerous publications derived from extensive research activities and funded projects. His work aims to promote neurorestoration and functional recovery after spinal cord injury through targeted tissue engineering, molecular, and cellular strategies.

Research topics

• Cell biology
• Biology
• Medicine
• Neuroscience
• Surgery
• Anatomy
• Pathology
• Internal medicine

Selected publications

• ID3-depleted human induced pluripotent stem cell–derived neural stem/progenitor cells promote neurorepair

  Neural Regeneration Research · 2025-09-03 · 1 citations

  articleOpen access

  Abstract Human induced pluripotent stem cell–derived neural stem/progenitor cells are used in cell-replacement and regenerative therapeutic strategies after traumatic central nervous system injury. Traumatic injury alters the host microenvironment, which in turn affects the functionality of transplanted human neural stem/ progenitor cells and potentially limits their benefits for neurorepair. However, the underlying mechanisms through which the host environment alters the fate and functionality of transplanted human neural stem/progenitor cells remain poorly understood. Here, we showed that massive deposition of blood-derived fibrinogen in a mouse model of spinal cord injury contributed to an altered lesion environment. Fibrinogen promoted human neural stem/progenitor cell differentiation into reactive astrocytes by activating the BMP receptor signaling pathway and inducing of the transcriptional regulator inhibitor of DNA binding 3. ID3 -depleted human neural stem/progenitor cells, generated by CRISPR/Cas9-mediated genome editing, reduced astrocyte formation in response to astrogenic stimuli. Instead, ID3 -depleted human neural stem/progenitor cells had a bipolar, immature glial progenitor cell phenotype. These modified cells secreted extracellular vesicles with a distinct miRNA profile that enhanced neurite outgrowth. We conclude that targeting inhibitor of DNA binding 3 in human neural stem/progenitor cells can beneficially modulate their functionality and cell fate in the injured central nervous system toward glial progenitor cells, potentially enhancing their capacity to promote central nervous system repair.

  PublisherDOI

• Lessons Learned and Recommendations from a SCOPE Spinal Cord Injury Neurorestorative Clinical Trials Update

  Neurotrauma Reports · 2025-01-01 · 2 citations

  reviewOpen access

  considerations, prioritizing novelty and a focus on neurorestorative approaches. The sessions featured 13 speakers, covering 4 in-preparation, 4 in-progress, and 4 recently completed trials. In addition to in-person attendance, individuals worldwide viewed a live stream of the presentations. Approximately 1600 participants, comprising clinicians, researchers, industry stakeholders, foundations, and individuals with lived experiences, engaged in the CTU through both in-person and virtual channels. Presentations represented a variety of approaches, including drug, biological, and device-based therapeutics. This summary provides high-level summaries of the trials presented and the resulting discussions including lessons learned. Rather than recapitulating published data, the presentations and discussions emphasized the novelty and strengths of each trial, practical aspects of translation, and lessons learned. Throughout the day, several discussion themes surfaced. These included reflections on the suitability of outcome measures and the distinction between statistically or clinically meaningful effects and meaningful changes in quality of life. Additional topics included novel trial designs, selection of inclusion criteria, recognizing the indispensable role of rehabilitation, tailoring approaches to individual needs, the importance of integrating lived experience, and emphasizing the importance of establishing robust pre-clinical data packages before venturing into clinical translation. Importantly, strategic directives are summarized to address these challenges, focusing resources and efforts to steer forthcoming trials effectively.

  PublisherDOI

• Dosing parameters for grafting human neural stem cells into sites of spinal cord injury

  Experimental Neurology · 2025-09-22 · 1 citations

  article
  PublisherDOI

• Neural Stem Cells for Spinal Cord Injury

  Translational Neuroscience · 2025-01-01

  book-chapterOpen access

  Neural stem cells (NSCs) are potentially attractive cell sources for repair of injured spinal cord circuits. They can be derived from embryonic central nervous system tissue, pluripotent stem cells, induced pluripotent stem cells, or trans-differentiated cells. Recent studies demonstrate that NSCs or neural progenitor cells (NPCs) can survive grafting into sites of severe spinal cord injury (SCI), differentiate into neurons and glia, and extend very large numbers of axons over substantial distances for connectivity with host neurons below sites of injury. Reciprocally, host axons regenerate into the NSC/NPC grafts and form synaptic connections with graft-derived neurons. Therefore, NSC/NPC graft-derived neurons serve as neuronal relays that re-establish neural transmission across the lesion site, improving functional outcomes even after severe SCI. These findings are confirmed in the larger primate system, paving a translational path for clinical application.

