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Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Neural Regeneration Research 2025年第2期20卷 343-353页

作者： ana Milena Silva Olaya Fernanda Martins Almeida ana maria blanco martinez Suelen Adriani Marques PhD Program in Pathological anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical ***,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord *** of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional *** the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in *** article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were ***,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury stem cell therapy

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Tubular conduits,cell-based therapy and exercise to improve peripheral nerve regeneration

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Neural Regeneration Research 2015年第4期10卷 565-567页

作者： Camila Oliveira Goulart ana maria blanco martinez Laboratório de Neurodegeneracao e Reparo Departamento de PatologiaFaculdade de MedicinaHUCFF-UFRJ-Rio de Janeiro-RJBrazil

Peripheral nerve injuries （PNI） are a major clinical prob- lem. In general, PNI results from motor vehicle accidents, lacerations with sharp objects, penetrating trauma （gunshot wounds） and stretching or crushing trauma and fractures. It is estimated that PNI occur in 2.8% of trauma patients and this number reaches 5% if plexus and root lesions are in- cluded. However, due to lack of recent epidemiological stud- ies, these data probably underestimate the actual number of nerve injuries

关键词： cell Tubular conduits,cell-based therapy and exercise to improve peripheral nerve regeneration PNI

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Absence of galectin-3 attenuates neuroinflammation improving functional recovery after spinal cord injury

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Neural Regeneration Research 2016年第1期11卷 92-93页

作者： Caio Andrade Prins Fernanda Martins Almeida ana maria blanco martinez Laboratorio de Neurodegeneracao e Reparo-Departamento de Patologia-Faculdade de Medicina-HUCFF-UFRJ-Rio de Janeiro-RJ Brazil Instituto de Ciencia Biomedicas UFRJRio de JaneiroRJBrazil

After spinal cord injury （SCI）, a cascade of events begins. At first, there is physical damage with disruption of the blood-brain barrier （BBB） and the integrity of the nervous tissue. The disruption of central ner- vous system （CNS） BBB alters the endothelial permeability, the protein and chemokines expression and the propensity to release in situ inflam- matory cytokines, overcoming anti-inflammatory signals, facilitating the attraction and entry of immune system cells into the injured spinal cord parenchyma （Gaudet et al., 2011）. As a result, there is a neuroin- flammatory response with changes in blood flow, edema, cell infiltra- tion, apoptosis and release of axonal growth inhibitory factors. Nerve function loss occurs when the nerve impulse propagation is interrupted and do not reach its target. This disorder encompasses neuron and glia apoptosis, accompanied by Wallerian degeneration of disconnected axons, and CNS cells exposure to a hostile microenvironment that hampers axon regeneration （Mautes et al., 2000; Harkey et al., 2003）.

关键词： galectin disruption permeability facilitating attraction cascade macrophages cytokines morphologic exposure

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Neuroinflammation and oxidative stress act in concert to promote neurodegeneration in the diabetic retina and optic nerve:galectin-3 participation

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Neural Regeneration Research 2020年第4期15卷 625-635页

作者： Henrique Rocha Mendonca Raul Carpi-Santos Karin da Costa Calaza ana maria blanco martinez Laboratorio de Neurodegeneracao e Reparo Departamento de PatologiaPrograma de Pos-graduacao em Anatomia PatologicaFaculdade de MedicinaHospital Universitrio Clementino Fraga FilhoFederal University of Rio de JaneiroRio de JaneiroBrazil Polo Universitario Macae Unidade Integrada de Pesquisa em Produtos Bioativos e BiocienciasFederal University of Rio de JaneiroMacaeBrazil Laboratorio Integrado de Morfologia Instituto de Biodiversidade e SustentabilidadeNucleo de Pesquisas Ecologicas de MacaeFederal University of Rio de JaneiroMacaeBrazil Laboratorio de Neurobiologia Celular Instituto de Ciencias BiomedicasCentro de Ciencias da SaudeFederal University of Rio de JaneiroRio de JaneiroBrazil Laboratorio de Neurobiologia da Retina Departamento de NeurobiologiaPrograma de Pos-Graduacao em NeurocienciasFluminense Federal UniversityNiteroiBrazil

