Using iPS Cells toward the Understanding of Parkinson's Disease

Cellular reprogramming of somatic cells to human pluripotent stem cells (iPSC) represents an efficient tool for in vitro modeling of human brain diseases and provides an innovative opportunity in the identification of new therapeutic drugs. Patient-specific iPSC can be differentiated into disease-relevant cell types, including neurons, carrying the genetic background of the donor and enabling de novo generation of human models of genetically complex disorders. Parkinson's disease (PD) is the second most common age-related progressive neurodegenerative disease, which is mainly characterized by nigrostriatal dopaminergic (DA) neuron degeneration and synaptic dysfunction. Recently, the generation of disease-specific iPSC from patients suffering from PD has unveiled a recapitulation of disease-related cell phenotypes, such as abnormal α-synuclein accumulation and alterations in autophagy machinery. The use of patient-specific iPSC has a remarkable potential to uncover novel insights of the disease pathogenesis, which in turn will open new avenues for clinical intervention. This review explores the current Parkinson's disease iPSC-based models highlighting their role in the discovery of new drugs, as well as discussing the most challenging limitations iPSC-models face today

Vaccination with an HIV T-cell immunogen induces alterations in the mouse gut microbiota

The gut microbiota is emerging as a crucial factor modulating vaccine responses; however, few studies have investigated if vaccines, in turn, can alter the microbiota and to what extent such changes may improve vaccine efficacy. To understand the effect of T-cell vaccination on the gut microbiome, we administered an HIV-1 T-cell immunogen (HTI arm) or PBS (control, Mock arm) to C57Bl/6 mice following a heterologous prime-boost scheme. The longitudinal dynamics of the mice gut microbiota was characterized by 16 S ribosomal RNA sequencing in fecal samples collected from cages, as well as from three gut sections (cecum, small and large intestine). Serum and spleen cells were obtained at the last time point of the study to assess immune correlates using IFNγ ELISPOT and cytokine Luminex ® assays. Compared with Mock, HTI-vaccinated mice were enriched in Clostridiales genera (Eubacterium xylanophilum group, Roseburia and Ruminococcus) known as primary contributors of anti-inflammatory metabolites, such as short-chain fatty acids. Such shift was observed after the first HTI dose and remained throughout the study follow-up (18 weeks). However, the enriched Clostridiales genera were different between feces and gut sections. The abundance of bacteria enriched in vaccinated animals positively correlated with HTI-specific T-cell responses and a set of pro-inflammatory cytokines, such as IL-6. This longitudinal analysis indicates that, in mice, T-cell vaccination may promote an increase in gut bacteria known to produce anti-inflammatory molecules, which in turn correlate with proinflammatory cytokines, suggesting an adaptation of the gut microbial milieu to T-cell-induced systemic inflammation

