Neurogenic Differentiation Research Articles

Ligandrol Ameliorates High-Fat Diet- and Streptozotocin-Induced Type 2 Diabetes Mellitus and Prevents Pancreatic Islets Degeneration.

Androgen therapy has been shown to alleviate type 2 diabetes mellitus (T2DM) but is also associated with severe side effects such as prostate cancer. The present study aims to identify the best hit selective androgen receptor (AR) modulator by in silico studies and then investigates its antidiabetic effects in high-fat diet- and streptozotocin (STZ)-induced T2DM male rat model. Molecular docking and molecular dynamics (MD) studies were carried out using Maestro 13.1 and Desmond (2023-2024). Cytotoxicity and insulin secretion were measured in MIN6 cell lines. T2DM was induced using high-fat diet (HFD) for 4 weeks, followed by single STZ (40 mg/kg, intraperitoneally). OneTouch Ultra glucometer was used to measure fasting blood glucose. Gene expression was determined using reverse transcription polymerase chain reaction. Histopathology was carried out using hematoxylin and eosin stain. Through molecular docking, we identify ligandrol as a potential hit. Ligandrol showed a good binding affinity (-10.74 kcal/mol). MD showed that ligandrol is stable during the 100 ns simulation. Ligandrol increases insulin secretion in a dose-dependent manner in vitro in 2 h. Ligandrol (0.3 and 1 mg/kg, orally) significantly decreased the body weight and fasting blood glucose levels compared with the HFD and STZ group. Gene expression showed that ligandrol significantly increased the AR-targeted gene, neurogenic differentiation 1, compared with the HFD and STZ group. Histopathological staining studies showed that ligandrol prevents pancreatic islet degeneration compared with the HFD and STZ group. Our findings suggest that ligandrol's protective effect on pancreatic islets leading to its antidiabetic effect occurs through the activation of AR.

Application prospects of urine-derived stem cells in neurological and musculoskeletal diseases.

Urine-derived stem cells (USCs) are derived from urine and harbor the potential of proliferation and multidirectional differentiation. Moreover, USCs could be reprogrammed into pluripotent stem cells [namely urine-derived induced pluripotent stem cells (UiPSCs)] through transcription factors, such as octamer binding transcription factor 4, sex determining region Y-box 2, kruppel-like factor 4, myelocytomatosis oncogene, and Nanog homeobox and protein lin-28, in which the first four are known as Yamanaka factors. Mounting evidence supports that USCs and UiPSCs possess high potential of neurogenic, myogenic, and osteogenic differentiation, indicating that they may play a crucial role in the treatment of neurological and musculoskeletal diseases. Therefore, we summarized the origin and physiological characteristics of USCs and UiPSCs and their therapeutic application in neurological and musculoskeletal disorders in this review, which not only contributes to deepen our understanding of hallmarks of USCs and UiPSCs but also provides the theoretical basis for the treatment of neurological and musculoskeletal disorders with USCs and UiPSCs.

Mechanotransductive N-cadherin binding induces differentiation in human neural stem cells

The neural stem cell niche is a complex microenvironment that includes cellular factors, secreted factors, and physical factors that impact stem cell behavior and development. Cellular interactions through cadherins, cell–cell binding proteins, have implications in embryonic development and mesenchymal stem cell differentiation. However, little is known about the influence of cadherins within the neural stem cell microenvironment and their effect on human stem cell maintenance and differentiation. Therefore, the purpose of this study was to develop synthetic substrates to examine the effect of cadherin mechanotransduction on human neural stem cells. Glass substrates were fabricated using silane, protein A, and recombinant N-cadherin; we used these substrates to examine the effect of N-cadherin binding on neural stem cell proliferation, cytoskeletal structure and morphology, Yes-associated protein-1 (YAP) translocation, and differentiation. Bound exogenous N-cadherin induced concentration-dependent increases in adherens junction formation, YAP translocation, and early expression of neurogenic differentiation markers. Strong F-actin ring structures were initiated by homophilic N-cadherin binding, eliciting neuronal differentiation of cells within 96 ​h without added soluble differentiation factors. Our findings show that active N-cadherin binding plays an important role for differentiation of human iPS-derived neural stem cells towards neurons, providing a new tool to differentiate cells in vitro.