  PublisherDOI

• An improved method for generating human spinal cord neural stem cells

  Experimental Neurology · 2024-04-15 · 9 citations

  article
  PublisherDOI

• Alginate hydrogel cross-linked by Ca2+ to promote spinal cord neural stem/progenitor cell differentiation and functional recovery after a spinal cord injuryhh

  Regenerative Biomaterials · 2022-01-01 · 26 citations

  articleOpen access

  Abstract Alginate capillary hydrogels seeded with differentiated cells can fill the lesion cavity and promote axonal regeneration after grafting into the injured spinal cord. Neural stem/progenitor cells (NSPCs) can potentially repair the spinal cord; however, effects of alginate hydrogels (AHs) on NSPCs remain unknown. In this study, we fabricated AHs cross-linked by Ca2+ and seeded hydrogels with rat embryonic day 14 NSPCs. Immunocytochemistry and electron microscopy show that NSPCs survive, proliferate and differentiate into neurons in vitro within the capillaries. After transplantation into an acute T8 complete spinal cord transection site in adult rats, approximately one-third (38.3%) of grafted cells survive and differentiate into neurons (40.7%), astrocytes (26.6%) and oligodendrocytes (28.4%) at 8 weeks post-grafting. NSPCs promote the growth of host axons within the capillaries in a time-dependent manner. Host axons make synapse-like contacts with NSPC-derived neurons within the hydrogel channels, and graft-derived axons extend into the host white and gray matter making putative synapses. This is paralleled by improved electrophysiological conductivity across the lesion and partial hindlimb locomotor recovery.

  PublisherOA PDFDOI

• Neural Stem Cells: Promoting Axonal Regeneration and Spinal Cord Connectivity

  Cells · 2021 · 66 citations

  • Neuroscience
  • Medicine
  • Biology

  Spinal cord injury (SCI) leads to irreversible functional impairment caused by neuronal loss and the disruption of neuronal connections across the injury site. While several experimental strategies have been used to minimize tissue damage and to enhance axonal growth and regeneration, the corticospinal projection, which is the most important voluntary motor system in humans, remains largely refractory to regenerative therapeutic interventions. To date, one of the most promising pre-clinical therapeutic strategies has been neural stem cell (NSC) therapy for SCI. Over the last decade we have found that host axons regenerate into spinal NSC grafts placed into sites of SCI. These regenerating axons form synapses with the graft, and the graft in turn extends very large numbers of new axons from the injury site over long distances into the distal spinal cord. Here we discuss the pathophysiology of SCI that makes the spinal cord refractory to spontaneous regeneration, the most recent findings of neural stem cell therapy for SCI, how it has impacted motor systems including the corticospinal tract and the implications for sensory feedback.

  PublisherOA PDFDOI

• Anisotropic Alginate Hydrogels Promote Axonal Growth across Chronic Spinal Cord Transections after Scar Removal

  ACS Biomaterials Science & Engineering · 2020 · 30 citations

  • Medicine
  • Anatomy
  • Neuroscience

  We have previously reported that cell-seeded alginate hydrogels (AHs) with anisotropic capillaries can restore the continuity of the spinal cord and support axonal regeneration in a rat model of acute partial spinal cord transection. Whether similar effects can be found after transplantation into sites of complete chronic spinal cord transections without additional growth-promoting stimuli has not been investigated. We therefore implanted AHs into the cavity of a chronic thoracic transection following scar resection (SR) 4 weeks postinjury and examined electrophysiological and functional recovery as well as regeneration of descending and ascending projections within and beyond the AH scaffold up to 3 months after engraftment. Our results indicate that both electrophysiological conductivity and locomotor function are significantly improved after AH engraftment. SR transiently impairs locomotor function immediately after surgery but does not affect long-term outcomes. Histological analysis shows numerous host cells migrating into the scaffold channels and a reduction of fibroglial scaring around the lesion by AH grafts. In contrast to corticospinal axons, raphaespinal and propriospinal descending axons and ascending sensory axons regenerate throughout the scaffolds and extend into the distal host parenchyma. These results further support the pro-regenerative properties of AHs and their therapeutic potential for chronic SCI in combination with other strategies to improve functional outcomes after spinal cord injury.

