Proliferation Of Stem Cells Research Articles

An Efficient Endothelial Cell Differentiation Protocol Using Bioactive Lipid O-Cyclic Phytosphingosine-1-Phosphate in Human Embryonic Stem Cells.

Bioactive lipids like sphingosine-1-phosphate (S1P) and lysophosphatidic acid have gained significant attention as signaling molecules with regulatory roles in stem cell proliferation and differentiation. The novel chemically synthesized sphingosine metabolite O-cyclic phytosphingosine-1-phosphate (cP1P) is derived from phytosphingosine-1-phosphate (P1P) and shares structural similarities with S1P. Previously, the role of cP1P in regulating ALK3/BMPR signaling during cardiomyocyte differentiation from human embryonic stem cells (hESCs) was demonstrated. In this study, the applicability of cP1P for endothelial cells (ECs) differentiation from hESCs was investigated an efficient method to obtain a high yield of functional ECs over several passages was standardized. The ECs derived from hESCs showed cellular and molecular characteristics similar to the native ECs. Thus, the results of this study open avenues for further research into cP1P-based stem cell differentiation for regenerative therapies.

Ginger-Derived Extracellular Vesicles: A Natural Solution for Alopecia.

Ginger (Zingiber officinale (L.) Rosc), as an edible plant-derived nanoparticle, offers several advantages, such as a high return rate, low budget, no ethical barriers, and good for health. Ginger-Derived Extracellular Vesicles (GDEVs) are nanoscale vesicles isolated from ginger. In this study, GDEVs were used to treat the alopecia mouse model, and its main active components and potential mechanism of action were investigated. The LC-MS/MS analysis of GDEVs revealed the presence of 1299 chemical compounds, among which auxiliary components were identified. Interestingly, the crux of the analysis lies in the discovery of 13 specific ingredients that play a pivotal role in hair proliferation. The aim of this study was to investigate the protective effect of GDEVs on hair loss. These advantages make ginger-derived nanoparticles a promising solution to overcome technical limitations associated with mammalian nanoparticles. This study elucidates the mechanism of action of GDEVs in the treatment of alopecia. However, the active ingredients and mechanism of action of GDEVs in the treatment of hair loss are unknown. GDEVs were isolated from ginger using the differential centrifugal method. Network pharmacological analysis of the GDEVs revealed that the anti-hair loss effect of GDEVs on alopecia was closely linked to its ability to reduce inflammation and promote the proliferation of hair follicle stem cells. Subsequently, it was applied to the balding areas of hair-loss mice using a brush. The results demonstrated that the application of GDEVs led to a rapid recovery of the balding areas and promoted the growth of healthier hair. This experiment reported that GDEVs can effectively suppress the inflammatory activity in the alopecia model mice.

Ginsenoside Re promotes proliferation of murine bone marrow mesenchymal stem cells in vitro through estrogen-like action.

Ginsenoside Re (GS-Re) is a major saponin monomer found in Panax ginseng Meyer. It has been shown to exhibit a wide range of biological and pharmacological activities. This study aimed to investigate the effect of GS-Re on the proliferation of murine bone marrow-derived MSCs in vitro and to assess whether its effect is dependent on the estrogen receptor-mediated signal transduction. CFU colony formation assay, cell counting, and colorimetric MTT test were employed to examine effects of GS-Re on the in vitro proliferation of MSCs and the mechanisms of the underlying effect were detected by flow cytometric analysis, immunofluorescence staining for BrdU, and Western blotting. GS-Re dose-dependently promoted the in vitro proliferation of murine bone marrow-derived MSCs over a range of concentrations of 0.5 ~ 20µmol/L, and this effect approached the maximal level at 10µmol/L. Increases in the expression level of phosphorylated extracellular signal-regulated kinases 1/2 (p-ERK1/2) were observed in the passaged MSCs treated with 10µmol/L of GS-Re. These effects of GS-Re on the MSCs were significantly counteracted by the addition of ICI 182, 780 (an estrogen receptor antagonist) to the culture media. We concluded that GS-Re is able to exert a proliferation-promoting effect on murine bone marrow-derived mesenchymal stem cells in vitro, and its action is involved in the estrogen receptor-mediated signaling.

