Potential Of Stem Cells Research Articles

Stem cell research and improving cancer treatments

Stem cell research has emerged as a pivotal area in oncology, offering innovative approaches to cancer treatment. This research explores the potential of stem cells to enhance therapeutic outcomes in various cancer types. To evaluate the role of stem cells in cancer treatment, focusing on their ability to differentiate into specialized cell types, promote tissue regeneration, and deliver targeted therapies. A comprehensive review of current literature was conducted, analyzing studies that investigate the application of stem cells in hematological malignancies and solid tumors. Key methodologies included in vitro experiments, animal models, and clinical trials assessing stem cell therapies, including hematopoietic stem cell transplantation and mesenchymal stem cell-based therapies. Findings indicate that stem cells can improve treatment efficacy by facilitating tumor regression, enhancing immune responses, and reducing treatment-related toxicity. Notably, mesenchymal stem cells have shown promise in delivering therapeutic agents directly to tumors and modulating the tumor microenvironment. Stem cell research holds significant potential to revolutionize cancer treatment strategies. Continued exploration of stem cell applications may lead to more effective, personalized therapies, ultimately improving patient outcomes in various cancer types. Further clinical trials are necessary to establish standardized protocols and assess long term effects.

Stem Cell Interventions in Neurology: From Bench to Bedside.

Stem cell therapies are progressively redefining the treatment landscape for a spectrum of neurological and age-related disorders. This review discusses the molecular and functional attributes of stem cells, emphasizing the roles of neural stem cells and mesenchymal stem cells in the context of neurological diseases such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson's disease, and Alzheimer's disease. The review also explores the potential of stem cells in addressing the aging process. The paper analyzes stem cells' intrinsic properties of self-renewal, differentiation, and paracrine effects, alongside the importance of laboratory-modified stem cells like induced pluripotent stem cells and transgenic stem cells. Insights into disease-specific stem cell treatments are offered, reviewing both successes and challenges in the field. This includes the translational difficulties from rodent studies to human trials. The review concludes by acknowledging the uncharted territories that warrant further investigation, emphasizing the potential roles of stem cell-derived exosomes and indole-related molecules, and aiming at providing a basic understanding of stem cell therapies.

A limbal stem cell deficiency murine model with residual limbal stem cells.

Bilateral limbal stem cell deficiency (LSCD) is a significant cause of corneal blindness and is more difficult to treat, as compared with unilateral LSCD because no source of autologous limbal stem cells (LSCs) remains in these patients. Thus, bilateral patients could be candidates for treatment with allogeneic LSC transplants that require long-term systemic immunosuppression therapy. Thus, if possible, for the correct candidates, using autologous LSCs could be a preferred treatment. Recent in vivo laser confocal microscopic examination of the ocular surface in situ , combined with impression cytology, has indicated that some patients diagnosed with a complete bilateral LSCD possess residual LSCs. However, it remains unknown whether these residual LSCs still have stem cell potential due to the lack of animal models that mimic this pathology. The goal of the current study is to make a complete LSCD model that possesses evidence of residual LSCs. We induced complete LSCD in mice using two methods: (1) removed the corneal epithelium and the epithelial basement membrane using a rotating burr, and (2) removed the corneal epithelium using 20% ethanol but retained an intact epithelial basement membrane. A complete LSCD was defined by a lack of CK12-positive corneal epithelial cells and the presence of infiltrating CK19-positive conjunctival epithelial cells. Corneas were examined for wound closure, corneal opacity, LSC exhaustion, and inflammation. We observed that complete LSCD mice without an intact epithelial basement membrane resulted in few residual LSCs. By contrast, complete LSCD mice that retained the epithelial basement membrane were accompanied by a reduced inflammatory response plus a significant number of residual LSCs. This model will allow future studies to determine the function of residual LSCs in complete LSCD.

Limited Adipogenic Differentiation Potential of Human Dental Pulp Stem Cells Compared to Human Bone Marrow Stem Cells.