Probiotic effects on immunity and microbiome in HIV-1 discordant patients

Some HIV-1 infected patients are unable to completely recover normal CD4+ T-cell (CD4+) counts after achieving HIV-1 suppression with combined Antiretroviral Therapy (cART), hence being classified as immuno-discordant. The human microbiome plays a crucial role in maintaining immune homeostasis and is a potential target towards immune reconstitution. RECOVER (NCT03542786) was a double-blind placebo-controlled clinical trial designed to evaluate if the novel probiotic i3.1 (AB-Biotics, Sant Cugat del Vallès, Spain) was able to improve immune reconstitution in HIV-1 infected immuno-discordant patients with stable cART and CD4+ counts <500 cells/mm3. The mixture consisted of two strains of L. plantarum and one of P. acidilactici, given with or without a fiber-based prebiotic. 71 patients were randomized 1:2:2 to Placebo, Probiotic or probiotic + prebiotic (Synbiotic), and were followed over 6 months + 3-month washout period, in which changes on systemic immune status and gut microbiome were evaluated. Primary endpoints were safety and tolerability of the investigational product. Secondary endpoints were changes on CD4+ and CD8+ T-cell (CD8+) counts, inflammation markers and faecal microbiome structure, defined by alpha diversity (Gene Richness), beta diversity (Bray-Curtis) and functional profile. Comparisons across/within groups were performed using standard/paired Wilcoxon test, respectively. Adverse event (AE) incidence was similar among groups (53%, 33%, and 55% in the Placebo, Probiotic and Synbiotic groups, respectively, the most common being grade 1 digestive AEs: flatulence, bloating and diarrhoea. Two grade 3 AEs were reported, all in the Synbiotic group: abdominal distension (possibly related) and malignant lung neoplasm (unrelated), and 1 grade 4 AE in the Placebo: hepatocarcinoma (unrelated). Synbiotic exposure was associated with a higher increase in CD4+/CD8+ T-cell (CD4/CD8) ratio at 6 months vs baseline (median=0.76(IQR=0.51) vs 0.72(0. 45), median change= 0.04(IQR=0.19), p = 0.03). At month 9, the Synbiotic group had a significant increase in CD4/CD8 ratio (0.827(0.55) vs 0.825(0.53), median change = 0.04(IQR=0.15), p= 0.02) relative to baseline, and higher CD4+ counts (447 (157) vs. 342(73) counts/ml, p = 0.03), and lower sCD14 values (2.16(0.67) vs 3.18(0.8), p = 0.008) than Placebo. No effect in immune parameters was observed in the Probiotic arm. None of the two interventions modified microbial gene richness (alpha diversity). However, intervention as categorical variable was associated with slight but significant effect on Bray-Curtis distance variance (Adonis R2 = 0.02, p = 0.005). Additionally, at month 6, Synbiotic intervention was associated with lower pathway abundances vs Placebo of Assimilatory Sulphate Reduction (8.79·10 -6 (1.25·10 -5) vs. 1.61·10 -5 (2.77·10 -5), p = 0.03) and biosynthesis of methionine (2.3·10 -5 (3.17·10 -5) vs. 4·10 -5 (5.66·10 -5), p = 0.03) and cysteine (1.83·10 -5 (2.56·10 -5) vs. 3.3·10 -5 (4.62·10 -5), p = 0.03). At month 6, probiotic detection in faeces was associated with significant decreases in C Reactive Protein (CRP) vs baseline (11.1(22) vs. 19.2(66), median change= -2.7 (13.2) ug/ml, p = 0.04) and lower IL-6 values (0.58(1.13) vs. 1.17(1.59) ug/ml, p = 0.02) when compared with samples with no detectable probiotic. No detection of the probiotic was associated with higher CD4/CD8 ratio at month 6 vs baseline (0.718(0.57) vs. 0.58(0.4), median change = 0.4(0.2), p = 0.02). After washout, probiotic non-detection was also associated with a significant increase in CD4+ counts (457(153) vs. 416(142), median change = 45(75), counts/ml, p = 0.005) and CD4/CD8 ratio (0.67(0.5) vs 0.59(0.49), median change = 0.04 (0.18), p = 0.02). A synbiotic intervention with L. plantarum and P. acidilactici was safe and led to small increases in CD4/CD8 ratio and minor reductions in sCD14 of uncertain clinical significance. A probiotic with the same composition was also safe but did not achieve any impact on immune parameters or faecal microbiome composition