  PublisherDOI

• Targeted tissue engineering: hydrogels with linear capillary channels for axonal regeneration after spinal cord injury

  Neural Regeneration Research · 2018-01-01 · 9 citations

  articleOpen access1st authorCorresponding

  Spinal cord injury (SCI) frequently results in the permanent loss of function below the level of injury due to the failure of axonal regeneration in the adult mammalian central nervous system (CNS). The limited intrinsic growth capacity of adult neurons, a lack of growth-promoting factors and the multifactorial inhibitory microenvironment around the lesion site contribute to the lack of axonal regeneration. Strategies such as transplantation of cells, delivery of bioactive compounds and gene transfer have been investigated as a means to promote axonal regrowth through the lesion, to form new synaptic connections and to improve functional outcomes. Although growth of some axonal populations can be robustly enhanced by cellular implants alone or in combination with neurotrophic factors, axons usually extend in random orientation and even reverse growth direction in the lesion site (Figure 1A) (Gros et al., 2010; Günther et al., 2015). Thus, regenerating axons often fail to approach the distal edge of the lesion site, a pre-requisite for proper contact with spared host neurons. The lack of a 3-dimensional organization in the injury site is therefore an additional barrier for successful axonal bridging. Two approaches, physical guidance through structured scaffolds and chemical guidance by growth factor gradients, have emerged as potential means to provide directional cues for axonal growth through the lesion.Figure 1: Schematic of linear guidance of axonal growth by biomaterials containing a capillary channel structure filled with supporting cells.(A) Axons regenerate robustly into the lesion implanted with a suitable cellular graft, but growth is randomly oriented rather than extending in rostrocaudal direction toward the distal host parenchyma. (B) Transplantation of an anisotropic biomaterial can effectively fill the lesion cavity and direct a small number of axons to grow in a linear pattern within channels. (C) Linear axonal growth is enhanced when channels contain suitable cells increasing the number of regrowing axons that approach the distal graft/host interface allowing a few axons to re-enter the distal host spinal cord. (D) Additional gradients of neurotrophic factors generated by viral gene transfer and injections of suitable cells such as Schwann cells into the distal spinal cord promotes axonal growth across the distal host/graft interface.Scaffolds with linear channels: Advances in tissue engineering and biomaterials have provided promising leads for spinal cord repair. Biomaterials with high bio-compatibility and low toxicity can either be chemically synthesized or derived from natural polymers. After engraftment into sites of SCI, biomaterials can bridge the lesion cavity to restore continuity of the spinal cord. By adjusting the chemical and physical conditions during gelation, hydrogel scaffolds consisting of porous chambers, linear channels or aligned fibers can be fabricated. The internal structure can serve as a conduit to physically guide axon growth across the lesion, reduce contact of regenerating axons to the inhibitory microenvironment and act as a vehicle for cells and bioactive factors, which in turn create a permissive microenvironment for axonal growth (Figure 1B). Arrangement of cells in parallel channels may also contribute to axon orientation. Cells and blood vessels that are organized in distinct channels attract axons to sprout along the linear pores (Moore et al., 2006). For example, transplantation of freeze-dried agarose scaffolds or alginate hydrogels composed of uniaxial channels stimulate and guide axonal growth in a linear fashion after SCI (Stokols and Tuszynski, 2006; Günther et al., 2015). Cell filling and growth factors enhance axon growth in hydrogel channels: In most studies, biological effects of biomaterials without additional manipulations are limited following transplantation to the injured spinal cord despite a delicately fabricated microarchitecture. Therefore, biomaterials have frequently been combined with cells to improve morphological and functional outcomes. Biomaterials can provide a matrix for cell adhesion, and enhance cell survival as well as migration. In addition, cells that are co-transplanted within a scaffold can interact with the surrounding host tissue and increase axon growth into and beyond the graft/host border, a major obstacle for long-distance axonal regeneration (Figure 1C). As biomaterials effectively fill portions of the lesion cavity, the number of cells required for transplantation also decreases. This is particularly important for clinical translation and more extended lesions when large cell numbers that might be difficult to obtain are needed. Several cell types used for transplantation in animal models of SCI have been examined in combination with different biomaterials. These include studies using poly(lactic-co-glycolic acid) (PLGA) scaffolds composed of multiple channels together with Schwann cells (SCs), templated agarose scaffolds with bone marrow stromal cells (BMSCs) and alginate hydrogels with BMSC- or SC-filled channels. In PLGA scaffolds, axons were found to grow throughout the full extent of channels containing SCs but not in channels without SCs (Moore et al., 2006). In templated agarose scaffolds, oriented axonal growth in a highly linear topography throughout the channels was demonstrated when channels were pre-loaded with BMSCs and overexpressing brain derived neurotrophic factor (BDNF) robustly increased axon density within the scaffold (Stokols et al., 2006). Similarly, channels in templated agarose scaffolds seeded with neurotrophin-3 expressing BMSCs facilitated axonal growth towards the distal aspect of the graft, in comparison to animals that were grafted with cell suspensions without agarose scaffolds (Gros et al., 2010). As in studies with agarose scaffolds, BMSCs expressing BDNF