Bone marrow and teeth contain mesenchymal stem cells (MSCs) that could be used for cell-based regenerative therapies. MSCs from these two tissues represent heterogeneous cell populations with varying degrees of lineage commitment. Although human bone marrow stem cells (hBMSCs) and human dental pulp stem cells (hDPSCs) have been extensively studied, it is not yet fully defined if their adipogenic potential differs. Therefore, in this study, we compared the in vitro adipogenic differentiation potential of hDPSCs and hBMSCs. Both cell populations were cultured in adipogenic differentiation media, followed by specific lipid droplet staining to visualise cytodifferentiation. The in vitro differentiation assays were complemented with the expression of specific genes for adipogenesis and osteogenesis-dentinogenesis, as well as for genes involved in the Wnt and Notch signalling pathways. Our findings showed that hBMSCs formed adipocytes containing numerous and large lipid vesicles. In contrast to hBMSCs, hDPSCs did not acquire the typical adipocyte morphology and formed fewer lipid droplets of small size. Regarding the gene expression, cultured hBMSCs upregulated the expression of adipogenic-specific genes (e.g., PPARγ2, LPL, ADIPONECTIN). Furthermore, in these cells most Wnt pathway genes were downregulated, while the expression of NOTCH pathway genes (e.g., NOTCH1, NOTCH3, JAGGED1, HES5, HEY2) was upregulated. hDPSCs retained their osteogenic/dentinogenic molecular profile (e.g., RUNX2, ALP, COLIA1) and upregulated the WNT-specific genes but not the NOTCH pathway genes. Taken together, our in vitro findings demonstrate that hDPSCs are not entirely committed to the adipogenic fate, in contrast to the hBMSCs, which are more effective to fully differentiate into adipocytes.

Overexpression of USP35 enhances the protective effect of hUC-MSCs and their extracellular vesicles in oxygen-glucose deprivation/reperfusion-induced SH-SY5Y cells via stabilizing FUNDC1

Ischemia-reperfusion (IR) injury is associated with neurological disorders such as stroke. The therapeutic potential of human umbilical cord mesenchymal stem cells (hUC-MSCs) and their secreted extracellular vesicles (EVs) in alleviating IR injury across various cell types including neuronal cells has been documented. However, the underlying mechanisms through which hUC-MSCs and hUC-MSC-EVs protect neuronal cells from IR-triggered damage are not well understood. In this study, we co-cultured SH-SY5Y neuroblastoma cells with hUC-MSCs or hUC-MSC-EVs and subjected them to oxygen-glucose deprivation/reperfusion (OGD/R) treatment. Our findings indicate that both hUC-MSCs and hUC-MSC-EVs significantly improved viability, reduced apoptosis, promoted autophagy of OGD/R-induced SH-SY5Y cells, and decreased mitochondrial reactive oxygen species levels within them. Furthermore, the neuroprotective effect of hUC-MSCs and hUC-MSC-EVs in OGD/R-induced SH-SY5Y cells was enhanced by overexpressing USP35, a deubiquitinase. Mechanistically, USP35 interacted with and stabilized FUNDC1, a positive regulator of mitochondrial metabolism. Knockdown of FUNDC1 in USP35-overexpressing hUC-MSCs and their secreted EVs eliminated the augmented neuroprotective function induced by excess USP35. In conclusion, these findings underscore the crucial role of USP35 in enhancing the neuroprotective function of hUC-MSCs and their secreted EVs, achieved through the stabilization of FUNDC1 in OGD/R-induced SH-SY5Y cells.

Therapeutic potential of mesenchymal stem cells and stem cell-derived extracellular vesicles in tuberculosis of various localizations: A review

Experimental and clinical studies using cell therapy are very popular. Mesenchymal stem cells (MSCs) and stem cell-derived extracellular vesicles (EV) are used as one of the components of therapy in these researches. The action of MSCs is mediated by the release of EV which play a direct role in the implementation of several important biological processes: angiogenesis, proliferation, modulation of the inflammatory process and immune response, inhibition of cellular apoptosis, etc. These properties of MSCs and stem cell-derived EV are of interest in the treatment of tuberculosis infection, because an integral part of the pathogenesis of tuberculosis is the creation of specific granulomas and the formation of fibrosis.

