Long chain capsaicin analogues synthetized by CALB-CLEAs show cytotoxicity on glioblastoma cell lines.

Glioblastoma is one of the most lethal tumors, displaying striking cellular heterogeneity and drug resistance. The prognosis of patients suffering from glioblastoma after 5 years is only 5%. In the present work, capsaicin analogues bearing modifications on the acyl chain with long-chain fatty acids showed promising anti-tumoral activity by its cytotoxicity on U-87 and U-138 glioblastoma multiforme cells. The capsaicin analogues were enzymatically synthetized with cross-linked enzyme aggregates of lipase B from Candida antarctica (CALB). The catalytic performance of recombinant CALB-CLEAs was compared to their immobilized form on a hydrophobic support. After 72 h of reaction, the synthesis of capsaicin analogues from linoleic acid, docosahexaenoic acid, and punicic acid achieved a maximum conversion of 69.7, 8.3 and 30.3% with CALB-CLEAs, respectively. Similar values were obtained with commercial CALB, with conversion yields of 58.3, 24.2 and 22% for capsaicin analogues from linoleic acid, DHA and punicic acid, respectively. Olvanil and dohevanil had a significant cytotoxic effect on both U-87 and U-138 glioblastoma cells. Irrespective of the immobilization form, CALB is an efficient biocatalyst for the synthesis of anti-tumoral capsaicin derivatives. KEY POINTS: • This is the first report concerning the enzymatic synthesis of capsaicin analogues from docosahexaenoic acid and punicic acid with CALB-CLEAs. • The viability U-87 and U-138 glioblastoma cells was significantly affected after incubation with olvanil and dohevanil. • Capsaicin analogues from fatty acids obtained by CALB-CLEAs are promising candidates for therapeutic use as cytotoxic agents in glioblastoma cancer cells.

Chitosan-Hydroxycinnamic Acids Conjugates: Emerging Biomaterials with Rising Applications in Biomedicine.

Over the past thirty years, research has shown the huge potential of chitosan in biomedical applications such as drug delivery, tissue engineering and regeneration, cancer therapy, and antimicrobial treatments, among others. One of the major advantages of this interesting polysaccharide is its modifiability, which facilitates its use in tailor-made applications. In this way, the molecular structure of chitosan has been conjugated with multiple molecules to modify its mechanical, biological, or chemical properties. Here, we review the conjugation of chitosan with some bioactive molecules: hydroxycinnamic acids (HCAs); since these derivatives have been probed to enhance some of the biological effects of chitosan and to fine-tune its characteristics for its application in the biomedical field. First, the main characteristics of chitosan and HCAs are presented; then, the currently employed conjugation strategies between chitosan and HCAs are described; and, finally, the studied biomedical applications of these derivatives are discussed to present their limitations and advantages, which could lead to proximal therapeutic uses.

Intranasal Administration of Undifferentiated Oligodendrocyte Lineage Cells as a Potential Approach to Deliver Oligodendrocyte Precursor Cells into Brain.

Oligodendrocyte precursor cell (OPC) migration is a mechanism involved in remyelination; these cells migrate from niches in the adult CNS. However, age and disease reduce the pool of OPCs; as a result, the remyelination capacity of the CNS decreases over time. Several experimental studies have introduced OPCs to the brain via direct injection or intrathecal administration. In this study, we used the nose-to brain pathway to deliver oligodendrocyte lineage cells (human oligodendroglioma (HOG) cells), which behave similarly to OPCs in vitro. To this end, we administered GFP-labelled HOG cells intranasally to experimental animals, which were subsequently euthanised at 30 or 60 days. Our results show that the intranasal route is a viable route to the CNS and that HOG cells administered intranasally migrate preferentially to niches of OPCs (clusters created during embryonic development and adult life). Our study provides evidence, albeit limited, that HOG cells either form clusters or adhere to clusters of OPCs in the brains of experimental animals.

Recombinant Erythropoietin Provides Protection against Renal Fibrosis in Adenine-Induced Chronic Kidney Disease.

