Allogeneic B cell immunomodulatory therapy in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease. Immune system dysregulation plays an essential role in ALS onset and progression. Our preclinical studies have shown that the administration of exogenous allogeneic B cells improves outcomes in murine models of skin and brain injury through a process termed pligodraxis, in which B cells adopt an immunoregulatory and neuroprotective phenotype in an injured environment.

Intruders or protectors - the multifaceted role of B cells in CNS disorders.

B lymphocytes are immune cells studied predominantly in the context of peripheral humoral immune responses against pathogens. Evidence has been accumulating in recent years on the diversity of immunomodulatory functions that B cells undertake, with particular relevance for pathologies of the central nervous system (CNS). This review summarizes current knowledge on B cell populations, localization, infiltration mechanisms, and function in the CNS and associated tissues.

B cell treatment promotes a neuroprotective microenvironment after traumatic brain injury through reciprocal immunomodulation with infiltrating peripheral myeloid cells.

Traumatic brain injury (TBI) remains a major cause of death and severe disability worldwide. We found previously that treatment with exogenous naïve B cells was associated with structural and functional neuroprotection after TBI. Here, we used a mouse model of unilateral controlled cortical contusion TBI to investigate cellular mechanisms of immunomodulation associated with intraparenchymal delivery of mature naïve B lymphocytes at the time of injury.

Proteomic characterization of spontaneously regrowing spinal cord following injury in the teleost fish Apteronotus leptorhynchus, a regeneration-competent vertebrate.

In adult mammals, spontaneous repair after spinal cord injury (SCI) is severely limited. By contrast, teleost fish successfully regenerate injured axons and produce new neurons from adult neural stem cells after SCI. The molecular mechanisms underlying this high regenerative capacity are largely unknown.

B cells support the repair of injured tissues by adopting MyD88-dependent regulatory functions and phenotype.

Exogenously applied mature naïve B220 /CD19 /IgM /IgD B cells are strongly protective in the context of tissue injury. However, the mechanisms by which B cells detect tissue injury and aid repair remain elusive. Here, we show in distinct models of skin and brain injury that MyD88-dependent toll-like receptor (TLR) signaling through TLR2/6 and TLR4 is essential for the protective benefit of B cells in vivo, while B cell-specific deletion of MyD88 abrogated this effect.

Function of Cathepsin K in the Central Nervous System of Male Mice is Independent of Its Role in the Thyroid Gland.

Cathepsin K deficiency in male mice (Ctsk) results in decreased numbers of hippocampal astrocytes and altered neuronal patterning as well as learning and memory deficits. Additionally, cathepsin K carries essential roles in the thyroid gland where it contributes to the liberation of thyroid hormones (TH). Because TH are essential for brain development, in particular for the cerebellum, we investigated whether cathepsin K's function in the thyroid is directly linked to the brain phenotype of Ctsk mice.

Intraparenchymal Application of Mature B Lymphocytes Improves Structural and Functional Outcome after Contusion Traumatic Brain Injury.

Cerebral contusion causes neurological dysfunction mediated in part by inflammatory responses to injury. B lymphocytes are dynamic regulators of the immune system that have not been systematically studied in traumatic brain injury (TBI). We showed previously that topically applied mature B cells have immunomodulatory properties and strongly promote tissue regeneration, including cutaneous nerve growth, in acute and chronic skin wounds.

Alginate-microencapsulation of human stem cell-derived β cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression.

Pancreatic β-cell replacement by islet transplantation for the treatment of type 1 diabetes (T1D) is currently limited by donor tissue scarcity and the requirement for lifelong immunosuppression. The advent of in vitro differentiation protocols for generating functional β-like cells from human pluripotent stem cells, also referred to as SC-β cells, could eliminate these obstacles. To avoid the need for immunosuppression, alginate-microencapsulation is widely investigated as a safe path to β-cell replacement.

Mature B cells accelerate wound healing after acute and chronic diabetic skin lesions.

Chronic wounds affect 12-15% of patients with diabetes and are associated with a drastic decrease in their quality of life. Here, we demonstrate that purified mature naive B220 /CD19 /IgM /IgD B cells improve healing of acute and diabetic murine wounds after a single topical application. B cell treatment significantly accelerated acute wound closure by 2-3 days in wild-type mice and 5-6 days in obese diabetic mice.

Near-Infrared 1064 nm Laser Modulates Migratory Dendritic Cells To Augment the Immune Response to Intradermal Influenza Vaccine.