Promotion of bone osteogenic and regeneration by resveratrol-derived carbon dots in inflammatory environments via a one-step hydrothermal method

In the context of bone fractures, local inflammation complicates the healing process, adversely affecting the recovery of bone defects. This inflammatory response impedes the regenerative potential of stem cells and induces the differentiation of macrophages into the M1 type, thereby inhibiting bone regeneration. To address this issue, we synthesized carbon dots (CDs) using resveratrol and citric acid. These CDs demonstrated excellent water solubility and retained the anti-inflammatory properties of resveratrol. In an inflammatory environment co-cultured with resveratrol carbon dots (RES-CDs), we observed a reduction in inflammatory factors such as iNOS and an increase in anti-inflammatory factors like CD206. Alkaline phosphatase (ALP) activity, Alizarin Red staining, and immunofluorescence assays indicated that MC3T3 cells produced more calcium nodules after co-culture with RES-CDs, along with enhanced expression of bone formation factors BMP-2 and ALP. Additionally, real-time polymerase chain reaction (qRT-PCR) and immunofluorescence analysis demonstrated that RES-CDs could induce bone tissue proliferation and differentiation by upregulating ALP, BMP-2, OCN, and OPN. In a rat cranial defect model, RES-CDs promoted tissue healing and bone proliferation at weeks 1 and 4 post-surgery. These findings underscore the potential of resveratrol carbon dots in promoting bone tissue healing while mitigating inflammation, thereby offering a promising approach for nanocomposite materials in tissue repair.

Secretome from estrogen-responding human placenta-derived mesenchymal stem cells rescues ovarian function and circadian rhythm in mice with cyclophosphamide-induced primary ovarian insufficiency

BackgroundPrimary ovarian insufficiency (POI) is an early decline in ovarian function that leads to ovarian failure. Conventional treatments for POI are inadequate, and treatments based on mesenchymal stem cells (MSCs) have emerged as an option. However, the lack of consideration of the estrogen niche in ovarian tissue significantly reduces the therapeutic efficacy, with an unclear mechanism in the MSCs in POI treatment. Furthermore, the disruption of circadian rhythm associated with POI has not been previously addressed.MethodsConditioned medium (CM) and estradiol-conditioned medium (E2-CM) were generated from estrogen receptor positive MSCs (ER+pcMSCs). Chemotherapy-induced POI models were established using C57BL/6 mice (in vivo) and KGN cells (in vitro) treated with cyclophosphamide (CTX) or 4-hydroperoxycyclophosphamide (4-OOH-CP). Gene/protein expressions were detected using RT-qPCR, Western blotting, and immunohistochemistry assays. Locomotor activity was monitored for behavioral circadian rhythmicity. Cytokine arrays and miRNA analysis were conducted to analyze potential factors within CM/E2-CM.ResultsThe secretome of ER+pcMSCs (CM and E2-CM) significantly reduced the CTX-induced defects in ovarian folliculogenesis and circadian rhythm. CM/E2-CM also reduced granulosa cell apoptosis and rescued angiogenesis in POI ovarian tissues. E2-CM had a more favorable effect than the CM. Notably, ER+pcMSC secretome restored CTX-induced circadian rhythm defects, including the gene expressions associated with the ovarian circadian clock (e.g., Rora, E4bp4, Rev-erbα, Per2 and Dbp) and locomotor activity. Additionally, the cytokine array analysis revealed a significant increase in cytokines and growth factors associated with immunomodulation and angiogenesis, including angiogenin. Neutralizing the angiogenin in CM/E2-CM significantly reduced its ability to promote HUVEC tube formation in vitro. Exosomal miRNA analysis revealed the miRNAs involved in targeting the genes associated with POI rescue (PTEN and PDCD4), apoptosis (caspase-3, BIM), estrogen synthesis (CYP19A1), ovarian clock regulation (E4BP4, REV-ERBα) and fibrosis (COL1A1).ConclusionThis study is the first to demonstrate that, in considering the estrogen niche in ovarian tissue, an estrogen-priming ER+pcMSC secretome achieved ovarian regeneration and restored the circadian rhythm in a CTX-induced POI mouse model. The potential factors involved include angiogenin and exosomal miRNAs in the ER+pcMSC secretome. These findings offer insights into potential stem cell therapies for chemotherapy-induced POI and circadian rhythm disruption.