Probiotic effects on immunity and microbiome in HIV-1 discordant patients

BackgroundSome HIV-1 infected patients are unable to completely recover normal CD4+ T-cell (CD4+) counts after achieving HIV-1 suppression with combined Antiretroviral Therapy (cART), hence being classified as immuno-discordant. The human microbiome plays a crucial role in maintaining immune homeostasis and is a potential target towards immune reconstitution.SettingRECOVER (NCT03542786) was a double-blind placebo-controlled clinical trial designed to evaluate if the novel probiotic i3.1 (AB-Biotics, Sant Cugat del Vallès, Spain) was able to improve immune reconstitution in HIV-1 infected immuno-discordant patients with stable cART and CD4+ counts &lt;500 cells/mm3. The mixture consisted of two strains of L. plantarum and one of P. acidilactici, given with or without a fiber-based prebiotic.Methods71 patients were randomized 1:2:2 to Placebo, Probiotic or probiotic + prebiotic (Synbiotic), and were followed over 6 months + 3-month washout period, in which changes on systemic immune status and gut microbiome were evaluated. Primary endpoints were safety and tolerability of the investigational product. Secondary endpoints were changes on CD4+ and CD8+ T-cell (CD8+) counts, inflammation markers and faecal microbiome structure, defined by alpha diversity (Gene Richness), beta diversity (Bray-Curtis) and functional profile. Comparisons across/within groups were performed using standard/paired Wilcoxon test, respectively.ResultsAdverse event (AE) incidence was similar among groups (53%, 33%, and 55% in the Placebo, Probiotic and Synbiotic groups, respectively, the most common being grade 1 digestive AEs: flatulence, bloating and diarrhoea. Two grade 3 AEs were reported, all in the Synbiotic group: abdominal distension (possibly related) and malignant lung neoplasm (unrelated), and 1 grade 4 AE in the Placebo: hepatocarcinoma (unrelated). Synbiotic exposure was associated with a higher increase in CD4+/CD8+ T-cell (CD4/CD8) ratio at 6 months vs baseline (median=0.76(IQR=0.51) vs 0.72(0. 45), median change= 0.04(IQR=0.19), p = 0.03). At month 9, the Synbiotic group had a significant increase in CD4/CD8 ratio (0.827(0.55) vs 0.825(0.53), median change = 0.04(IQR=0.15), p= 0.02) relative to baseline, and higher CD4+ counts (447 (157) vs. 342(73) counts/ml, p = 0.03), and lower sCD14 values (2.16(0.67) vs 3.18(0.8), p = 0.008) than Placebo. No effect in immune parameters was observed in the Probiotic arm. None of the two interventions modified microbial gene richness (alpha diversity). However, intervention as categorical variable was associated with slight but significant effect on Bray-Curtis distance variance (Adonis R2 = 0.02, p = 0.005). Additionally, at month 6, Synbiotic intervention was associated with lower pathway abundances vs Placebo of Assimilatory Sulphate Reduction (8.79·10-6 (1.25·10-5) vs. 1.61·10-5 (2.77·10-5), p = 0.03) and biosynthesis of methionine (2.3·10-5 (3.17·10-5) vs. 4·10-5 (5.66·10-5), p = 0.03) and cysteine (1.83·10-5 (2.56·10-5) vs. 3.3·10-5 (4.62·10-5), p = 0.03). At month 6, probiotic detection in faeces was associated with significant decreases in C Reactive Protein (CRP) vs baseline (11.1(22) vs. 19.2(66), median change= -2.7 (13.2) ug/ml, p = 0.04) and lower IL-6 values (0.58(1.13) vs. 1.17(1.59) ug/ml, p = 0.02) when compared with samples with no detectable probiotic. No detection of the probiotic was associated with higher CD4/CD8 ratio at month 6 vs baseline (0.718(0.57) vs. 0.58(0.4), median change = 0.4(0.2), p = 0.02). After washout, probiotic non-detection was also associated with a significant increase in CD4+ counts (457(153) vs. 416(142), median change = 45(75), counts/ml, p = 0.005) and CD4/CD8 ratio (0.67(0.5) vs 0.59(0.49), median change = 0.04 (0.18), p = 0.02).ConclusionA synbiotic intervention with L. plantarum and P. acidilactici was safe and led to small increases in CD4/CD8 ratio and minor reductions in sCD14 of uncertain clinical significance. A probiotic with the same composition was also safe but did not achieve any impact on immune parameters or faecal microbiome composition

π-Conjugated molecules with fused rings for organic field-effect transistors: design, synthesis and applications

π-Conjugated molecular materials with fused rings are the focus of considerable interest in the emerging area of organic electronics, since the combination of excellent charge carrier mobility and high stability may lead to their practical applications. This tutorial review discusses the synthesis, properties and applications of π-conjugated organic semiconducting materials, especially those with fused rings. The achievements to date, the remaining problems and challenges, and the key research that needs to be done in the near future are all discussed

Using iPS Cells toward the Understanding of Parkinson’s Disease

Cellular reprogramming of somatic cells to human pluripotent stem cells (iPSC) represents an efficient tool for in vitro modeling of human brain diseases and provides an innovative opportunity in the identification of new therapeutic drugs. Patient-specific iPSC can be differentiated into disease-relevant cell types, including neurons, carrying the genetic background of the donor and enabling de novo generation of human models of genetically complex disorders. Parkinson’s disease (PD) is the second most common age-related progressive neurodegenerative disease, which is mainly characterized by nigrostriatal dopaminergic (DA) neuron degeneration and synaptic dysfunction. Recently, the generation of disease-specific iPSC from patients suffering from PD has unveiled a recapitulation of disease-related cell phenotypes, such as abnormal α-synuclein accumulation and alterations in autophagy machinery. The use of patient-specific iPSC has a remarkable potential to uncover novel insights of the disease pathogenesis, which in turn will open new avenues for clinical intervention. This review explores the current Parkinson’s disease iPSC-based models highlighting their role in the discovery of new drugs, as well as discussing the most challenging limitations iPSC-models face today