enhanced axonal regeneration into channels of alginate hydrogels. However, axonal regeneration generally decreases in the central portion of hydrogel implants and axonal extension into the distal host spinal cord tissue was not observed (Günther et al., 2015). Influences of hydrogel channel diameter: The channel diameter of multi-channel biomaterials used in most studies ranged from 200 μm to 600 μm. In contrast to other techniques, alginate hydrogels with smaller anisotropic channels can be easily fabricated by diffusion of divalent cations through an alginate solution (Prang et al., 2006). Ranging from 10 μm to 100 μm, channel diameters depend on the cations utilized to cross-link alginate polymers (Pawar et al., 2015). In vitro cultures of neonatal cortex, spinal cord or dorsal root ganglia on alginate hydrogels have shown that the density of axon growth into the hydrogel positively correlates with the diameter of channels. In contrast, the linear orientation of axons diminishes with increasing channel diameter (Pawar et al., 2015). Other aspects that can be affected by microchannel diameter within the scaffold include the number and type of cells migrating into channels and newly formed blood vessels that occupy part of the channel lumen available for axonal regeneration. The influence of channel diameter in anisotropic alginate hydrogels seeded with BMSCs was recently evaluated in a cervical spinal cord hemisection lesion. Comparing channels with 41 μm (cross-linked by Sr2+) to 64 μm (cross-linked by Zn2+) diameter, axonal growth was supported throughout the lesion and the 50% difference in channel diameter did not influence axon density. While axon growth was overall oriented in a linear pattern irrespective of the diameter of hydrogel channels and similar to that observed in intact white matter of the spinal cord, even this small increase in channel diameter resulted in a measurable decrease in linear axonal orientation (Günther et al., 2015). Tissue integration of hydrogels and axonal bridging: Similar to transplantation studies with other biomaterials (Gros et al., 2010), one major obstacle impeding axonal growth beyond an alginate hydrogel is the graft/host interface. Host cells including astrocytes and fibroblasts that generate a myriad of inhibitors respond to the lesion and impede axon extension (Günther et al., 2015; Liu et al., 2017). To overcome the inhibitory environment, neurotrophin gradients extending from the adjacent host spinal cord into the graft can shift the balance from inhibition to growth promotion and induce some longer-distance axonal regeneration (Taylor et al., 2006). Degradation of inhibitors by enzymes such as chondroitinase, or modification of the density of the barrier to allow axon penetration have also shown success in combination with biomaterial implants (reviewed in Günther et al., 2016). In addition, SCs, currently under investigation in an FDA-approved clinical trial in SCI can improve the host-graft continuity. SCs can modify the interface to become more permissive for axonal growth by intermingling with astrocytic processes of the glial scar (Williams et al., 2015). Recent studies using a combination of alginate hydrogels with SCs demonstrate that axons can extend throughout the full length of channels without a decline in the number of axons in the central portion of the scaffold. While axonal growth is enhanced by BDNF delivered via viral gene transfer into the caudal tissue, this chemotropic gradient beyond the lesion was not sufficient for axons to bridge the lesion site. Only when SCs are co-injected into the caudal spinal cord, regrowing axons penetrate the caudal interface and extend into the host parenchyma (Figure 1D) (Liu et al., 2017). These findings further highlight the importance of the biomaterial/host interface and the critical role of barriers immediately surrounding the scaffold for successful axonal regeneration. Glial fibrillary acid protein (GFAP)-labeled astrocytes, which are commonly used to define the border of the spinal parenchyma after injury, are generally confined to areas around biomaterials rather than migrating into the channels. These astrocytes are considered to be beneficial by limiting secondary injury and possibly facilitating axonal growth (Anderson et al., 2016). Although implants provide for the structural continuity across the lesion, a “gap” composed of invading cells and small cysts frequently exists between hydrogels and the rostral and caudal astrocytic edges/host parenchyma. In vitro studies using alginate hydrogels have shown that growth of fetal CNS axons into alginate channels is always accompanied by astrocytes, suggesting that glia might be required for axon elongation (Pawar et al., 2015). Incorporation of suitable astrocyte subtypes into channels that can mingle and interact with host astrocytes may therefore help to bridge this “gap” and further improve axonal growth into and out of the channels. Studies investigating this hypothesis are ongoing. Conclusions: Taken together, anisotropic biomaterials composed of channels for axon orientation and guidance provide several advantages compared to isotropic biomaterials or transplantation of cell suspensions. Additional approaches such as a combination with cells and transient neurotrophin delivery can improve anatomical and behavioral effects (Figure 1). Further modifications of biomaterials by electrostatic or covalent coating with bioactive molecules and alterations of the stiffness of biomaterials in particular at the host/graft interface might lead to even better tissue integration, may enhance and accelerate vascularization and cell migration, and provide the support necessary for axons to bridge across larger lesions. Supported by grants from the Deutsche Forschungsgemeinschaft (BL414/3-1), International Foundation for Research in Paraplegia, the Indiana University Health – Indiana University School of Medicine Strategic Research Initiative, Indiana Spinal Cord and Brain Injury Research Fund and Morton Cure Paralysis Fund to AB and a Heinz Götze Memorial Fellowship to SL.