Chronic kidney disease (CKD) causes anemia by renal damage. In CKD, the kidney is submitted to hypoxia, persistent inflammation, leading to fibrosis and permanent loss of renal function. Human recombinant erythropoietin (rEPO) has been widely used to treat CKD-associated anemia and is known to possess organ-protective properties that are independent from its well-established hematopoietic effects. Nonhematopoietic effects of EPO are mediated by an alternative receptor that is proposed to consist of a heterocomplex between the erythropoietin receptor (EPOR) and the beta common receptor (ßcR). The present study explored the effects of rEPO to prevent renal fibrosis in adenine-induced chronic kidney disease (Ad-CKD) and their association with the expression of the heterodimer EPOR/ßcR. Male Wistar rats were randomized to control group (CTL), adenine-fed rats (Ad-CKD), and Ad-CKD with treatment of rEPO (1050 IU/kg, once weekly for 4 weeks). Ad-CKD rats exhibited anemia, uremia, decreased renal function, increased infiltration of inflammatory cells, tubular atrophy, and fibrosis. rEPO treatment not only corrected anemia but reduced uremia and partially improved renal function as well. In addition, we observed that rEPO diminishes tubular injury, prevents fibrosis deposition, and induces the EPOR/ßcR heteroreceptor. The findings may explain the extrahematopoietic effects of rEPO in CKD and provide new strategies for the treatment of renal fibrosis in CKD.

Docosahexaenoic Acid (DHA), Vitamin D3, and Probiotics Supplementation Improve Memory, Glial Reactivity, and Oxidative Stress Biomarkers in an Aluminum-Induced Cognitive Impairment Rat Model.

Globally, the rise in neurodegenerative issues in tandem with shifts in lifestyle and aging population has prompted a search for effective interventions. Nutraceutical compounds have emerged as promising agents for addressing these challenges. This 60-day study on an aluminum-induced cognitive impairment rat model assessed three compounds and their combinations: probiotics (Prob, Lactobacillus plantarum [5 × 1010 CFU/day], and Lactobacillus acidophilus [5 × 1010 CFU/day]), docosahexaenoic acid (DHA, 23.8 mg/day), and vitamin D3 (VD3, 150 IU/day). Behavioral outcomes were evaluated by using the Morris water maze and novel object recognition tests. Glial activation was assessed through immunofluorescence analysis of GFAP/Iba1, and oxidative stress markers in brain tissue were determined by measuring the levels of Malondialdehyde (MDA) and Superoxide dismutase (SOD). The results demonstrated a progressive improvement in the learning and memory capacity. The aluminum group exhibited the poorest performance in the behavioral test, enhanced GFAP/Iba1 activation, and elevated levels of oxidative stress markers. Conversely, the DHA + Prob + VD3 treatment demonstrated the best performance in the Morris water maze. The combination of DHA + Prob + VD3 exhibited superior performance in the Morris water maze, accompanied by reduced levels of GFAP/Iba1 activation in DG/CA1 brain regions. Furthermore, DHA + Prob supplementation showed lower GFAP/Iba1 activation in the CA3 region and enhanced antioxidant activity. In summary, supplementing various nutraceutical combinations, including DHA, VD3, and Prob, displayed notable benefits against aluminum-induced cognitive impairment. These benefits encompassed memory enhancement, diminished MDA concentration, increased SOD activity, and reduced glial activation, as indicated by GFAP/Iba1 markers.

In Vitro Antiviral Activity of Nordihydroguaiaretic Acid against SARS-CoV-2.

The coronavirus infectious disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has been spreading rapidly worldwide, creating a pandemic. This article describes the evaluation of the antiviral activity of nordihydroguaiaretic acid (NDGA), a molecule found in Creosote bush (Larrea tridentata) leaves, against SARS-CoV-2 in vitro. A 35 µM concentration of NDGA was not toxic to Vero cells and exhibited a remarkable inhibitory effect on the SARS-CoV-2 cytopathic effect, viral plaque formation, RNA replication, and expression of the SARS-CoV-2 spike glycoprotein. The 50% effective concentration for NDGA was as low as 16.97 µM. Our results show that NDGA could be a promising therapeutic candidate against SARS-CoV-2.

Mesenchymal Stem Cell-Based Therapies in the Post-Acute Neurological COVID Syndrome: Current Landscape and Opportunities.

One of the main concerns related to SARS-CoV-2 infection is the symptoms that could be developed by survivors, known as long COVID, a syndrome characterized by persistent symptoms beyond the acute phase of the infection. This syndrome has emerged as a complex and debilitating condition with a diverse range of manifestations affecting multiple organ systems. It is increasingly recognized for affecting the Central Nervous System, in which one of the most prevalent manifestations is cognitive impairment. The search for effective therapeutic interventions has led to growing interest in Mesenchymal Stem Cell (MSC)-based therapies due to their immunomodulatory, anti-inflammatory, and tissue regenerative properties. This review provides a comprehensive analysis of the current understanding and potential applications of MSC-based interventions in the context of post-acute neurological COVID-19 syndrome, exploring the underlying mechanisms by which MSCs exert their effects on neuroinflammation, neuroprotection, and neural tissue repair. Moreover, we discuss the challenges and considerations specific to employing MSC-based therapies, including optimal delivery methods, and functional treatment enhancements.