Using pacient-specific IPSC derived dopaminergic to investigate Parkinson's disease: a new prospective in stem cell research and application = Utilització de neurones dopaminèrgiques específiques de pacients derivades de cèl·lules pluripotents induïdes (IPSC) en la investigació de la malaltia de Parkinson: una nova perspectiva en la investigació amb cèl·lules mare i les seves aplicacions

[eng] Parkinson’s disease (PD) is an incurable neurodegenerative disorder, mainly characterized by a progressive loss of midbrain dopaminergic (DA) neurons, located in the substantia nigra pars compacta (SNpc), and frequently accompanied by the formation of insoluble cytosolic protein aggregates in the remaining surviving neurons, known as Lewy bodies. The progressive denervation of DA terminals that project to the basal ganglia striatum causes a lack of DA uptaking, and consequently a progressive manifestation of debilitating motor deficits, that leads to premature invalidity and death. To date, only symptomatic therapies can compensate efficiently the locomotor deficiencies over a period of 5 years, however they do not cure or halt disease progression. A lack of suitable animal and cellular models might explain the fragmentary knowledge of the pathogenic mechanisms leading to PD, and highlights the urgent need for developing reliable experimental models that can recapitulate the key features of this disorder. The utilization of induced pluripotent stem cells (iPSC) offers an unprecedented opportunity to model human diseases, since they can be generated from patients and differentiated into disease-relevant cell types, such as neurons. Recently, human iPSC-based models of PD have been described. iPSC-derived neurons from patients with familial and sporadic PD recapitulate human disease phenotypes in vitro such as abnormal α-synuclein accumulation, and alterations in the autophagy machinery. Here, we investigated the neuroprotective effect of several compounds, including the neurotrophic factor GDNF, in culture of iPSC-derived midbrain dopaminergic neurons from patients with a LRKK2 mutation or sporadic patients. Interestingly, we found that six weeks after GDNF treatment, the level of dendritic arborisation from DA neurons derived from ID-PD and LRRK2-PD-iPSC increased to normal levels found in Ctrl-iPSC derived DA neurons. The neuroprotective effects were associated to a decrease in the number of apoptotic cells, and to a GFR1α/RET downstream activation of cell survival pathways, as well as reduction of autophagosome vesicles, compared to the untreated PD-iPSC derived DA neurons. Additionally, we found that GDNF is, in part, a requirement for a properly systemic neuronal survival in this model, since levels of GDNF were found twice decreased within long-term DAn cultures derived from both ID-PD and LRRK2-PD, when compared to CTL. In conclusion, our data demonstrate that iPSC-derived neuronal cells are valuable models for measuring responses to neuroprotective therapies and they may help to identify potential new drugs, thus furthering the development of treatments for PD. The differential secretion of survival factors within the culture also highlights the importance of using this technology for studying the contribution of other neural cell types in the onset of PD.