Selenium-doped carbon dots inhibit ferroptosis by multi-hierarchy iron chelation and mitochondrial homeostasis regulation to control inflammation

Ferroptosis has been identified as a prevalent pathological process in both infectious and non-infectious inflammation. Multiregional iron accumulation within extracellular, cytoplasmic, and subcellular compartments, particularly into mitochondria, can trigger lipid peroxidation and subsequent ferroptosis. Meanwhile, mitochondrial dysfunction, as a hallmark feature of ferroptosis, also exacerbates ferroptosis and inflammation. Here, a strategy of multi-hierarchy iron chelation coupled with mitochondrial homeostasis regulation is proposed to inhibit ferroptosis and relieve inflammation based on selenium-doped carbon dots (SeCDs). SeCDs with reactive oxygen species (ROS) scavenging capacity can be efficiently internalized into cells and enriched in mitochondria. Through the multi-hierarchy chelation for extracellular, cytoplasmic, and mitochondrial iron, iron overload is remarkably inhibited. Meanwhile, promoting glutathione peroxidase 4 (GPX4) expression and activating the AMPK pathway can restrain the metabolism of glycerophospholipids and polyunsaturated fatty acids and lipid peroxidation. Importantly, SeCDs restore mitochondrial homeostasis by chelating mitochondrial iron, scavenging mtROS, and increasing the level of GPX4, thereby enhancing ferroptosis suppression. Further, SeCDs rescue the osteogenic differentiation potential of stem cells, which is generally weakened by ferroptosis. In vivo experiments prove that SeCDs can significantly inhibit ferroptosis and inflammation, and facilitate tissue regeneration. Thus, this multifunctional nanosystem provides a promising therapeutic strategy to inhibit ferroptosis and ease inflammation.

Multi-omics analysis unveils the predictive value of IGF2BP3/SPHK1 signaling in cancer stem cells for prognosis and immunotherapeutic response in muscle-invasive bladder cancer

BackgroundMuscle invasive bladder cancer (MIBC) is a life-threatening malignant tumor characterized by high metastasis rates, poor prognosis, and limited treatment options. Immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 represent an emerging treatment for MIBC immunotherapy. However, the characteristics of patients likely to benefit from immunotherapy remain unclear.MethodsWe performed single-cell mass cytometry (CyTOF) analysis of 179,483 single cells to characterize potential immunotherapy-related cancer stem cells (CSCs)-like populations in the tumor microenvironment of 38 MIBC tissues. The upregulated expression of IGF2BP3 in CD274 + ALDH + CSC-like cells, which was associated with poor clinical prognosis, was analyzed by bulk RNA-sequencing data from an in-house cohort. The functional role of IGF2BP3 was determined through cell proliferation, colony formation, cell apoptosis and sphere formation assays. The regulation of SPHK1 expression by IGF2BP3 was investigated using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and bulk RNA-sequencing (bulk RNA-seq). We further utilized single-nucleus RNA sequencing (snRNA-seq) data from 67,988 cells of 25 MIBC tissues and single-cell RNA sequencing (scRNA-seq) data from MIBC patient-derived organoids to characterize the molecular features of bladder cancer cells co-expressing IGF2BP3 and SPHK1. Spatial transcriptomics (ST) and co-detection by indexing (CODEX) analysis were used to describe the spatial distribution and interactions of IGF2BP3 + SPHK1 + bladder cancer cells and immune cells.ResultsA subset of CD274 + ALDH + CSC-like cells was identified, associating with immunosuppression and low survival rates in MIBC patients. IGF2BP3, an m6A reader gene, was found to be upregulated in the CD274 + ALDH + CSC-like cell population and linked to poor clinical prognosis in MIBC. Knockout of IGF2BP3 dramatically promoted cell apoptosis and reduced cell proliferation in T24 cells. By integrating MeRIP-seq and bulk RNA-seq analyses, we identified SPHK1 served as a substrate for IGF2BP3 in an m6A-dependent manner. Further snRNA-seq, scRNA-seq, ST, and CODEX analysis revealed a closer topographical distance between IGF2BP3 + SPHK1 + bladder cancer cells and exhausted CD8 + T cells, providing one explanation for the superior response to immunotherapy in IGF2BP3 + SPHK1 + bladder cancer cells-enriched patients. Finally, an ICI-associated signature was developed based on the enriched genes of IGF2BP3 + SPHK1 + bladder cancer cells, and its potential ability to predict the response to immunotherapy was validated in two independent immunotherapy cohort.ConclusionsOur study highlighted the critical involvement of the IGF2BP3/SPHK1 signaling in maintaining the stemness of CSCs and promoting MIBC progression. Additionally, these findings suggested that the IGF2BP3/SPHK1 signaling might serve as a biomarker for prognosis and immunotherapy response in MIBC.