Curcumin protects against the oxidative damage induced by the pesticide parathion in the hippocampus of the rat brain.

UNLABELLED: One of the main concerns regarding organophosphate pesticides (OP) is their possible toxic effects. Doses that do not produce acute toxicity are capable of altering the structure and biochemistry of different tissues and organs by production of reactive oxygen species (ROS). Curcumin (CUR) is the main substance in Curcuma longa (Zingiberacea) rhizome that has strong antioxidant activity. However, the neuroprotective properties of curcumin against oxidative stress induced by prolonged exposure to parathion (PAR) is not clear. OBJECTIVE: The present work evaluated the protective effect of curcumin against the oxidative damage induced in the rat hippocampus by the OP PAR. METHODS: Forty female Wistar rats were distributed in four groups as follows: exposed to PAR by inhalation (PAR group); pre-treated with CUR and then exposed to PAR by inhalation, (CUR + PAR group); exposed to environmental air and treated with CUR in the food (CUR group); and exposed to environmental air (the control group). At the end of the handling process, the concentration of erythrocyte cholinesterase was monitored, as indicator of PAR intoxication and lipoperoxidation, immunohistochemistry for astrocytes, and activated microglia and apoptosis was determined in the hippocampus. RESULTS: In the present study, we show that the administration of CUR (200 mg/kg body weight) significantly diminished the oxidative damage in the hippocampus of rats exposed to the OP PAR. DISCUSSION: These data suggest that CUR may be an alternative to prevent neurodegenerative damage after pesticide exposure.

PSEN1 c.1292C<A Variant and Early-Onset Alzheimer's Disease: A Scoping Review.

Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive loss of cognitive function, with ß-amyloid plaques and neurofibrillary tangles being its major pathological findings. Although the disease mainly affects the elderly, c. 5-10% of the cases are due to PSEN1, PSEN2, and APP mutations, principally associated with an early onset of the disease. The A413E (rs63750083) PSEN1 variant, identified in 2001, is associated with early-onset Alzheimer's disease (EOAD). Although there is scant knowledge about the disease's clinical manifestations and particular features, significant clinical heterogeneity was reported, with a high incidence of spastic paraparesis (SP), language impairments, and psychiatric and motor manifestations. This scoping review aims to synthesize findings related to the A431E variant of PSEN1. In the search, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the guidelines proposed by Arksey and O'Malley. We searched and identified 247 studies including the A431E variant of PSEN1 from 2001 to 2021 in five databases and one search engine. After the removal of duplicates, and apply inclusion criteria, 42 studies were finally included. We considered a narrative synthesis with a qualitative approach for the analysis of the data. Given the study sample conformation, we divided the results into those carried out only with participants carrying A431E (seven studies), subjects with PSEN variants (11 studies), and variants associated with EOAD in PSEN1, PSEN2, and APP (24 studies). The resulting synthesis indicates most studies involve Mexican and Mexican-American participants in preclinical stages. The articles analyzed included carrier characteristics in categories such as genetics, clinical, imaging techniques, neuropsychology, neuropathology, and biomarkers. Some studies also considered family members' beliefs and caregivers' experiences. Heterogeneity in both the studies found and carrier samples of EOAD-related gene variants does not allow for the generalization of the findings. Future research should focus on reporting data on the progression of carrier characteristics through time and reporting results independently or comparing them across variants.

Effects of Etanercept on TNF-α Inhibition in Rats with Adenine-Induced Chronic Kidney Disease.