[cat] La malaltia de Parkinson (MP) és un desordre neurodegeneratiu incurable, principalment caracteritzat per la pèrdua progressiva de neurones dopaminèrgiques (DA) del mesencèfal, localitzades a la substancia nigra pars compacta (SNpc), i freqüentment acompanyat per la formació d’agregats proteics citosòlics insolubles en les neurones supervivents residuals, coneguts com a cossos de Lewy. La progressiva denervació dels terminals dopaminèrgics que projecten als ganglis basals i l’estriat causa una manca d’alliberament i ús de dopamina, provocant com a conseqüència una progressiva manifestació de dèficits motors, que acaben conduïnt a la invalidesa i mort prematura. Actualment, la MP només es pot tractar amb teràpies simptomàtiques que compensen eficientment les deficiències locomotores durant un període al voltant dels 5 anys. No obstant, les teràpies existents no permeten curar ni aturar la progressió de la malaltia. La manca de models animals i cel·lulars adequats podrien explicar el coneixement fragmentari dels mecanismes patològics que condueixen a la MP, i posa en relleu la necessitat urgent de desenvolupar models experimentals fiables que puguin recapitular les principals característiques d’aquest trastorn. L’ús de cèl·lules mare amb pluripotència induïda (iPSC) ofereix una oportunitat sense precedents per a modelar malalties humanes, ja que poden ser generades a partir de pacients i diferenciades en tipus cel·lulars rellevants de la malaltia. Recentment, s’han descrit models basats en iPSC humanes per a l’estudi de la MP. Neurones derivades de iPSC provinents de pacients amb MP familiar i esporàdica recapitulen fenotips humans específics de la malaltia in vitro, com ara l’acumulació anormal d’α-sinucleïna, i alteracions en la maquinària de l’autofàgia. En aquesta tesi doctoral s’ha investigat l’efecte neuroprotectiu de diferents compostos, incloent el factor neurotròfic GDNF, en el cultiu in vitro de neurones DA derivades de iPSC de pacients amb la mutació familiar G2019S al gen lrrk2 (LRRK2-PD), i pacients esporàdics (ID-PD). Curiosament, s’ha trobat que sis setmanes després del tractament amb el GDNF, el nivell d’arborització dendrítica de les neurones DA derivades de LRRK2-PD i ID-PD-iPSC augmentà fins als nivells normals trobats en les neurones DA derivades d’individus control (Ctrl-iPSC). En comparació amb els cultius neuronals DA derivats de PD-iPSC sense el tractament, els efectes neuroprotectius estaven associats a una disminució en el número de neurones apoptòtiques, i a l’activació de vies de supervivència cel·lular, riu avall del complex receptor del GDNF GFR1α/RET, així com també la reducció de vesícules autofàgiques. A més, s’ha trobat que el GDNF és, en part, un requisit per a una correcta supervivència neuronal sistèmica en aquest model. Concretament, els nivells de GDNF a llarg temps de cultiu es troben dos vegades disminuïts tant en els cultius DA de ID-PD com els de LRRK2-PD, en comparació amb els nivells de les Ctrl. En conclusió, els nostres resultats demostren que les cèl·lules neuronals derivades de iPSC són models valuosos per a mesurar respostes a teràpies neuroprotectives, i per tant poden ajudar a identificar nous fàrmacs potencials, fomentant així el desenvolupament de tractaments per a la MP. La secreció diferencial de factors de supervivència dins del cultiu també destaca l’importància de l’ús d’aquesta tecnologia per a l’estudi de la contribució d’altres tipus neurals en la patogènesis de la MP