Diabetes is a lifelong disease characterized by glucose metabolic imbalance,in which low insulin levels or impaired insulin signaling lead to hyperglycemic *** 20 years of diabetes progression,95%of patients will have diabetic retinopathy,the leading cause of visual defects in working-age people *** diabetes is considered a microvascular disease,recent studies have shown that neurodegeneration precedes vascular changes within the diabetic visual system,albeit its mechanisms are still under *** and oxidative stress are intrinsically related phenomena,since macrophage/microglia and astrocytes are the main sources of reactive oxygen species during central nervous system chronic degenerative diseases,and both pathological processes are increased in the visual system during *** present review will focus on recent findings of the contribution of oxidative stress derived from neuroinflammation in the early neurodegenerative aspects of the diabetic visual system and their relationship with galectin-3.

关键词： diabetes diabetic retinopathy galectin-3 neurodegeneration neuroinflammation optic nerve oxidative stress retina

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Inosine: a novel treatment for sciatic nerve injury

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Neural Regeneration Research 2021年第1期16卷 127-128页

作者： Fellipe Soares dos Santos Cardoso ana maria blanco martinez Fernanda Martins de Almeida Laboratório de Neurodegeneração e Reparo–Departamento de anatomia Patológica–Hospital Universitário Clementino Fraga Filho HUCFF/Universidade Federal do Rio de Janeiro Rio de JaneiroBrazil Instituto de Ciências Biomédicas–ICB/Universidade Federal do Rio de Janeiro Rio de JaneiroBrazil

Trauma to the peripheral nervous system often results in loss of motor and sensory functions of the affected area of the body,leading to a series of functional impairments(Allodi et al.,2012).Injuries to peripheral nerves initiate a series of complex events,known as Wallerian degeneration,which allows the injured axons to regenerate and reinnervate their targets(Allodi et al.,2012).Damage to a nerve induces multiple alterations,which include:axonal degeneration,breakdown of myelin sheath,Schwann cells(SC)proliferation and conversion to a repair phenotype which express cytokines and chemokines that allow the infiltration and activation of macrophages(Mietto et al.,2015;Jessen and Mirsky,2016).

关键词： al. degeneration alterations

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Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice

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Neural Regeneration Research 2018年第6期13卷 1046-1053页

作者： Bruna dos Santos Ramalho FernANDa Martins de Almeida Conrado Mendonca Sales Silmara de Lima ana maria blanco martinez Laboratorio de Neurodegeneracao e Reparo Departamento de Patologia - Faculdade de Medicina HUCFF Universidade Federal do Rio de Janeiro Rio de laneiro Brazil

In spite of advances in surgical care and rehabilitation, the consequences of spinal cord injury （SCI） are still challenging. Several experimental therapeutic strategies have been studied in the SCI field, and recent advances have led to the development of therapies that may act on the inhibitory microenvironment. Assorted lineages of stem cells are considered a good treatment for SCI. This study investigated the effect of systemic transplantation of mesenchymal stem cells （MSCs） in a compressive SCI model. Here we present results of the intraperitoneal route, which has not been used previously for MSC administration after compressive SCI. We used adult female C57BL/6 mice that underwent laminectomy at the T9 level, followed by spinal cord compression for 1 minute with a 30-g vascular clip. The animals were divided into five groups： sham （anesthesia and laminectomy but without compression injury induction）, MSC i.p. （intraperitoneal injection of 8×10^5 MSCs in 500 μL of DMEM at 7 days after SCI）, MSC i.v. （intravenous injection of 8 × 10^5 MSCs in 500μL of DMEM at 7 days after SCI）, DMEM i.p. （intraperitoneal injection of 500μL of DMEM at 7 days after SCI）, DMEM i.v. （intravenous injection of 500 μL of DMEM at 7 days after SCI）. The effects of MSCs transplantation in white matter sparing were analyzed by luxol fast blue staining. The number of preserved fibers was counted in semithin sections stained with toluidine blue and the presence of trophic factors was analyzed by immunohistochemistry. In addition, we analyzed the locomotor performance with Basso Mouse Scale and Global Mobility Test. Our results showed white matter preservation and a larger number of preserved fibers in the MSC groups than in the DMEM groups. Furthermore, the MSC groups had higher levels of trophic factors （brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and neurotrophin-4） in the spinal cord and improved locomotor performance. Our results indicate that injection of MSC