Hydrogel Microsphere-Encapsulated Bimetallic Nanozyme for Promoting Diabetic Bone Regeneration via Glucose Consumption and ROS Scavenging.

The healing of bone defects among diabetic patients presents a critical challenge due to the pathological microenvironment, characterized by hyperglycemia, excessive reactive oxygen species (ROS) production, and inflammation. Herein, multifunctional composite microspheres, termed GMAP are developed, using a microfluidic technique by incorporating Au@Pt nanoparticles (NPs) and GelMA hydrogel to modulate the diabetic microenvironment for promoting bone regeneration. The GMAP enables the sustained release of Au@Pt NPs, which function as bimetallic nanozymes with dual enzyme-like activities involving glucose oxidase and catalase. The synergistic effect allows for efficient glucose consumption and ROS elimination concurrently. Thus, the GMAP effectively protects the proliferation of bone marrow mesenchymal stem cells (BMSCs) under adverse high-glucose conditions. Furthermore, it also promotes the osteogenic differentiation and paracrine capabilities of BMSCs, and subsequently inhibits inflammation and enhances angiogenesis. In vivo diabetic rats bone defect model, it is demonstrated that GMAP microspheres significantly improve bone regeneration, as verified by micro-computed tomography and histological examinations. This study provides a novel strategy for bone regeneration by modulating the diabetic microenvironment, presenting a promising approach for addressing the complex challenges associated with bone healing in diabetic patients.

Hypoxia and loss of GCM1 expression prevents differentiation and contact inhibition in human trophoblast stem cells.

The placenta develops alongside the embryo and nurtures fetal development to term. During the first stages of embryonic development, due to low blood circulation, the blood and ambient oxygen supply is very low (~1-2% O2) and gradually increases upon placental invasion. While a hypoxic environment is associated with stem cell self-renewal and proliferation, persistent hypoxia may have severe effects on differentiating cells and could be the underlying cause of placental disorders. We find that human trophoblast stem cells (hTSC) thrive in low oxygen, whereas differentiation of hTSC to trophoblast to syncytiotrophoblast (STB) and extravillous trophoblast (EVT) is negatively affected by hypoxic conditions. The pro-differentiation factor GCM1 (human Glial Cell Missing-1) is downregulated in low oxygen, and concordantly there is substantial reduction of GCM1-regulated genes in hypoxic conditions. Knockout of GCM1 in hTSC caused impaired EVT and STB formation and function, reduced expression of differentiation-responsive genes, and resulted in maintenance of self-renewal genes. Treatment with a PI3K inhibitor reported to reduce GCM1 protein levels likewise counteracts spontaneous or directed differentiation. Additionally, chromatin immunoprecipitation of GCM1 showed enrichment of GCM1-specific binding near key transcription factors upregulated upon differentiation including the contact inhibition factor CDKN1C. Loss of GCM1 resulted in downregulation of CDKN1C and corresponding loss of contact inhibition, implicating GCM1 in regulation of this critical process.

Osteogenic potentials in canine mesenchymal stem cells: unraveling the efficacy of polycaprolactone/hydroxyapatite scaffolds in veterinary bone regeneration

BackgroundThe integration of stem cells, signaling molecules, and biomaterial scaffolds is fundamental for the successful engineering of functional bone tissue. Currently, the development of composite scaffolds has emerged as an attractive approach to meet the criteria of ideal scaffolds utilized in bone tissue engineering (BTE) for facilitating bone regeneration in bone defects. Recently, the incorporation of polycaprolactone (PCL) with hydroxyapatite (HA) has been developed as one of the suitable substitutes for BTE applications owing to their promising osteogenic properties. In this study, a three-dimensional (3D) scaffold composed of PCL integrated with HA (PCL/HA) was prepared and assessed for its ability to support osteogenesis in vitro. Furthermore, this scaffold was evaluated explicitly for its efficacy in promoting the proliferation and osteogenic differentiation of canine bone marrow-derived mesenchymal stem cells (cBM-MSCs) to fill the knowledge gap regarding the use of composite scaffolds for BTE in the veterinary orthopedics field.ResultsOur findings indicate that the PCL/HA scaffolds substantially supported the proliferation of cBM-MSCs. Notably, the group subjected to osteogenic induction exhibited a markedly upregulated expression of the osteogenic gene osterix (OSX) compared to the control group. Additionally, the construction of 3D scaffold constructs with differentiated cells and an extracellular matrix (ECM) was successfully imaged using scanning electron microscopy. Elemental analysis using a scanning electron microscope coupled with energy-dispersive X-ray spectroscopy confirmed that these constructs possessed the mineral content of bone-like compositions, particularly the presence of calcium and phosphorus.ConclusionsThis research highlights the synergistic potential of PCL/HA scaffolds in concert with cBM-MSCs, presenting a multidisciplinary approach to scaffold fabrication that effectively regulates cell proliferation and osteogenic differentiation. Future in vivo studies focusing on the repair and regeneration of bone defects are warranted to further explore the regenerative capacity of these constructs, with the ultimate goal of assessing their potential in veterinary clinical applications.

Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish: unveiling the role of vascular endothelial growth factor signaling and microglia.

After brain damage, regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals, suggesting a close link between these processes. However, the mechanisms by which these processes interact are not well understood. In this work, we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury. To this end, we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms. First, using the Tg(fli1:EGFP × mpeg1.1:mCherry) zebrafish line, which enables visualization of blood vessels and microglia respectively, we analyzed regenerative angiogenesis from 1 to 21 days post-lesion. In parallel, we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry. We found that after brain damage, the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor (vegfaa and vegfbb) were increased. At the same time, neural stem cell proliferation was also increased, peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis, along with the recruitment of microglia. Then, through pharmacological manipulation by injecting an anti-angiogenic drug (Tivozanib) or Vegf at the lesion site, we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes, as well as microglial recruitment. Finally, we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis, as previously described, as well as injury-induced angiogenesis. In conclusion, we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process. In addition, we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes. This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.

Development of electrospun electroactive polyurethane membranes for bone repairing.

To fabricate electroactive fibrous membranes and provide simulated bioelectric micro-environment for bone regeneration mimicking nature periosteum, a series of electroactive polyurethanes (PUAT) were synthesized using amino-capped aniline trimers (AT) and lysine derivatives as chain extenders. These PUAT were fabricated into fibrous membranes as guided bone tissue regeneration membranes (GBRMs) via electrospinning. The ultraviolet-visible (UV-vis) absorption spectroscopy and cyclic voltammetry (CV) of PUAT copolymers showed that the electroactive PUAT fibrous membranes had good electroactivity. Besides, the introduction of AT significantly improved the hydrophobicity and thermal stability of PUAT fibrous membranes and decreased the degradation rate of PUAT fibers in vitro. With the increasing content of AT incorporated into copolymers, the tensile strength and Young's modulus of PUAT fibrous membranes increased from 4MPa (PUAT0) to 15MPa (PUAT10) and from 2.1MPa (PUAT0) to 18MPa (PUAT10), respectively. The cell morphology and proliferation of rat mesenchymal stem cells (rMSCs) on PUAT fibers indicated that the incorporation of AT enhanced the cell attachment and proliferation. Moreover, the expression levels of OCN, CD31, and VEGF secreted by rMSCs on PUAT fibers increased with the increasing content of AT. In conclusion, an electroactive polyurethane fibrous membrane mimicking natural periosteum was prepared via electrospinning and showed good potential application in guiding bone tissue regeneration.

Developments of Fms-like Tyrosine Kinase 3 Inhibitors as Anticancer Agents for AML Treatment.

FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated gene in acute myeloid leukemia. As a receptor tyrosine kinase (RTK), FLT3 plays a role in the proliferation and differentiation of hematopoietic stem cells. As the most frequent molecular alteration in AML, FLT3 has drawn the attention of many researchers, and a lot of small molecule inhibitors targeting FLT3 have been intensively investigated as potential drugs for AML therapy. In this paper, PubMed and SciFinder® were used as a tool; the publications about "FLT3 inhibitor" and "Acute myeloid leukemia" were surveyed from 2014 to the present with an exclusion of those published as patents. In this study, the structural characterization and biological activities of representative FLT3 inhibitors were summarized. The major challenges and future directions for further research are discussed. Recently, numerous FLT3 inhibitors have been discovered and employed in FLT3-mutated AML treatment. In order to overcome the drug resistance caused by FLT3 mutations, screening multitargets FLT3 inhibitors has become the main research direction. In addition, the emergence of irreversible FLT3 inhibitors also provides new ideas for discovering new FLT3 inhibitors.