KDM2B and its peptides promote the stem cells from apical papilla mediated nerve injury repair in rats by intervening EZH2 function.

How to improve the neurogenic potential of mesenchymal stem cells (MSCs) and develop biological agent based on the underlying epigenetic mechanism remains a challenge. Here, we investigated the effect of histone demethylase Lysine (K)-specific demethylase 2B (KDM2B) on neurogenic differentiation and nerve injury repair by using MSCs from dental apical papilla (SCAP). We found that KDM2B promoted the neurogenic indicators expression and neural spheres formation in SCAP, and modified the Histone H3K4 trimethylation (H3K4me3) methylation on neurogenesis-related genes. KDM2B improved the SCAP mediated recovery of motor ability at the early healing stage of spinal cord injury rats. Meanwhile, KDM2B acted as a negative regulator to its partner EZH2 during neurogenic differentiation, enhancer of zeste homologue 2 (EZH2) suppressed the neurogenic ability of SCAP. Further, the protein interaction between KDM2B and EZH2 was identified which decreased during neurogenic differentiation. On this basis, we revealed seven key protein binding sequences of KDM2B to EZH2, and synthesized KDM2B-peptides based on these sequences. By the usage of KDM2B-peptides, EZH2 function was effectively intervened and the neurogenic ability of SCAP was promoted. More, KDM2B-peptides significantly improved the SCAP mediated functional recovery at SCI early phase. Our study revealed that KDM2B acted as a promotor to neurogenic differentiation ability of dental MSCs through binding and negatively regulating EZH2, and provided the KDM2B-peptides as candidate agents for improving the neurogenic ability of MSCs and nerve injury repair.

Garlic Extract Promotes Pancreatic Islet Neogenesis Through α-to-β-Cell Transdifferentiation and Normalizes Glucose Homeostasis in Diabetic Rats.

Garlic extract (GE) has been shown to ameliorate hyperglycemia in diabetic rats (DRs) by increasing insulin production. However, the mechanism through which it exerts its effects remains unclear. Here, it investigates the molecular process and the origin of regenerating β-cell in rats with streptozotocin (STZ)-induced diabetes in response to GE. In this study, quantitative RT-PCR (qRT-PCR), western blotting, and immunohistochemical analysis are carried out after pancreas isolation. These findings show that 1 week of GE treatment increases the expression of the endocrine progenitor cell markers Neurogenin3 (Neurog3), pancreatic and duodenal homeobox 1 (Pdx1), neurogenic differentiation factor 1 (Neurod1), paired box proteins (Pax)4, V-maf musculoaponeurotic fibrosarcoma oncogene homolog B(Mafb),and NK homeobox factors (Nkx)6-1 in STZ-induced DRs. Continuation with GE treatment for 8 weeks causes the expression of the mature β-cell markers insulin(Ins)2, urocortin3 (Ucn3), and glucose transporter 2 (Glut2) to peak. Comprehensive examination of the islet through immunohistochemical analysis reveals the presence of a heterogeneous cell population including INS+/GLUT2- and INS+/GLUT2+ β-cell subpopulations with few bihormonal INS+/GCG+ cells after 4 weeks. By week 8, islet architecture is reestablished, and glucose-stimulated insulin secretion was restored through the upregulation of Ucn3. GE induces β-cell neogenesis in DRs and restores islet architecture. The newly formed mature β-like cells could have originated through the differentiation of endocrine progenitor cells as well as α- to β-cell transdifferentiation.