Tri-Lineage Differentiation Potential of Stem Cells from Human Exfoliated Deciduous Teeth - An In-Vitro Study

ABSTRACT Background: The use of SHED might bring advantages for tissue engineering over the use of stem cells from adult human teeth as SHEDs were reported to have higher proliferation rate and increase cell population doublings as compared with stem cells from permanent teeth. Objective: The study’s objective was to assess the growth kinetics and tri-lineage differentiation capacity of stem cells derived from human exfoliated deciduous teeth. Material and Method: After being propagated through multiple sequential subcultures, adherent fibroblastic cells in the pulp tissue culture from human exfoliation teeth were evaluated to assess their tripotent differentiation potential into bone, cartilage, and adipose cell lineages. Result: The stem cells derived from dental pulp had a comparatively high ability for proliferation and successfully differentiated into chondrocytes and osteocytes while less significant for adipocytes. Conclusion: Stem cells from Human Exfoliated Deciduous teeth are mesenchymal stem cells which are multipotent and can serve as a promising incentive for therapeutic and future research purposes.

An in-silico approach to the dynamics of proliferation potential in stem cells and the study of different therapies in cases of ovarian dysfunction

A discrete mathematical model based on ordinary differential equations and the associated continuous model formed by a partial differential equation, which simulate the generational and temporal evolution of a stem cell population, are proposed. The model parameters are the maximum proliferation potential and the rates of mitosis, death events and telomerase activity. The mean proliferation potential at each point in time is suggested as an indicator of population aging. The model is applied on hematopoietic stem cells (HSCs), with different telomerase activity rates, in a range of variation of maximum proliferation potential in healthy individuals, to study the temporal evolution of aging. HSCs express telomerase, however not at levels that are sufficient for maintaining constant telomere length with aging [1,2]. Women with primary ovarian insufficiency (POI) are known to have low telomerase activity in granulosa cells and peripheral blood mononuclear cells [3]. Extrapolating this to hematopoietic stem cells, the mathematical model shows the differences in proliferation potential of the cell populations when telomerase expression is activated using sexual steroids, though the endogenous promoter or with gene therapy using exogenous, stronger promoters within the adeno-associated virus. In the first case, proliferation potential of cells from POI condition increases, but when adeno-associated viruses are used, the proliferation potential reaches the levels of healthy cell populations.

Mitochondrial-Derived Signaling Mediates Differentiation of Parietal Epithelial Cells into Podocytes.

Aims: Parietal epithelial cells (PECs) are potential stem cells within the glomerulus, migrating into site of podocyte loss to differentiate into podocytes. Little is known about the mechanism mediating differentiation of PECs into podocytes. Results: In vitro differentiation of PECs into podocytes led to upregulation of podocyte markers such as Wilms' tumor gene 1 (WT-1), Forkhead box C1 (FOXC1), synaptopodin and podocin, accompanied by increased mitochondrial abundance. Preincubation with a mitochondrial reactive oxygen species (ROS) inhibitor prevented all these events in PECs. In vivo, adriamycin (ADR)-treated mice exhibited albuminuria, decreased WT1 positive cells, and claudin-1 expressed in glomerular capillary tuft, as well as peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) overproduction in PECs. Expression of the ROS-related molecule nuclear factor erythroid 2-related factor 2 (Nrf2) and its target protein Brahma-related gene 1 (Brg1) increased during differentiation of PECs into podocytes. Suppressing Nrf2 or Brg1 reduced the differentiation of PECs, whereas overexpression had the opposite effect. Brg1 directly regulated WT-1 transcription in PECs. Activation of Nrf2 with bardoxolone-methyl (CDDO-Me) resulted in less proteinuria and more WT1 positive cells in ADR mice. PECs conditional human Nrf2 knock-in mice showed increased WT1 cell numbers. Conclusion: It concluded that mitochondria-derived ROS mediated differentiation of PECs into podocytes via Nrf2 and Brg1 signaling.