P21-76 Effects of tobacco heating products on viability, proliferation and cytokine production of mesenchymal stem cells isolated from periodontal ligament

P21-76 Effects of tobacco heating products on viability, proliferation and cytokine production of mesenchymal stem cells isolated from periodontal ligament

Lovastatin Combination Therapy Increases the Survival and Proliferation of Rat Bone Marrow-Derived Mesenchymal Stem Cells Against the Inflammatory Activity of Lipopolysaccharide.

Oxidative stress hurts the survival of transplanted mesenchymal stem cells (MSCs). Lipopolysaccharide (LPS) preconditioning inhibits apoptotic death in MSCs. Also, Lovastatin's protective effect was reported on MSCs. Here, we investigated the potential of LPS and Lovastatin combination therapy on the survival and proliferation of MSCs. MSCs harvested from adult rats (240-260 g) femur and tibia bone marrow. Third passage MSCs were divided into 6 groups control group, LPS, LPS + Lovastatin (10 and 15 µM), and Lovastatin (10 and 15 µM). Cell survival and proliferation were assessed using an MTT assay 24 h after LPS, Lovastatin, or LPS + Lovastatin treatment. Also, Malondialdehyde (MDA) as a lipid peroxidation marker and antioxidant enzymes such as Glutathione peroxidase (GPX) and Superoxide dismutase (SOD) activity levels evaluated. Finally, the expression level of tumor protein P53 (P53) and octamer-binding transcription factor 4 (OCT4) genes were measured by qRT-PCR test. Lovastatin 10 μM potentiated proliferation and survival of MSCs. It can increase the activity of GPX and SOD. 10 µM Lovastatin could not affect MDA amounts but decreased the expression levels of P53 and Oct4 significantly. Nevertheless, treatment with LPS reduced the survival and proliferation of MSCs, along with a significant reduction in GPX activity. LPS + Lovastatin could increase SOD activity, however, GPX enzyme activity and MSCs proliferation did not change so, and it was not effective. We propose Lovastatin at the dose of 10 µM as a suitable combination agent to increase the survival and proliferation of MSCs in oxidative stress conditions.

Chios gum mastic enhance the proliferation and odontogenic differentiation of human dental pulp stem cells.

Dental pulp stem cells (DPSCs) are a type of adult stem cell present in the dental pulp tissue. They possess a higher proliferative capacity than bone marrow mesenchymal stem cells. Their ease of collection from patients makes them well-suited for tissue engineering applications, such as tooth and nerve regeneration. Chios gum mastic (CGM), a resin extracted from the stems and leaves of Pistacia lentiscus var. Chia, has garnered attention for its potential in tissue regeneration. This study aims to confirm alterations in cell proliferation rates and induce differentiation in human DPSCs (hDPSCs) through CGM treatment, a substance known for effectively promoting odontogenic differentiation. Administration of CGM to hDPSC cells was followed by an assessment of cell survival, proliferation, and odontogenic differentiation through protein and gene analysis. The study revealed that hDPSCs exhibited low sensitivity to CGM toxicity. CGM treatment induced cell proliferation by activating cell-cycle proteins through the Wnt/β-catenin pathway. Additionally, the study demonstrated that CGM enhances alkaline phosphatase activation by upregulating the expression of collagen type I, a representative matrix protein of dentin. This activation of markers associated with odontogenic and bone differentiation ultimately facilitated the mineralization of hDPSCs. This study concludes that CGM, as a natural substance, fosters the cell cycle and cell proliferation in hDPSCs. Furthermore, it triggers the transcription of odontogenic and osteogenic markers, thereby facilitating odontogenic differentiation.

Effect of platelet-rich fibrin and concentrated growth factor on the regenerative potential of human-induced pluripotent stem cells: A comparative analysis.