Brief exposure of skin to near-infrared (NIR) laser light has been shown to augment the immune response to intradermal vaccination and thus act as an immunologic adjuvant. Although evidence indicates that the NIR laser adjuvant has the capacity to activate innate subsets including dendritic cells (DCs) in skin as conventional adjuvants do, the precise immunological mechanism by which the NIR laser adjuvant acts is largely unknown. In this study we sought to identify the cellular target of the NIR laser adjuvant by using an established mouse model of intradermal influenza vaccination and examining the alteration of responses resulting from genetic ablation of specific DC populations.

Additive neurogenesis supported by multiple stem cell populations mediates adult spinal cord development: A spatiotemporal statistical mapping analysis in a teleost model of indeterminate growth.

The knifefish Apteronotus leptorhynchus exhibits indeterminate growth throughout adulthood. This phenomenon extends to the spinal cord, presumably through the continuous addition of new neurons and glial cells. However, little is known about the developmental dynamics of cells added during adult growth.

Absence of gliosis in a teleost model of spinal cord regeneration.

Among the cellular processes that follow injury to the central nervous system, glial scar formation is thought to be one of the major factors that prevent regeneration. In regeneration-competent organisms, glial scar formation has been a matter of controversy. We addressed this issue by examining the glial population after spinal cord injury in a model of regeneration competency, the knifefish Apteronotus leptorhynchus.

The central nervous system transcriptome of the weakly electric brown ghost knifefish (Apteronotus leptorhynchus): de novo assembly, annotation, and proteomics validation.

Background: The brown ghost knifefish (Apteronotus leptorhynchus) is a weakly electric teleost fish of particular interest as a versatile model system for a variety of research areas in neuroscience and biology. The comprehensive information available on the neurophysiology and neuroanatomy of this organism has enabled significant advances in such areas as the study of the neural basis of behavior, the development of adult-born neurons in the central nervous system and their involvement in the regeneration of nervous tissue, as well as brain aging and senescence. Despite substantial scientific interest in this species, no genomic resources are currently available.

Matrix metalloproteinase-2 and -9 in the cerebellum of teleost fish: Functional implications for adult neurogenesis.

Matrix metalloproteinases (MMPs) are a family of highly conserved zinc-dependent proteases involved in both development and pathogenesis. The present study examines the role of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in adult neurogenesis, using the corpus cerebelli, a subdivision of the cerebellum, of knifefish (Apteronotus leptorhynchus) as a model system. Transcripts of five isoforms of these gelatinases were identified in the central nervous system of this species.

Cell replacement therapy: lessons from teleost fish.

Many disorders of the CNS are characterized by a massive loss of neurons. A promising therapeutic strategy to cure such conditions is based on the activation of endogenous stem cells. Implementation of this strategy will benefit from a better understanding of stem cell dynamics and the local CNS microenvironment in regeneration-competent vertebrate model systems.

Adult stem cells in the knifefish cerebellum.

Adult neurogenesis has been described in dozens of brain regions in teleost fish, with the largest number of new neurons being generated in the cerebellum. Here, we characterized the cerebellar neural stem/progenitor cells (NSPCs) in the brown ghost knifefish (Apteronotus leptorhynchus), an established model system of adult neurogenesis. The majority of the new cerebellar cells arise from neurogenic niches located medially, at the interface of the dorsal/ventral molecular layers and the granular layer.

Quantitative analysis reveals dominance of gliogenesis over neurogenesis in an adult brainstem oscillator.

Neural stem/progenitor cells in the neurogenic niches of the adult brain are widely assumed to give rise predominantly to neurons, rather than glia. Here, we performed a quantitative analysis of the resident neural progenitors and their progeny in the adult pacemaker nucleus (Pn) of the weakly electric fish Apteronotus leptorhynchus. Approximately 15% of all cells in this brainstem nucleus are radial glia-like neural stem/progenitor cells.

Large-scale identification of proteins involved in the development of a sexually dimorphic behavior.

Sexually dimorphic behaviors develop under the influence of sex steroids, which induce reversible changes in the underlying neural network of the brain. However, little is known about the proteins that mediate these activational effects of sex steroids. Here, we used a proteomics approach for large-scale identification of proteins involved in the development of a sexually dimorphic behavior, the electric organ discharge of brown ghost knifefish, Apteronotus leptorhynchus.

Age-related changes in stem cell dynamics, neurogenesis, apoptosis, and gliosis in the adult brain: a novel teleost fish model of negligible senescence.

Adult neurogenesis, the generation of new neurons in the adult central nervous system, is a reported feature of all examined vertebrate species. However, a dramatic decline in the rates of cell proliferation and neuronal differentiation occurs in mammals, typically starting near the onset of sexual maturation. In the present study, we examined possible age-related changes associated with adult neurogenesis in the brain of brown ghost knifefish (Apteronotus leptorhynchus), a teleost fish distinguished by its enormous neurogenic potential.