Injectable dual drug-loaded thermosensitive liposome-hydrogel composite scaffold for vascularised and innervated bone regeneration

Adequate blood supply and thorough innervation are essential to the survival of tissue-engineered bones. Though great progress has been created in the application of bone tissue engineering technology to bone defect repair, many challenges remain, such as insufficient vascularisation and deficient innervation in newly regenerated bone. In the present study, we addressed these challenges by manipulating the bone regeneration microenvironment in terms of vascularisation and innervation. We used a novel injectable thermosensitive liposome-hydrogel composite scaffold as a sustained-release carrier for basic fibroblast growth factor (bFGF, which promotes angiogenesis and neurogenic differentiation) and dexamethasone (Dex, which promotes osteogenic differentiation). In vitro biological assessment demonstrated that the composite scaffold had sufficient cell compatibility; it enhanced the capacity for angiogenesis in human umbilical vein endothelial cells, and the capacity for neurogenic/osteogenic differentiation in human bone marrow mesenchymal stem cells. Moreover, the introduction of bFGF/Dex liposome-hydrogel composite scaffold to bone defect sites significantly improved vascularisation and innervated bone regeneration properties in a rabbit cranial defect model. Based on our findings, the regeneration of sufficiently vascularised and innervated bone tissue through a sustained-release scaffold with excellent injectability and body temperature sensitivity represents a promising tactic towards bone defect repair.

Characteristics of molecular subtypes and cinical outcomes in the immunotherapy Queue of extensive-stage small cell lung cancer patients

BackgroundWith a series of clinical trials confirming the sensitivity of small cell lung cancer (SCLC) to immunotherapy, research on personalized treatment for SCLC has gained increasing attention. Currently, the most widely accepted subtype of SCLC is based on the expression levels of Achaete-Scute Family BHLH Transcription Factor 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), and POU class 2 homeobox 3 (POU2F3). However, real-world studies on this classification remain limited.MethodsWe retrospectively collected biopsy specimens from patients who received immunotherapy at Shandong Provincial Hospital between January 2019 and July 2021. After determining the patient subtypes using immunohistochemistry, we analyzed the relationships between each subtype and survival as well as some clinical characteristics.ResultsIn our study, we found that the subtype I achieved a significant survival advantage compared to the other groups. Additionally, the subtype A demonstrated a significant survival disadvantage. Among patients in the subtype I, there was a higher proportion of early brain metastasis and patients with a family history of tumors, while the subtype A had a lower proportion. Furthermore, the subtype A exhibited relatively poor immune infiltration.ConclusionIn a diverse cohort of SCLC patients receiving immunotherapy, the subtype-I showed significant survival advantages while the subtype-A experienced a worse survival.

Dominant Malignant Clones Leverage Lineage Restricted Epigenomic Programs to Drive Ependymoma Development.

1. Specific chromatin modules accessible during brain development render distinct cell lineage programs at risk of transformation by pediatric fusion oncoproteins.2. Cross-species single cell ATAC and RNA (scMultiome) of mouse and human ependymoma (EPN) reveals diverse patterns of lineage differentiation programs that restrain oncogenic transformation.3. Early intermediate progenitor-like EPN cells establish a tumor cell hierarchy that mirrors neural differentiation programs.4. ZFTA-RELA transformation is compatible with distinct developmental epigenetic states requiring precise 'goldilocks' levels of fusion oncoprotein expression.5. Dominant tumor clones establish the entire EPN cellular hierarchy that reflects normal gliogenic and neurogenic differentiation programs.

Optogenetics in oral and craniofacial research.

Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control, noninvasiveness, and high efficiency. Genetically modified photosensory sensors are engineered into proteins to modulate conformational changes with light stimulation. Therefore, optogenetic techniques can provide new insights into oral biological processes at different levels, ranging from the subcellular and cellular levels to neural circuits and behavioral models. Here, we introduce the origins of optogenetics and highlight the recent progress of optogenetic approaches in oral and craniofacial research, focusing on the ability to apply optogenetics to the study of basic scientific neural mechanisms and to establish different oral behavioral test models in vivo (orofacial movement, licking, eating, and drinking), such as channelrhodopsin (ChR), archaerhodopsin (Arch), and halorhodopsin from Natronomonas pharaonis (NpHR). We also review the synergic and antagonistic effects of optogenetics in preclinical studies of trigeminal neuralgia and maxillofacial cellulitis. In addition, optogenetic tools have been used to control the neurogenic differentiation of dental pulp stem cells in translational studies. Although the scope of optogenetic tools is increasing, there are limited large animal experiments and clinical studies in dental research. Potential future directions include exploring therapeutic strategies for addressing loss of taste in patients with coronavirus disease 2019 (COVID-19), studying oral bacterial biofilms, enhancing craniomaxillofacial and periodontal tissue regeneration, and elucidating the possible pathogenesis of dry sockets, xerostomia, and burning mouth syndrome.

Leading medulloblastoma to a differentiation end

Effective and less toxic therapies for medulloblastoma have proved to be highly elusive. In this issue of Cancer Cell, Yang etal. show that thyroid hormone treatment leads to the activation of neurogenic differentiation factor 1 (NeuroD1) and differentiation of medulloblastoma cells through reversing EZH2-mediated transcriptional repression of NeuroD1.

Shell-core structured nanofibers mediate staged anti-inflammatory and pro-neurogenic activities to repair peripheral nerve

The inflammatory reaction significantly impedes the neurogenic process during the restoration of peripheral nerve injury (PNI). Therefore, establishing a non-inflammatory environment is crucial for effective nerve regeneration. This study proposes the use of shell-core structured nanofibers with sequential anti-inflammatory and pro-neurogenic activities to repair PNI. Icariin (ICA), known for its anti-inflammatory effects, was blended with poly(lactic-co-glycolic acid) (PLGA) to form the shell layer’s spinning solution. Concurrently, glial cell-derived neurotrophic factor (GDNF) was combined with graphene oxide (GO) to create the core layer’s spinning solution. These solutions were then subjected to co-axial electrospinning, resulting in shell-core structured GDNF@GO-ICA@PLGA nanofibers. Additionally, a control group of unordered GDNF/GO/ICA/PLGA nanofibers was prepared using conventional electrospinning. The resulting GDNF@GO-ICA@PLGA nanofibers exhibited distinct fibrous structures with a clear shell-core architecture and demonstrated mechanical properties similar to the control group. Notably, the shell-core structured GDNF@GO-ICA@PLGA nanofibers displayed unique staged release kinetics: over 90% ICA was released priorly within the first 0 to 13 days, followed by GDNF release from days 9 to 31. Furthermore, the GDNF@GO-ICA@PLGA nanofibers showed excellent biocompatibility with Schwann cells. In vitro results highlighted the potent anti-inflammatory capabilities of ICA released from the shell layer, while GDNF released from the core layer effectively induced neurogenic differentiation of Schwann cells. The GDNF@GO-ICA@PLGA nanofibers were then processed into a nerve conduit and applied to a 10 mm rat sciatic PNI model. The staged release of ICA and GDNF facilitated by the GDNF@GO-ICA@PLGA nanofibers created a non-inflammatory environment before initiating nerve regeneration, leading to improved PNI restoration. This study underscores the importance of shell-core structured nanofibers in sequentially mediating anti-inflammation and neurogenesis, offering a novel approach for addressing PNI.