Introduction: Chronic kidney disease (CKD) constitutes a chronic inflammatory state associated with an increase in inflammatory mediators and profibrotic molecules such as tumor necrosis factor-α (TNF-α). Etanercept (ETA) is a TNF inhibitor widely used in treatment of autoimmune inflammatory diseases. However, the effects of TNF-α inhibition in the establishment of CKD have not been fully elucidated. We evaluate the effects of TNF inhibition by ETA in adenine- (Ad-) induced CKD in rats. Methods: Rats were divided into three groups: control, renal injury model, and model plus ETA (2 mg/kg, 3 times per week (w); sc). Renal injury was induced by Ad administration (100 mg/kg, daily for 2 or 4 w; orogastric). Serum TNF-α levels and biochemical parameters for renal function were evaluated. Histopathological changes in the kidney were assessed using H&E and Masson's trichrome staining and also immunostaining for tubular cells. Results: Ad administration produced a renal functional decline, tubular atrophy, interstitial inflammation, and fibrosis for 2 w, followed by renal anemia, several renal dysfunctions, tubular atrophy, and fibrosis at 4 w. A significant increase in serum TNF-α levels was observed from 2 w of Ad administration and remained elevated up to 4 w. Treatment with ETA partially reduced kidney damage but was very effective to blocking serum TNF-α. Conclusion: Although inhibition of TNF by ETA was very effective in reducing serum TNF-α, this strategy was partially effective in preventing Ad-induced CKD.

Presenilin mutations and their impact on neuronal differentiation in Alzheimer's disease.

The presenilin genes (PSEN1 and PSEN2) are mainly responsible for causing early-onset familial Alzheimer's disease, harboring ~300 causative mutations, and representing ~90% of all mutations associated with a very aggressive disease form. Presenilin 1 is the catalytic core of the γ-secretase complex that conducts the intramembranous proteolytic excision of multiple transmembrane proteins like the amyloid precursor protein, Notch-1, N- and E-cadherin, LRP, Syndecan, Delta, Jagged, CD44, ErbB4, and Nectin1a. Presenilin 1 plays an essential role in neural progenitor maintenance, neurogenesis, neurite outgrowth, synaptic function, neuronal function, myelination, and plasticity. Therefore, an imbalance caused by mutations in presenilin 1/γ-secretase might cause aberrant signaling, synaptic dysfunction, memory impairment, and increased Aß42/Aß40 ratio, contributing to neurodegeneration during the initial stages of Alzheimer's disease pathogenesis. This review focuses on the neuronal differentiation dysregulation mediated by PSEN1 mutations in Alzheimer's disease. Furthermore, we emphasize the importance of Alzheimer's disease-induced pluripotent stem cells models in analyzing PSEN1 mutations implication over the early stages of the Alzheimer's disease pathogenesis throughout neuronal differentiation impairment.

Potential benefits of structured lipids in bulk compound chocolate: Insights on bioavailability and effect on serum lipids.

The bioavailability impact of serum lipids in compound chocolate products based on structured lipids was studied. Compound chocolate products containing fat with and without structured lipids were digested in vitro under simulated gastrointestinal lipolysis conditions and were studied in vivo in healthy C57BL/6J mice. The in vitro digestion results show that products containing structured lipids, milk compound chocolate filling and white compound coating, significantly reduced the release rate of Free Fatty Acids (FFA) and improved the caloric reduction between 12.49% and 13.71% compared to products without structured lipids, suggesting that FFA were not absorbed. Animal feeding studies revealed no adverse effects on the compound products intake; in fact, these products reduced total cholesterol, LDL-c, VLDL-c and triacylglycerols. The present work shows the relevance of developing functional compound chocolate as providing a potential healthy initiative through the biological effect of the bioactive ingredients incorporated.

Exosomes and Biomaterials: In Search of a New Therapeutic Strategy for Multiple Sclerosis.

Current efforts to find novel treatments that counteract multiple sclerosis (MS) have pointed toward immunomodulation and remyelination. Currently, cell therapy has shown promising potential to achieve this purpose. However, disadvantages such as poor survival, differentiation, and integration into the target tissue have limited its application. A series of recent studies have focused on the cell secretome, showing it to provide the most benefits of cell therapy. Exosomes are a key component of the cell secretome, participating in the transfer of bioactive molecules. These nano-sized vesicles offer many therapeutical advantages, such as the capacity to cross the blood-brain barrier, an enrichable cargo, and a customizable membrane. Moreover, integrating of biomaterials into exosome therapy could lead to new tissue-specific therapeutic strategies. In this work, the use of exosomes and their integration with biomaterials is presented as a novel strategy in the treatment of MS.

Nose-to-Brain: The Next Step for Stem Cell and Biomaterial Therapy in Neurological Disorders.