  PublisherDOI

• Targeted tissue engineering: hydrogels with linear capillary channels for axonal regeneration after spinal cord injury

  IUScholarWorks (Indiana University) · 2018-04-01

  articleOpen accessSenior author

  Spinal cord injury (SCI) frequently results in the permanent loss of function below the level of injury due to the failure of axonal regeneration in the adult mammalian central nervous system (CNS). The limited intrinsic growth capacity of adult neurons, a lack of growth-promoting factors and the multifactorial inhibitory microenvironment around the lesion site contribute to the lack of axonal regeneration. Strategies such as transplantation of cells, delivery of bioactive compounds and gene transfer have been investigated as a means to promote axonal regrowth through the lesion, to form new synaptic connections and to improve functional outcomes. Although growth of some axonal populations can be robustly enhanced by cellular implants alone or in combination with neurotrophic factors, axons usually extend in random orientation and even reverse growth direction in the lesion site (Figure 1A) (Gros et al., 2010; Günther et al., 2015). Thus, regenerating axons often fail to approach the distal edge of the lesion site, a pre-requisite for proper contact with spared host neurons. The lack of a 3-dimensional organization in the injury site is therefore an additional barrier for successful axonal bridging. Two approaches, physical guidance through structured scaffolds and chemical guidance by growth factor gradients, have emerged as potential means to provide directional cues for axonal growth through the lesion.

  PublisherOA PDF

Recent grants

• Sensorimotor training and cortical mechanisms of pain after spinal cord injury

  NIH · 2018–2022

• NIH Grant R01NS054883

  NIH · $920k · 2011

• Sensorimotor training and cortical mechanisms of pain after spinal cord injury

  NIH · $1 · 2018–2018

• NIH Grant R21NS046466

  NIH · $352k · 2006

Frequent coauthors

• Norbert Weidner

  156 shared

• Mark H. Tuszynski

  University of California, San Diego

  107 shared

• Shengwen Liu

  Chinese Academy of Medical Sciences & Peking Union Medical College

  92 shared

• Beatrice Sandner

  University Hospital Heidelberg

  85 shared

• Radhika Puttagunta

  60 shared

• Paul Lu

  University of California, San Diego

  51 shared

• Timo A. Nees

  35 shared

• M. Brada

  34 shared

Education

• PhD

  Julius-Maximilians-Universität Würzburg

  1995