Human cytomegalovirus infection impairs neural differentiation via repressing sterol regulatory element binding protein 2-mediated cholesterol biosynthesis

Congenital human cytomegalovirus (HCMV) infection is a major cause of abnormalities and disorders in the central nervous system (CNS) and/or the peripheral nervous system (PNS). However, the complete pathogenesis of neural differentiation disorders caused by HCMV infection remains to be fully elucidated. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells (MSCs) with a high proliferation and neurogenic differentiation capacity. Since SHEDs originate from the neural crest of the early embryonic ectoderm, SHEDs were hypothesized to serve as a promising cell line for investigating the pathogenesis of neural differentiation disorders in the PNS caused by congenital HCMV infection. In this work, SHEDs were demonstrated to be fully permissive to HCMV infection and the virus was able to complete its life cycle in SHEDs. Under neurogenic inductive conditions, HCMV infection of SHEDs caused an abnormal neural morphology. The expression of stem/neural cell markers was also disturbed by HCMV infection. The impairment of neural differentiation was mainly due to a reduction of intracellular cholesterol levels caused by HCMV infection. Sterol regulatory element binding protein-2 (SREBP2) is a critical transcription regulator that guides cholesterol synthesis. HCMV infection was shown to hinder the migration of SREBP2 into nucleus and resulted in perinuclear aggregations of SREBP2 during neural differentiation. Our findings provide new insights into the prevention and treatment of nervous system diseases caused by congenital HCMV infection.

Role of the Stem Cells from Human Deciduous Teeth in Dentistry: A Review

ABSTRACT Stem cells isolated from human exfoliated deciduous teeth or SHED possess high rate of proliferation along with high osteogenic as well as neurogenic differentiation when compared with dental pulpal stem cells. This stem cell population is an important source for therapeutic regeneration of tissues. Hence, the aim of present review article was to analyze the potential applications of SHED.

Alginate-gelatin hydrogel promotes the neurogenic differentiation potential of bone marrow CD117+ hematopoietic stem cells

People still hold the concept of using cell-based treatments to regenerate missing neurons in high esteem. CD117+ cells are considered favorable stem cells for regenerative medicine. The objective of this research was to examine the impact of Alginate-Gelatin (Alg-Gel) hydrogel on the process of neurogenic differentiation of CD117+ cells utilizing a cytokines secretion test conducted in a laboratory setting. To achieve this objective, bone marrow-CD117+ cells were isolated using the MACS technique and then transformed into neuron cells using a neurogenic differentiation medium. The characterization of enriched CD117+ cells has been done with flow cytometry as well as immunocytochemistry. Next, the cells underwent western blotting assay to evaluate the signaling pathways. Subsequently, the culture media was obtained from both groups in order to determine cytokine levels. The study revealed that the Alg-Gel hydrogel had a notable impact on enhancing the protein expression of neuron markers such as β-tubulin and Wnt/catenin signaling pathway components in CD117+ neurogenic differentiated cells. Furthermore, the cultured medium from the experimental group exhibited a notable abundance of IL-6 and IL-10 in comparison to the control group. The observed in vitro effects of Alg-Gel hydrogel on neurogenic differentiation of CD117+ cells are likely to be caused by the cytokines that are released.

Exploring SSEA3 as an emerging biomarker for assessing the regenerative potential of dental pulp-derived stem cells

BackgroundHuman dental pulp-derived stem cells (hDPSCs) have emerged as a promising source for adult stem cell-based regenerative medicine. Stage-specific embryonic antigen 3 (SSEA3) is a cell surface marker associated with Multilineage-differentiating stress-enduring (Muse) cells, a subpopulation of human bone marrow-derived stem cells (hBMSCs), known for their potent regenerative potential and safety profile. In this study, we investigated the influence of the prolonged culture period and the number of culture passages on the regenerative capacity of hDPSCs and explored the association between SSEA3 expression and their regenerative abilities. MethodshDPSCs were isolated and cultured for up to 20 passages. Cell proliferation, migration, and osteogenic, adipogenic and neurogenic differentiation potential were assessed at passages 5, 10, and 20. Flow cytometry and immunofluorescence were employed to analyze SSEA3 expression. RNA sequencing (RNA-seq) was performed on SSEA3-positive and SSEA3-negative hDPSCs to identify differentially expressed genes and associated pathways. ResultsOur findings demonstrated a progressive decline in hDPSCs proliferation and migration capacity with increasing passage number. Conversely, cell size exhibited a positive correlation with passage number. Early passage hDPSCs displayed superior osteogenic and adipogenic differentiation potential. Notably, SSEA3 expression exhibited a significant negative correlation with passage numbers, reflecting the observed decline in differentiation capacity. RNA-seq analysis revealed distinct transcriptional profiles between SSEA3-positive and SSEA3-negative hDPSCs. SSEA3-positive cells displayed upregulation of genes associated with ectodermal differentiation and downregulation of genes involved in cell adhesion. ConclusionsThis study elucidates the impact of passaging on hDPSC behavior and suggests SSEA3 as a valuable biomarker for evaluating stemness and regenerative potential. SSEA3-positive hDPSCs, functionally analogous to Muse cells, represent a promising cell population for developing targeted regenerative therapies with potentially improved clinical outcomes.