Administration of low intensity vibration and a RANKL inhibitor, alone or in combination, reduces bone loss after spinal cord injury-induced immobilization in rats

We previously reported an ability of low-intensity vibration (LIV) to improve selected biomarkers of bone turnover and gene expression and reduce osteoclastogenesis but lacking of evident bone accrual. In this study, we demonstrate that a prolonged course of LIV that initiated at 2 weeks post-injury and continued for 8 weeks can protect against bone loss after SCI in rats. LIV stimulates bone formation and improves osteoblast differentiation potential of bone marrow stromal stem cells while inhibiting osteoclast differentiation potential of marrow hematopoietic progenitors to reduce bone resorption. We further demonstrate that the combination of LIV and RANKL antibody reduces SCI-related bone loss more than each intervention alone. Our findings that LIV is efficacious in maintaining sublesional bone mass suggests that such physical-based intervention approach would be a noninvasive, simple, inexpensive and practical intervention to treat bone loss after SCI. Because the combined administration of LIV and RANKL inhibition better preserved sublesional bone after SCI than either intervention alone, this work provides the impetus for the development of future clinical protocols based on the potential greater therapeutic efficacy of combining non-pharmacological (e.g., LIV) and pharmacological (e.g., RANKL inhibitor or other agents) approaches to treat osteoporosis after SCI or other conditions associated with severe immobilization.

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.

Advancements and mechanisms of stem cell-based therapies for spinal cord injury in animals.

Spinal cord injury (SCI) is a neurodegenerative disorder of the central nervous system (CNS) that can lead to permanent loss of sensation and voluntary movement beyond the affected area. Extensive preclinical and clinical trials have been conducted to evaluate the safety and effectiveness of stem cells for the treatment of various CNS diseases or disorders, including SCI. However, several challenges hinder nerve cell regeneration in the injured spinal cord, such as extensive cell loss, limited neural cell regeneration capacity, axonal disruption, and the presence of growth-inhibiting molecules, particularly astroglial scarring or glial scars at the injury site in chronic cases. These obstacles pose significant challenges for physicians in restoring normal motor and sensory nerve function in both humans and animals following SCI. This review focuses on SCI pathogenesis, the mechanisms underlying the therapeutic potential of Mesenchymal Stem Cells (MSCs) in SCI, and the potential of stem cell-based therapies as promising avenues for treatment. This review article also included relevant preclinical and clinical data from animal studies.

Hierarchically structured nanofibrous scaffolds spatiotemporally mediate the osteoimmune micro-environment and promote osteogenesis for periodontitis-related alveolar bone regeneration

Periodontitis suffer from inflammation-induced destruction of periodontal tissues, resulting in the serious loss of alveolar bone. Controlling inflammation and promoting bone regeneration are two crucial aspects for periodontitis-related alveolar bone defect treatment. Herein, we developed a hierarchically structured nanofibrous scaffold with a nano-embossed sheath and a bone morphogenetic protein 2-loaded core to match the periodontitis-specific features that spatiotemporally modulated the osteoimmune environment and promoted periodontal bone regeneration. We investigated the potential of this unique scaffold to treat periodontitis-related alveolar bone defects in vivo and in vitro. The results demonstrated that the hierarchically structured scaffold effectively reduced the inflammatory levels in macrophages and enhanced the osteogenic potential of bone mesenchymal stem cells in an inflammatory microenvironment. Moreover, in vivo experiments revealed that the hierarchically structured scaffold significantly ameliorated inflammation in the periodontium and inhibited alveolar bone resorption. Notably, the hierarchically structured scaffold also exhibited a prolonged effect on promoting alveolar bone regeneration. These findings highlight the significant therapeutic potential of hierarchically structured nanofibrous scaffolds for the treatment of periodontitis, and their promising role in the field of periodontal tissue regeneration. Statement of Significance: We present a novel hierarchically structured nanofibrous scaffold of coupling topological and biomolecular signals for precise spatiotemporal modulation of the osteoimmune micro-environment. Specifically, the scaffold was engineered via coaxial electrospinning of the poly(ε-caprolactone) sheath and a BMP-2/polyvinyl alcohol core, followed by surface-directed epitaxial crystallization to generate cyclic nano-lamellar embossment on the sheath. With this unique hierarchical structure, the cyclic nano-lamellar sheath provided a direct nano-topographical cue to alleviate the osteoimmune environment, and the stepwise release of BMP-2 from the core provided a biological cue for bone regeneration. This research underscores the potential of hierarchically structured nanofibrous scaffolds as a promising therapeutic approach for periodontal tissue regeneration and highlights their role in advancing periodontal tissue engineering.