关键词： spinal cord injury mesenchymal stem cells intravenous route intraperitoneal route functional recovery systemic transplantation neural regeneration

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Molecular approaches for spinal cord injury treatment

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Neural Regeneration Research 2023年第1期18卷 23-30页

作者： Fernanda Martins de Almeida Suelen Adriani Marques Anne Caroline Rodrigues dos Santos Caio Andrade Prins Fellipe Soares dos Santos Cardoso Luiza dos Santos Heringer Henrique Rocha Mendonça ana maria blanco martinez Laboratório de Neurodegeneração e Reparo Programa de Pós-Graduação em Medicina:Anatomia PatológicaDepartamento de PatologiaFaculdade de MedicinaHospital Universitário Clementino Fraga FilhoCentro de Ciências da SaúdeUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil Instituto de Ciências Biomédicas Centro de Ciências da SaúdeUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil Instituto de Biologia Departamento de NeurobiologiaLaboratório de Regeneração Neural e FunçãoUFFRio de JaneiroBrazil Laboratório Integrado de Morfologia Instituto de Biodiversidade e Sustentabilidade NUPEMPrograma de Pós-graduação Multicêntrico em Ciências Fisiológicas-SBFisCentro Multidisciplinar UFRJ-MacaéUniversidade Federal do Rio de JaneiroMacaéBrazil

Injuries to the spinal cord result in permanent disabilities that limit daily life *** main reasons for these poor outcomes are the limited regenerative capacity of central neurons and the inhibitory milieu that is established upon traumatic *** decades of research,there is still no efficient treatment for spinal cord *** strategies are tested in preclinical studies that focus on ameliorating the functional outcomes after spinal cord *** these,molecular compounds are currently being used for neurological recovery,with promising *** molecules target the axon collapsed growth cone,the inhibitory microenvironment,the survival of neurons and glial cells,and the re-establishment of lost *** this review we focused on molecules that are being used,either in preclinical or clinical studies,to treat spinal cord injuries,such as drugs,growth and neurotrophic factors,enzymes,and *** mechanisms of action of these molecules are discussed,considering traumatic spinal cord injury in rodents and humans.

关键词： axonal regeneration drugs enzymes growth factors molecular therapy neurotrophic factors purines spinal cord injury

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Comparison of morphological and functional outcomes of mouse sciatic nerve repair with three biodegradable polymer conduits containing poly (lactic acid)

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Neural Regeneration Research 2018年第10期13卷 1811-1819页

作者： Fernanda Marques Pestana Rui C.C.Domingues Júlia Teixeira Oliveira Daniela F.P.A.Durco Camila Oliveira Goulart Henrique Rocha Mendonca Anne Caroline Rodrigues dos Santos Natália Tavares de Campos Beatriz Theodoro da Silva Cristina Cardoso Pereira Cristiano Piacsek Borges ana maria blanco martinez Pós Graduacao em Ciências Morfológicas Instituto de Ciências Biomédicas-UFRJRio de Janeiro RJ Brazil anatomia Patológica-Faculdade de Medicina-HUCFF-UFRJ Rio de Janeiro RJ Brazil Laboratório de Neurodegeneracao e Reparo-Faculdade de Medicina-HUCFF-UFRJ Rio de Janeiro RJ Brazil Programa de Eng. Química COPPE-UFRJRio de Janeiro Brazil Polo Universitário de Macaé Laboratório Integrado de Produtos Bioativos e BiociênciasMacaê UFRJ Brazil

Poly（lactic acid）（PLA）-containing nerve guidance conduits（NGCs） are currently being investigated for nerve repair as an alternative to autograft, which leads to permanent functional impairment in the territory innervated by the removed nerve. Combination of polymers modifies the physical properties of the conduits, altering their nerve-guidance properties. Conduits made from PLA-only or combined with other polymers have been used successfully for nerve repair, but their efficiency has not been compared. We compared the morphological and functional outcomes of peripheral nerve repair by using NGCs made of poly（lactic acid） and combined or not with polycaprolactone（PLA/PCL） or polyvinylpyrrolidone（PLA/PVP）. To assess the functional recovery, we employed a mechanical hyperalgesia analysis, sciatic functional index（SFI）, and electroneuromyography. The mechanical hyperalgesia analysis showed that the PLA group improved more rapidly than the PLA/PVP and PLA/PCL groups; similarly, in the electroneuromyography assay, the PLA group exhibited higher amplitude than the PLA/PCL and PLA/PVP groups. However, the SFI improvement rates did not differ among the groups. Morphologically, the PLA group showed more vascularization, while the nerve fiber regeneration did not differ among the groups. In conclusion, the PLA-only conduits were superior to the other NGCs tested for nerve repair.