Behavioral transcriptomic effects of triploidy and probiotic therapy (Bifidobacterium, Lactobacillus, and Lactococcus mixture) on juvenile Chinook salmon (Oncorhynchus tshawytscha).

Aquaculturists use polyploid fish to maximize production albeit with some unintended consequences including compromised behaviors and physiological function. Given benefits of probiotic therapies (e.g., improved immune response, growth, and metabolism), we explored probiotic supplementation (mixture of Bifidobacterium, Lactobacillus, and Lactococcus), to overcome drawbacks. We first examined fish gut bacterial community composition using 16S metabarcoding (via principal coordinate analyses and PERMANOVA) and determined probiotics significantly impacted gut bacteria composition (p = 0.001). Secondly, we examined how a genomic disruptor (triploidy) and diet supplements (probiotics) impact gene transcription and behavioral profiles of hatchery-reared Chinook salmon (Oncorhynchus tshawytscha). Juveniles from four treatment groups (diploid-regular feed, diploid-probiotic feed, triploid-regular feed, and triploid-probiotic feed; n = 360) underwent behavioral assays to test activity, exploration, neophobia, predator evasion, aggression/sociality, behavioral sensitivity, and flexibility. In these fish, transcriptional profiles for genes associated with neural functions (neurogenesis/synaptic plasticity) and biomarkers for stress response and development (growth/appetite) were (i) examined across treatments and (ii) used to describe behavioral phenotypes via principal component analyses and general linear mixed models. Triploids exhibited a more active behavioral profile (p = 0.002), and those on a regular diet had greater Neuropeptide Y transcription (p = 0.02). A growth gene (early growth response protein 1, p = 0.02) and long-term neural development genes (neurogenic differentiation factor, p = 0.003 and synaptysomal-associated protein 25-a, p = 0.005) impacted activity and reactionary profiles, respectively. Overall, our probiotic treatment did not compensate for triploidy. Our research highlights novel applications of behavioral transcriptomics for identifying candidate genes and dynamic, mechanistic associations with complex behavioral repertoires.

Integrated toxicity of secondary, tertiary, wetland effluents on human stem cells triggered by ERα and PPARγ agonists