Mesenchymal stem cell transplant as an intervention to ameliorate disuse-induced muscle atrophy in a mouse model of simulated microgravity

BackgroundThe hindlimb unloaded (HU) mouse model exhibits disuse-induced muscle atrophy. However, effective interventions remain elusive. We investigated the therapeutic potential of mesenchymal stem cells (MSC) transplant on muscle decline in HU mice. MethodsWe divided 4-month-old male c57BL/6j mice into controls and HU mice treated with PBS as placebo (HU-PBS) or MSCs (HU-MSC; one million cells/100 μl PBS into gastrocnemius muscles once a week) for three weeks. We measured muscle mass, grip strength, and an unbiased transcriptome analysis of gastrocnemius muscles. ResultsMSC treatment prevented muscle atrophy and improved grip strength in HU mice. Transcriptome analysis revealed MSC-induced unique (557 genes) and differential (1,214 genes) expressions of several genes compared to the HU-PBS group. GO and KEGG term analysis revealed an HU-induced downregulation of pathways associated with the regulation of contractile apparatus, neuromuscular junction, and satellite cell function, which were partly reversed with MSC treatment. Lastly, MSC treatment also upregulated the pathways controlling muscle differentiation and growth in the HU mice. ConclusionAltogether, we report the therapeutic potential of MSCs in treating disuse-induced muscle atrophy and weakness. Our study may help unravel novel molecular mechanisms involved in MSCs-induced muscle restoration.

Influence of budesonide and fluticasone propionate in the anti-osteoporotic potential in human bone marrow-derived mesenchymal stem cells via stimulation of osteogenic differentiation

Osteoporosis is a prevalent bone condition with adverse effects observed in patients undergoing long-term glucocorticoid therapy, resulting in bone demineralization and tissue loss. There has been limited studies on the global response to dexamethasone in terms of comparing its expression profile to other common glucocorticoids during osteogenic differentiation. This study focused on the downregulated gene expression profile of glucocorticoid compounds; dexamethasone, budesonide, and fluticasone propionate, during osteogenic differentiation to elucidate the related target genes and pathways associated with the anti-osteoporotic potential of telomerase-immortalized human bone marrow-derived mesenchymal stem cells using a bioinformatics approach. Based on gene expression microarrays experiments and bioinformatics analysis, several key genes involved in the regulation of osteogenic differentiation and osteoporosis development in mesenchymal stem cells that were targeted by these specific glucocorticoids were determined. Network analysis using GeneCards, OMIM, and CTD databases were performed and osteoporosis-related genes were identified. LIMMA and moderated Welch test R packages were performed to determine significant downregulated differentially expressed genes for each glucocorticoid treatment. A total of 479 (dexamethasone), 84 (budesonide), and 889 (fluticasone propionate) differentially expressed genes were identified for each glucocorticoid, of which 35 common genes overlapped. Enrichment pathway analysis was conducted using Metascape, and protein-protein interaction networks were constructed using the STRING database and Cytoscape software to determine potential target genes involved with osteoporosis. Enrichment pathway analysis revealed genes involved in 3 Reactome pathways namely cytokine signaling in immune system, immune system and the interferon alpha/beta signaling pathways and identified 10 hub genes based on the PPI network to determine potential target pathways associated with osteoporosis. These findings provide preliminary insights into the relationship between the key target genes of dexamethasone, budesonide, and fluticasone propionate, and the pathways associated with regulated osteoporosis metabolism during osteogenic differentiation.

Adipose-derived Stem Cells for Treatment of Diabetic Foot Ulcers: A Review

Abstract: This study investigates the therapeutic potential of adipose-derived stem cells (ASCs) in diabetic foot ulcers (DFUs). The goal is to further research regenerative medicine by improving knowledge of ASC-based therapies in diabetic wound management. A comprehensive literature review included studies from reputable databases, including PubMed and the Cochrane Library. We paid particular attention to the clinical, in vivo, and in vitro investigations of the utility and effectiveness of ASCs in treating DFU. We also highlighted novel isolation techniques and application methods for ASCs in chronic wound management. ASCs have shown great potential in regenerative interventions for diabetes, especially in DFU management. These cells facilitate wound repair by differentiating into different cell types, promoting angiogenesis, secreting growth factors, reducing inflammation, and increasing wound perfusion. However, the current body of research on ASC applications for DFU still requires further investigation. This shows the importance of thoroughly studying their biological mechanisms and therapeutic uses. This review establishes that ASC-based treatments effectively enhance outcomes for patients suffering from DFU. We recommend further investigation of the functionality of ASCs and therapeutic approaches to maximize their therapeutic potential in managing diabetic wounds, thereby advancing the development of regenerative medicine.