Platelet-rich fibrin (PRF) has been used, while concentrated growth factor (CGF) has recently evolved as a bioscaffold in regenerative endodontics. This study aimed to evaluate the effect of PRF and CGF on the proliferation, migration, and differentiation of human-induced pluripotent stem cells (hiPSCs). CGF and PRF were fabricated from voluntarily donated human blood, and a conditioned medium was prepared. HiPSCs were isolated and cultivated on a conditioned medium for 12 days. The proliferation rate was analyzed using a trypan blue assay on days 9, 10, and 11. The migratory rate was evaluated using a wound healing assay after 24, 48, and 72 h. For assessing the differentiation of hiPSCs, various markers with quantitative real-time polymerase chain reactions on day 12 were used. Mesenchymal phenotypic transition was seen with an increase in proliferation rate in the PRF group more than in the CGF group on day 9, along with the differentiation of cells with an increase in osteoblastic markers on day 12 in both groups. The migratory capacity of cells was significantly increased in the CGF and PRF groups, with a greater increase in the CGF group. CGF and PRF extend the duration of growth factor activity and enhance cell proliferation and osteogenic differentiation, with hiPSCs serving as a bioscaffold with high regenerative potential.

Gasdermin D Mediated Mitochondrial Metabolism Orchestrate Neurogenesis Through LDHA During Embryonic Development.

Regulatory cell death is an important way to eliminate the DNA damage that accompanies the rapid proliferation of neural stem cells during cortical development, including pyroptosis, apoptosis, and so on. Here, the study reports that the absence of GSDMD-mediated pyroptosis results in defective DNA damage sensor pathways accompanied by aberrant neurogenesis and autism-like behaviors in adult mice. Furthermore, GSDMD is involved in organizing the mitochondrial electron transport chain by regulating the AMPK/PGC-1α pathway to target Aifm3. This process promotes a switch from oxidative phosphorylation to glycolysis. The perturbation of metabolic homeostasis in neural progenitor cells increases lactate production which acts as a signaling molecule to regulate the p38MAPK pathway. And activates NF-𝜿B transcription to disrupt cortex development. This abnormal proliferation of neural progenitor cells can be rescued by inhibiting glycolysis and lactate production. Taken together, the study proposes a metabolic axis regulated by GSDMD that links pyroptosis with metabolic reprogramming. It provides a flexible perspective for the treatment of neurological disorders caused by genotoxic stress and neurodevelopmental disorders such as autism.

The role of vitamin D in multiple sclerosis and its mechanisms of action

Introduction and Purpose: Multiple sclerosis (MS) is a prevalent autoimmune disease affecting the central nervous system, particularly in young people. Characterized by neurodegenerative and demyelinating processes, MS is influenced by genetic and environmental factors. Research indicates that sufficient levels of vitamin D can reduce the risk of developing MS. Studies show that higher sun exposure and dietary vitamin D intake are associated with a lower incidence of MS. Moreover, vitamin D supplementation may benefit those already diagnosed by alleviating symptoms and improving their quality of life. This review explores the potential benefits of vitamin D and its neuroprotective mechanisms in MS. State of Knowledge: MS research and treatments have focused on immunomodulation, with less emphasis on neuroprotection, including the role of vitamin D. It is well-established that vitamin D has anti-inflammatory effects on the immune system in MS. It influences the proliferation and differentiation of neural stem cells and oligodendrocytes, enhances neurotrophin expression, reduces reactive astrogliosis, decreases oxidative stress, and stabilizes the blood-brain barrier. Research suggests that adequate vitamin D levels and supplementation might improve MS outcomes. Conclusion: New diagnostic tools and therapeutic strategies are urgently needed to address the complex nature of MS, which includes inflammation, neuronal death, demyelination, and oxidative stress. Promoting vitamin D sufficiency and supplementation, alongside developing new neuroprotective agents, remains a valuable approach in combating MS. Understanding the mechanisms of MS and the effects of vitamin D could lead to better management strategies and enhanced quality of life for patients.

The Impact of the VEGF/VEGFR2/PI3K/AKT Signaling Axis on the Proliferation and Migration Abilities of Human Dental Pulp Stem Cells.