Using pacient-specific IPSC derived dopaminergic to investigate Parkinson's disease: a new prospective in stem cell research and application = Utilització de neurones dopaminèrgiques específiques de pacients derivades de cèl·lules pluripotents induïdes (IPSC) en la investigació de la malaltia de Parkinson: una nova perspectiva en la investigació amb cèl·lules mare i les seves aplicacions

Parkinson’s disease (PD) is an incurable neurodegenerative disorder, mainly characterized by a progressive loss of midbrain dopaminergic (DA) neurons, located in the substantia nigra pars compacta (SNpc), and frequently accompanied by the formation of insoluble cytosolic protein aggregates in the remaining surviving neurons, known as Lewy bodies. The progressive denervation of DA terminals that project to the basal ganglia striatum causes a lack of DA uptaking, and consequently a progressive manifestation of debilitating motor deficits, that leads to premature invalidity and death. To date, only symptomatic therapies can compensate efficiently the locomotor deficiencies over a period of 5 years, however they do not cure or halt disease progression. A lack of suitable animal and cellular models might explain the fragmentary knowledge of the pathogenic mechanisms leading to PD, and highlights the urgent need for developing reliable experimental models that can recapitulate the key features of this disorder. The utilization of induced pluripotent stem cells (iPSC) offers an unprecedented opportunity to model human diseases, since they can be generated from patients and differentiated into disease-relevant cell types, such as neurons. Recently, human iPSC-based models of PD have been described. iPSC-derived neurons from patients with familial and sporadic PD recapitulate human disease phenotypes in vitro such as abnormal α-synuclein accumulation, and alterations in the autophagy machinery. Here, we investigated the neuroprotective effect of several compounds, including the neurotrophic factor GDNF, in culture of iPSC-derived midbrain dopaminergic neurons from patients with a LRKK2 mutation or sporadic patients. Interestingly, we found that six weeks after GDNF treatment, the level of dendritic arborisation from DA neurons derived from ID-PD and LRRK2-PD-iPSC increased to normal levels found in Ctrl-iPSC derived DA neurons. The neuroprotective effects were associated to a decrease in the number of apoptotic cells, and to a GFR1α/RET downstream activation of cell survival pathways, as well as reduction of autophagosome vesicles, compared to the untreated PD-iPSC derived DA neurons. Additionally, we found that GDNF is, in part, a requirement for a properly systemic neuronal survival in this model, since levels of GDNF were found twice decreased within long-term DAn cultures derived from both ID-PD and LRRK2-PD, when compared to CTL. In conclusion, our data demonstrate that iPSC-derived neuronal cells are valuable models for measuring responses to neuroprotective therapies and they may help to identify potential new drugs, thus furthering the development of treatments for PD. The differential secretion of survival factors within the culture also highlights the importance of using this technology for studying the contribution of other neural cell types in the onset of PD.La malaltia de Parkinson (MP) és un desordre neurodegeneratiu incurable, principalment caracteritzat per la pèrdua progressiva de neurones dopaminèrgiques (DA) del mesencèfal, localitzades a la substancia nigra pars compacta (SNpc), i freqüentment acompanyat per la formació d’agregats proteics citosòlics insolubles en les neurones supervivents residuals, coneguts com a cossos de Lewy. La progressiva denervació dels terminals dopaminèrgics que projecten als ganglis basals i l’estriat causa una manca d’alliberament i ús de dopamina, provocant com a conseqüència una progressiva manifestació de dèficits motors, que acaben conduïnt a la invalidesa i mort prematura. Actualment, la MP només es pot tractar amb teràpies simptomàtiques que compensen eficientment les deficiències locomotores durant un període al voltant dels 5 anys. No obstant, les teràpies existents no permeten curar ni aturar la progressió de la malaltia. La manca de models animals i cel·lulars adequats podrien explicar el coneixement fragmentari dels mecanismes patològics que condueixen a la MP, i posa en relleu la necessitat urgent de desenvolupar models experimentals fiables que puguin recapitular les principals característiques d’aquest trastorn. L’ús de cèl·lules mare amb pluripotència induïda (iPSC) ofereix una oportunitat sense precedents per a modelar malalties humanes, ja que poden ser generades a partir de pacients i diferenciades en tipus cel·lulars rellevants de la malaltia. Recentment, s’han descrit models basats en iPSC humanes per a l’estudi de la MP. Neurones derivades de iPSC provinents de pacients amb MP familiar i esporàdica recapitulen fenotips humans específics de la malaltia in vitro, com ara l’acumulació anormal d’α-sinucleïna, i alteracions en la maquinària de l’autofàgia. En aquesta tesi doctoral s’ha investigat l’efecte neuroprotectiu de diferents compostos, incloent el factor neurotròfic GDNF, en el cultiu in vitro de neurones DA derivades de iPSC de pacients amb la mutació familiar G2019S al gen lrrk2 (LRRK2-PD), i pacients esporàdics (ID-PD). Curiosament, s’ha trobat que sis setmanes després del tractament amb el GDNF, el nivell d’arborització dendrítica de les neurones DA derivades de LRRK2-PD i ID-PD-iPSC augmentà fins als nivells normals trobats en les neurones DA derivades d’individus control (Ctrl-iPSC). En comparació amb els cultius neuronals DA derivats de PD-iPSC sense el tractament, els efectes neuroprotectius estaven associats a una disminució en el número de neurones apoptòtiques, i a l’activació de vies de supervivència cel·lular, riu avall del complex receptor del GDNF GFR1α/RET, així com també la reducció de vesícules autofàgiques. A més, s’ha trobat que el GDNF és, en part, un requisit per a una correcta supervivència neuronal sistèmica en aquest model. Concretament, els nivells de GDNF a llarg temps de cultiu es troben dos vegades disminuïts tant en els cultius DA de ID-PD com els de LRRK2-PD, en comparació amb els nivells de les Ctrl. En conclusió, els nostres resultats demostren que les cèl·lules neuronals derivades de iPSC són models valuosos per a mesurar respostes a teràpies neuroprotectives, i per tant poden ajudar a identificar nous fàrmacs potencials, fomentant així el desenvolupament de tractaments per a la MP. La secreció diferencial de factors de supervivència dins del cultiu també destaca l’importància de l’ús d’aquesta tecnologia per a l’estudi de la contribució d’altres tipus neurals en la patogènesis de la MP