关键词： sciatic nerve tubulization biodegradable conduit poly(lactic acid) regeneration

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WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Neurotrauma and mesenchymal stem cells treatment:From experimental studies to clinical trials

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World Journal of Stem Cells 2014年第2期6卷 179-194页

作者： ana maria blanco martinez Camila de Oliveira Goulart Bruna dos Santos Ramalho Júlia Teixeira Oliveira Fernanda Martins Almeida Laboratory of Neurodegeneration and Repair Institute of Biomedical SciencesHealth Science Center Pathology Department Faculty of MedicineFederal University of Rio de Janeiro Federal University of Rio de Janeiro Campus Macaé

Mesenchymal stem cell(MSC)therapy has attracted the attention of scientists and clinicians around the *** and pre-clinical experimental studies have highlighted the positive effects of MSC treatment after spinal cord and peripheral nerve *** effects are believed to be due to their ability to differentiate into other cell lineages,modulate inflammatory and immunomodulatory responses,reduce cell apoptosis,secrete several neurotrophic factors and respond to tissue injury,among *** are many pre-clinical studies on MSC treatment for spinal cord injury(SCI)and peripheral nerve ***,the same is not true for clinical trials,particularly those concerned with nerve trauma,indicating the necessity of more well-constructed studies showing the benefits that cell therapy can provide for individuals suffering the consequences of nerve *** for clinical trials for SCI treatment the results obtained so far are not as beneficial as those described in experimental *** these reasons basic and pre-clinical studies dealing with MSC therapy should emphasize the standardization of protocols that could be translated to the clinical set with consistent and positive *** review is based on pre-clinical studies and clinical trials available in the literature from 2010 until *** the time of writing this article there were 43 and 36 pre-clinical and 19 and 1 clinical trials on injured spinal cord and peripheral nerves,respectively.

关键词： Neurotrauma Stem cell therapy Mesenchymal stem cells Pre-clinical studies Clinical trials

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Challenges and improvement strategies in the hospitalization of chronic multimorbid patients

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World Journal of Clinical Cases 2025年第3期13卷 35-41页

作者： Andres Fontalba-Navas Francisco Pozo Muñoz Rogelio Garcia Cisneros maria Jose Garcia Larrosa maria del Mar Callejon Gil Ignacio Garcia Delgado maria Belen Jimenez martinez Antequera Hospital Northern Málaga Integrated Healthcare AreaAntequera 29200AndalusiaSpain Department of Public Health and Psychiatry University of MálagaMálaga 29010Spain Antequera Hospital Northern Málaga Antequera Integrated Healthcare AreaAntequera 29200MálagaSpain

BACKGROUND Addressing the growing challenge of hospitalizing chronic multimorbid patients,this study examines the strain these conditions impose on healthcare systems at a local level,focusing on a pilot *** diseases and complex patients require comprehensive management strategies to reduce healthcare burdens and improve patient *** proven effective,this pilot model has the potential to be replicated in other healthcare settings to enhance the management of chronic multimorbid *** To evaluate the effectiveness of the high complexity unit(HCU)in managing chronic multimorbid patients through a multidisciplinary care model and to compare it with standard hospital *** The study employed a descriptive longitudinal approach,analyzing data from the Basic Minimum Data Set(BMDS)to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout *** HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity *** The study employed a descriptive longitudinal approach,analyzing data from the BMDS to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout *** HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity *** This study demonstrates the effectiveness of the HCU in managing patients with complex chronic diseases through a multidisciplinary *** coordinated care provided by the HCU results in improved patient outcomes,reduced unnecessary hospitalizations,and better management of patient *** superiority of the HCU compared to standard care is evident in key outcomes such as fewer readmissions and higher patient satisfaction,reinforcing its value as a model of ca

关键词： High complexity unit Chronic multimorbidity Patient-centered care Integrated care Healthcare management

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