Neurological disorders are a leading cause of morbidity worldwide, giving rise to a growing need to develop treatments to revert their symptoms. This review highlights the great potential of recent advances in cell therapy for the treatment of neurological disorders. Through the administration of pluripotent or stem cells, this novel therapy may promote neuroprotection, neuroplasticity, and neuroregeneration in lesion areas. The review also addresses the administration of these therapeutic molecules by the intranasal route, a promising, non-conventional route that allows for direct access to the central nervous system without crossing the blood-brain barrier, avoiding potential adverse reactions and enabling the administration of large quantities of therapeutic molecules to the brain. Finally, we focus on the need to use biomaterials, which play an important role as nutrient carriers, scaffolds, and immune modulators in the administration of non-autologous cells. Little research has been conducted into the integration of biomaterials alongside intranasally administered cell therapy, a highly promising approach for the treatment of neurological disorders.

Biocompatibility of ferulic/succinic acid-grafted chitosan hydrogels for implantation after brain injury: A preliminary study.

Nowadays it is known that neural cells are capable of regenerating after brain injury, but their success highly depends on the local environment, including the presence of a biological structure to support cell proliferation and restore the lost tissue. Different chitosan-based biomaterials have been employed in response to this necessity. We hypothesized that hydrogels made of antioxidant compounds functionalizing chitosan could provide a suitable environment to home new cells and offer a way to achieve brain repair. In this work, the implantation of functionalized chitosan biomaterials in a brain injury animal model was evaluated. The injury consisted of mechanical damage applied to the cerebral cortex of Wistar rats followed by the implantation of four different chitosan-based biomaterials. After 15 and 30 days, animals underwent magnetic resonance imaging, then they were sacrificed, and the brain tissue was analyzed by immunohistochemistry. The proliferation of microglia and astrocytes increased at the lesion zone, showing differences between the evaluated biomaterials. Also, cell nuclei were seen inside the biomaterials, indicating cell migration and biodegradation. Chitosan-based hydrogels are able to fill in the tissue cavity and bare cells for the endogenous restoration process. The addition of ferulic and succinic acid to the chitosan structure increases this capacity and decreases the inflammatory reaction to the implant.

A Three-Dimensional Alzheimer's Disease Cell Culture Model Using iPSC-Derived Neurons Carrying A246E Mutation in PSEN1.

Alzheimer's disease (AD) is a chronic brain disorder characterized by progressive intellectual decline and memory and neuronal loss, caused mainly by extracellular deposition of amyloid-ß (Aß) and intracellular accumulation of hyperphosphorylated tau protein, primarily in areas implicated in memory and learning as prefrontal cortex and hippocampus. There are two forms of AD, a late-onset form that affects people over 65 years old, and the early-onset form, which is hereditable and affect people at early ages ~45 years. To date, there is no cure for the disease; consequently, it is essential to develop new tools for the study of processes implicated in the disease. Currently, in vitro AD three-dimensional (3D) models using induced pluripotent stem cells (iPSC)-derived neurons have broadened the horizon for in vitro disease modeling and gained interest for mechanistic studies and preclinical drug discovery due to their potential advantages in providing a better physiologically relevant information and more predictive data for in vivo tests. Therefore, this study aimed to establish a 3D cell culture model of AD in vitro using iPSCs carrying the A246E mutation. We generated human iPSCs from fibroblasts from a patient with AD harboring the A246E mutation in the PSEN1 gene. Cell reprogramming was performed using lentiviral vectors with Yamanaka's factors (OSKM: Oct4, Sox2, Klf4, and c-Myc). The resulting iPSCs expressed pluripotency genes (such as Nanog and Oct4), alkaline phosphatase activity, and pluripotency stem cell marker expression, such as OCT4, SOX2, TRA-1-60, and SSEA4. iPSCs exhibited the ability to differentiate into neuronal lineage in a 3D environment through dual SMAD inhibition as confirmed by Nestin, MAP2, and Tuj1 neural marker expression. These iPSC-derived neurons harbored Aß oligomers confirmed by Western Blot (WB) and immunostaining. With human iPSC-derived neurons able to produce Aß oligomers, we established a novel human hydrogel-based 3D cell culture model that recapitulates Aß aggregation without the need for mutation induction or synthetic Aß exposure. This model will allow the study of processes implicated in disease spread throughout the brain, the screening of molecules or compounds with therapeutic potential, and the development of personalized therapeutic strategies.

Potential of Chitosan and Its Derivatives for Biomedical Applications in the Central Nervous System.