Residual pollutants in discharged and reused water pose both direct and indirect human exposure. However, health effects caused by whole effluent remain largely unknown due to the lack of human relevant model for toxicity test. Effluents from four secondary wastewater treatment plants (SWTPs), a tertiary wastewater treatment plant (TWTP) and a constructed wetland (CW) were evaluated for the integrated toxicity of the organic extractions. Multiple-endpoint human mesenchymal stem cells (MSCs) assay was used as an in vitro model relevant to human health. The effluents caused cytotoxicity, oxidative stress and genotoxicity in MSCs. The osteogenic and neurogenic differentiation were inhibited and the adipogenic differentiation were stimulated by some of the effluent extractions. The SWTP, TWTP and CW treatments reduced integrated biomarker response (IBR) by 26.3 %, 17.5 % and 33.3 % respectively, where the IBR values of final CW (8.3) and TWTP (8.2) effluents were relatively lower than SWTPs (9.1). Among multiple biomarkers, the inhibition of osteogenesis was the least reduced by wastewater treatment. Besides, ozone disinfection in tertiary treatment increased cytotoxicity and differentiation effects suggesting the generation of toxic products. The mRNA expressions of estrogen receptor alpha (ERα) and peroxisome proliferator-activated receptor gamma (PPARγ) were significantly upregulated by effluents. The inhibitory effects of effluents on neural differentiation were mitigated after antagonizing ERα and PPARγ in the cells. It is suggested that ERα and PPARγ agonists in effluents were largely accountable for the impairment of stem cell differentiation. Besides, the concentrations of n-C29H60, o-cresol, fluorene and phenanthrene in the effluents were significantly correlated with the intergrated stem cell toxicity. The present study provided toxicological evidence for the relation between water contamination and human health, with an insight into the key toxicity drivers. The necessity for deep water treatment and the potential means were suggested for improving water quality.

Biomimetic bone-periosteum scaffold for spatiotemporal regulated innervated bone regeneration and therapy of osteosarcoma

The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.

Melatonin Enhances Neural Differentiation of Adipose-Derived Mesenchymal Stem Cells.

Adipose-derived mesenchymal stem cells (ASCs) are adult multipotent stem cells, able to differentiate toward neural elements other than cells of mesodermal lineage. The aim of this research was to test ASC neural differentiation using melatonin combined with conditioned media (CM) from glial cells. Isolated from the lipoaspirate of healthy donors, ASCs were expanded in a basal growth medium before undergoing neural differentiation procedures. For this purpose, CM obtained from olfactory ensheathing cells and from Schwann cells were used. In some samples, 1 µM of melatonin was added. After 1 and 7 days of culture, cells were studied using immunocytochemistry and flow cytometry to evaluate neural marker expression (Nestin, MAP2, Synapsin I, GFAP) under different conditions. The results confirmed that a successful neural differentiation was achieved by glial CM, whereas the addition of melatonin alone did not induce appreciable changes. When melatonin was combined with CM, ASC neural differentiation was enhanced, as demonstrated by a further improvement of neuronal marker expression, whereas glial differentiation was attenuated. A dynamic modulation was also observed, testing the expression of melatonin receptors. In conclusion, our data suggest that melatonin's neurogenic differentiation ability can be usefully exploited to obtain neuronal-like differentiated ASCs for potential therapeutic strategies.

Development of Anisotropic Electrically Conductive GNP-Reinforced PCL-Collagen Scaffold for Enhanced Neurogenic Differentiation under Electrical Stimulation.

The internal electric field of the human body plays a crucial role in regulating various biological processes, such as, cellular interactions, embryonic development and the healing process. Electrical stimulation (ES) modulates cytoskeleton and calcium ion activities to restore nervous system functioning. When exposed to electrical fields, stem cells respond similarly to neurons, muscle cells, blood vessel linings, and connective tissue (fibroblasts), depending on their environment. This study develops cost-effective electroconductive scaffolds for regenerative therapy. This was achieved by incorporating carboxy functionalized graphene nanoplatelets (GNPs) into a Polycaprolactone (PCL)-collagen matrix. ES was used to assess the scaffolds' propensity to boost neuronal differentiation from MSCs. This study reported that aligned GNP-reinforced PCL-Collagen scaffolds demonstrate substantial MSC differentiation with ES. This work effectively develops scaffolds using a simple, cost-effective synthesis approach. The direct coupling approach generated a homogeneous electric field to stimulate cells cultured on GNP-reinforced scaffolds. The scaffolds exhibited improved mechanical and electrical characteristics, as a result of the reinforcement with carbon nanofillers. In vitro results suggest that electrical stimulation helps differentiation of mesenchymal stem-like cells (MSC-like) towards neuronal. This finding holds great potential for the development of effective treatments for tissue injuries related to the nervous system.