The potential therapeutic benefits of human dental pulp stem cells (HDPSCs) in dental regenerative medicine have been demonstrated. However, little is known about the molecular mechanisms regulating the biological characteristics of HDPSCs. The experiment aims to explore whether VEGF activates signaling pathways such as FAK, PI3K, Akt, and p38 in HDPSCs, and to investigate the molecular mechanisms by which VEGF influences proliferation and migration of HDPSCs. Normal and inflamed human dental pulp (HDP) samples were collected, and the levels of VEGF in HDP were assessed. HDPSCs were cultured and purified. HDPSCs were stimulated with lipopolysaccharide (LPS) at gradient concentrations, and real-time quantitative polymerase chain reaction (qPCR) was used to assess changes in VEGF mRNA. Gradient concentrations of VEGF were used to stimulate HDPSCs, and cell migration ability was evaluated through scratch assays and Transwell chamber experiments. Phosphorylation levels of FAK, AKT, and P38 were assessed using Western blotting. Inhibitors of VEGFR2, FAK, AKT, P38, and VEGF were separately applied to HDPSCs, and cell migration ability and phosphorylation levels of FAK, AKT, and P38 were determined. The results indicated significant differences in VEGF levels between normal and inflamed HDP tissues, with levels in the inflamed state reaching 435% of normal levels (normal: 87.91 ng/mL, inflamed: 382.76 ng/mL, P < 0.05). LPS stimulation of HDPSCs showed a significant increase in VEGF mRNA expression with increasing LPS concentrations (LPS concentrations of 0.01, 0.1, 1, and 10 μg/mL resulted in VEGF mRNA expressions of 181.2%, 274.2%, 345.8%, and 460.9%, respectively, P < 0.05). VEGF treatment significantly enhanced the migration ability of HDPSCs in Transwell chamber experiments, with migration rates increasing with VEGF concentrations (VEGF concentrations of 0, 1, 10, 20, 50, and 100 ng/mL resulted in migration rates of 8.41%, 9.34%, 21.33%, 28.41%, 42.87%, and 63.15%, respectively, P < 0.05). Inhibitors of VEGFR2, FAK, AKT, P38, and combined VEGF stimulation demonstrated significant migration inhibition, with migration rates decreasing to 8.31%, 12.64%, 13.43%, 18.32%, and 74.17%, respectively. The migration rate with combined VEGF stimulation showed a significant difference (P < 0.05). The analysis of phosphorylation levels revealed that VEGF stimulation significantly activated phosphorylation of FAK, AKT, and P38, with phosphorylation levels increasing with VEGF concentrations (P < 0.05). The VEGF/VEGFR2 signaling axis regulated the migration ability of HDPSCs through the FAK/PI3K/AKT and P38MAPK pathways. This finding highlighted not only the crucial role of VEGF in injury repair of HDPSCs but also provided important clues for a comprehensive understanding of the potential applications of this signaling axis in dental regenerative medicine.

Creating an extracellular matrix-like three-dimension structure to enhance the corrosion resistance and biological responses of titanium implants

Background/purposeTitanium (Ti) is extensively used in dental and orthopedic implants due to its excellent mechanical properties. However, its smooth and biologically inert surface does not support the ingrowth of new bone, and Ti ions may have adverse biological effects. The purpose is to improve the corrosion resistance of titanium and create a 3D structured coating to enhance osseointegration through a very simple and fast surface treatment. Materials and methodsThis study investigated the use of sandblasting, acid etching, and NaOH leaching to produce porous Ti implants with enhanced biological activity and corrosion resistance. ResultsThese surface modifications generated a mixed oxide layer resembling the extracellular matrix (ECM), consisting of a dense amorphous TiO2 inner layer (50–100 nm thick) and a TiO2 outer layer with interconnected pores (pore size 50–500 nm; 150–200 nm thick). The inner layer significantly improved corrosion resistance, while the hydrophilic outer layer, with its porous structure, facilitated protein albumin adsorption and promoted the attachment, proliferation, and mineralization of human bone marrow mesenchymal stem cells. ConclusionThe combined surface treatment approach of sandblasting, acid etching, and NaOH leaching offers a comprehensive solution to the challenges associated with titanium implants' biological inertness and corrosion susceptibility. By enhancing both the biological activity and corrosion resistance of Ti surfaces, this protocol holds significant promise for improving dental and orthopedic implants' success rates and longevity. Future studies should focus on in vivo assessments and long-term clinical trials to further validate these findings and explore the potential for widespread clinical adoption.