It is well known that the central nervous system (CNS) has a limited regenerative capacity and that many therapeutic molecules cannot cross the blood brain barrier (BBB). The use of biomaterials has emerged as an alternative to overcome these limitations. For many years, biomedical applications of chitosan have been studied due to its remarkable biological properties, biocompatibility, and high versatility. Moreover, the interest in this biomaterial for CNS biomedical implementation has increased because of its ability to cross the BBB, mucoadhesiveness, and hydrogel formation capacity. Several chitosan-based biomaterials have been applied with promising results as drug, cell and gene delivery vehicles. Moreover, their capacity to form porous scaffolds and to bear cells and biomolecules has offered a way to achieve neural regeneration. Therefore, this review aims to bring together recent works that highlight the potential of chitosan and its derivatives as adequate biomaterials for applications directed toward the CNS. First, an overview of chitosan and its derivatives is provided with an emphasis on the properties that favor different applications. Second, a compilation of works that employ chitosan-based biomaterials for drug delivery, gene therapy, tissue engineering, and regenerative medicine in the CNS is presented. Finally, the most interesting trends and future perspectives of chitosan and its derivatives applications in the CNS are shown.

Sex-dependent mechanisms involved in renal tolerance to ischemia-reperfusion: Role of inflammation and histone H3 citrullination.

Ischemia-reperfusion (I/R) injury, an inevitable result of kidney transplantation, triggers early inflammatory events that affect graft viability. Evidence from human transplantation and preclinical models of I/R suggests that a female hormonal environment positively influences the ability to recover from ischemic injury. However, the mechanisms behind these effects remain mostly unexplored. Here, we studied the influence of sex on pro-inflammatory mediators involved in the pathophysiology of acute I/R injury in male, female, and female ovariectomized (OVX) Wistar rats that underwent unilateral renal ischemia for 45 min, followed by 24 h of reperfusion. We found improved renal function, reduced cytokine expression, and decreased infiltration of myeloperoxidase-positive cells in females after I/R, when compared to their male and female OVX counterparts. Remarkably, citrullination of histone H3 was exacerbated in serum and renal tubules of females after I/R. In contrast, we observed lower levels of citrullinated histone H3 in male and female OVX rats in response to I/R, mostly in neutrophil extracellular traps. Our results demonstrate that female sex promotes renal I/R tolerance by attenuating pro-inflammatory mediators involved in I/R-induced damage.

Experimental Models for the Study of Central Nervous System Infection by SARS-CoV-2.

INTRODUCTION: The response to the SARS-CoV-2 coronavirus epidemic requires increased research efforts to expand our knowledge of the disease. Questions related to infection rates and mechanisms, the possibility of reinfection, and potential therapeutic approaches require us not only to use the experimental models previously employed for the SARS-CoV and MERS-CoV coronaviruses but also to generate new models to respond to urgent questions. DEVELOPMENT: We reviewed the different experimental models used in the study of central nervous system (CNS) involvement in COVID-19 both in different cell lines that have enabled identification of the virus' action mechanisms and in animal models (mice, rats, hamsters, ferrets, and primates) inoculated with the virus. Specifically, we reviewed models used to assess the presence and effects of SARS-CoV-2 on the CNS, including neural cell lines, animal models such as mouse hepatitis virus CoV (especially the 59 strain), and the use of brain organoids. CONCLUSION: Given the clear need to increase our understanding of SARS-CoV-2, as well as its potential effects on the CNS, we must endeavor to obtain new information with cellular or animal models, with an appropriate resemblance between models and human patients.

Particles Containing Cells as a Strategy to Promote Remyelination in Patients With Multiple Sclerosis.

The repair of demyelinated lesions is a key objective in multiple sclerosis research. Remyelination fundamentally depends on oligodendrocyte progenitor cells (OPC) reaching the lesion; this is influenced by numerous factors including age, disease progression time, inflammatory activity, and the pool of OPCs available, whether they be NG2 cells or cells derived from neural stem cells. Administering OPCs has been proposed as a potential cell therapy; however, these cells can only be administered directly. This article discusses the potential administration of OPCs encapsulated within hydrogel particles composed of biocompatible biomaterials, via the nose-to-brain pathway. We also discuss conditions for the indication of this therapy, and such related issues as the influence on endogenous remyelination, migration of OPCs to demyelinated areas, and the immune response, given the autoimmune nature of multiple sclerosis. Chitosan and derivatives constitute the most promising biomaterial for this purpose, although these issues must be addressed. In conclusion, this line of research may yield an alternative to the remyelinating drugs currently being studied.