Xyloglucan, alginate and k-carrageenan hydrogels on spheroids of adipose stem cells survival; preparation, mechanical characterization, morphological analysis and injectability

The therapeutic capabilities of autologous stem cells can be fully exploited if their survival after implantation is improved.For the first time, we compared three hydrogels, with different chemical structure, morphology, and viscoelastic properties, where the same differentiation factors were immobilized and spheroids from adipose stem cells (SASCs) were incorporated. The aim is to understand if hydrogel characteristics could influence the viability of the embedded stem cells. Specifically, hydrogels of partially degalactosylated xyloglucan (dXG), sodium alginate (Alg) and k-carrageenan (kC) were produced. The structure of the networks was probed by swelling/erosion measurements, rheological and morphological analysis. Cell viability was measured after 7 and 21 days. When SASCs were incubated under stemness conditions, dXG and kC hydrogels provide the optimal environment for cell viability. When incubated in the chondrogenic or osteogenic medium, a clear correlation was found between the storage and loss moduli and cell viability. Hydrogels with the lowest shear stiffness promote stem-cell differentiation and proliferation. The systems, particularly dXG, seem more similar to natural ECM and able to recreate niches, that colonized with stem cells could represent a real support in regenerative therapies. The injectability of formulations was evaluated to determine if they could be used for minimally invasive regenerative medicine interventions.

Evaluation of the Composite Skin Patch Loaded with Bioactive Functional Factors Derived from Multicellular Spheres of EMSCs for Regeneration of Full-thickness Skin Defects in Rats.

Transplantation of stem cells/scaffold is an efficient approach for treating tissue injury including full-thickness skin defects. However, the application of stem cells is limited by preservation issues, ethical restriction, low viability, and immune rejection in vivo. The mesenchymal stem cell conditioned medium is abundant in bioactive functional factors, making it a viable alternative to living cells in regeneration medicine. Nasal mucosa-derived ecto-mesenchymal stem cells (EMSCs) of rats were identified and grown in suspension sphere-forming 3D culture. The EMSCs-conditioned medium (EMSCs-CM) was collected, lyophilized, and analyzed for its bioactive components. Next, fibrinogen and chitosan were further mixed and cross-linked with the lyophilized powder to obtain functional skin patches. Their capacity to gradually release bioactive substances and biocompatibility with epidermal cells were assessed in vitro. Finally, a full-thickness skin defect model was established to evaluate the therapeutic efficacy of the skin patch. The EMSCs-CM contains abundant bioactive proteins including VEGF, KGF, EGF, bFGF, SHH, IL-10, and fibronectin. The bioactive functional composite skin patch containing EMSCs-CM lyophilized powder showed the network-like microstructure could continuously release the bioactive proteins, and possessed ideal biocompatibility with rat epidermal cells in vitro. Transplantation of the composite skin patch could expedite the healing of the full-thickness skin defect by promoting endogenous epidermal stem cell proliferation and skin appendage regeneration in rats. In summary, the bioactive functional composite skin patch containing EMSCs-CM lyophilized powder can effectively accelerate skin repair, which has promising application prospects in the treatment of skin defects.

Novel Chitosan-Gelatin Scaffold with Valproic Acid Augments In Vitro Osteoblast Differentiation of Mesenchymal Stem Cells.

The study aimed to develop a biodegradable scaffold incorporating valproic acid (VPA) for improved human bone marrow-derived mesenchymal stem cell (hBMSC) proliferation, differentiation, and bone mineral synthesis. A chitosan-gelatin (CH-G) scaffold was fabricated and loaded with varying concentrations of VPA (1, 3, 5 mM/L). In vitro studies assessed drug release, cell proliferation, morphology, mineralization, and gene expression. VPA was rapidly released from the scaffold, with over 90% cumulative release within seven days. Cells cultured on VPA-loaded scaffolds exhibited significantly enhanced proliferation and mineralization compared to the control. VPA treatment upregulated osteocalcin and runt-related transcription factor 2 (Runx-2) expression, key markers of osteogenic differentiation. The CH-G scaffold, particularly with 1 mM/L VPA, demonstrates excellent biocompatibility and promotes hBMSC-mediated bone regeneration. This novel approach holds promise for future applications in bone tissue engineering.