Search Results (726)

Neuroinflammation is a key feature of Alzheimer’s disease (AD), and stem cell therapies have emerged as promising candidates due to their immunomodulatory properties. Neuro-Cells (NC), a combination of unmodified mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs), have demonstrated therapeutic potential in models of central nervous system (CNS) injury and neurodegeneration. Here, we studied the effects of NC in APPswe/PS1dE9 mice, an AD mouse model. Twelve-month-old APPswe/PS1dE9 mice or their wild-type littermates were injected with NC or vehicle into the cisterna magna. Five to six weeks post-injection, cognitive, locomotor, and emotional behaviors were assessed. The brain was stained for amyloid plaque density using Congo red, and for astrogliosis using DAPI and GFAP staining. Gene expression of immune activation markers (Il-1β, Il-6, Cd45, Tnf) and plasticity markers (Tubβ3, Bace1, Trem2, Stat3) was examined in the prefrontal cortex. IL-6 secretion was measured in cultured human monocytes following endotoxin challenge and NC treatment. Untreated APPswe/PS1dE9 mice displayed impaired learning in the conditioned taste aversion test, reduced object exploration, and anxiety-like behavior, which were improved in the NC-treated mutants. NC treatment normalized the expression of several immune and plasticity markers and reduced the density of GFAP-positive cells in the hippocampus and thalamus. NC treatment decreased amyloid plaque density in the hippocampus and thalamus, targeting plaques of <100 μm². Additionally, NC treatment suppressed IL-6 secretion by human monocytes. Thus, NC treatment alleviated behavioral deficits and reduced amyloid plaque formation in APPswe/PS1dE9 mice, likely via anti-inflammatory mechanisms. The reduction in IL-6 production in human monocytes further supports the potential of NC therapy for the treatment of AD. Full article

Background/Objectives: Chronic wounds represent a significant clinical and public health challenge due to impaired tissue repair and high associated morbidity. This study investigates the therapeutic potential of the secretome derived from human mesenchymal stem cells obtained from the pulp of deciduous teeth (hDP-MSCs) in promoting skin wound healing. Methods: After confirming the mesenchymal identity and multipotent differentiation potential of hDP-MSCs by using flow cytometry and histological staining, the effects of the secretome on human keratinocyte (HaCaT) cultures were evaluated. Results: Scratch assays, performed under high- and low-glucose conditions, demonstrated that the secretome significantly promoted keratinocyte migration and wound closure without compromising cell viability. Additionally, the secretome modulated the expression of key genes involved in inflammation and tissue regeneration, including IL-1β, TNF-α, TGF-β1, and VEGF-α, in a time-dependent manner. Under inflammatory conditions induced by lipopolysaccharide, co-treatment with the secretome significantly reduced TNF-α expression and increased TGF-β1 expression, suggesting an anti-inflammatory effect. Conclusions: These findings indicate the potential of the hDP-MSC-derived secretome as a promising cell-free therapeutic strategy capable of accelerating skin regeneration and modulating the inflammatory response during the wound healing process. Full article

An investigation into the biological mechanisms initiated in wounded skin following the application of mesenchymal stem cells (MSCs) and nanoparticles (NPs) (Ag, ZnO), either alone or combined, was performed in mice, with the aim of determining the optimal approach to accelerate the healing process. This combined treatment was hypothesized to be beneficial, as it is associated with the production of molecules supporting the healing process and antimicrobial activity. The samples were collected seven days after injury. When compared with untreated wounded animals (controls), the combined (MSCs+NPs) treatment induced the expression of Sprr2b, encoding small proline-rich protein 2B, which is involved in keratinocyte differentiation, the response to tissue injury, and inflammation. Pathways associated with keratinocyte differentiation were also affected. Ag NP treatment (alone or combined) modulated DNA methylation changes in genes involved in desmosome organization. The percentage of activated regulatory macrophages at the wound site was increased by MSC-alone and Ag-alone treatments, while the production of nitric oxide, an inflammatory marker, by stimulated macrophages was decreased by both MSC/Ag-alone and MSCs+Ag treatments. Ag induced the expression of Col1, encoding collagen-1, at the injury site. The results of the MSC and NP treatment of skin wounds (alone or combined) suggest an induction of processes accelerating the proliferative phase of healing. Thus, MSC-NP interactions are a key factor affecting global mRNA expression changes in the wound. Full article

Stem cells cultured in cell aggregates exhibit higher cell survival rates and enhanced anti-inflammatory and angiogenic effects compared to single cells, constructing a stable and economical cell aggregate culture system that can accurately adjust the mass transfer distance of nutrients, which contributes to improving the therapeutic effects of stem cell aggregates. In this study, an alginate hydrogel microsphere culture system (Alg-HM) was prepared using electrostatic spraying technology and refined by optimizing the electrostatic spraying technology parameters, such as the sodium alginate concentration, voltage, electrospray injection speed, and nozzle inner diameter. Furthermore, by setting the Tip-dropped culture system (Tip-D culture system, created by dropping the resuspended hMSC aggregate–hydrogel solution with a tip to form the hydrogel microsphere) and Matrigel culture system (created by dropping the resuspended hMSC aggregates–Matrigel solution with a tip to form the Matrigel culture system) as the control group and Alg-HM as the experimental group, the culture effect of hMSC aggregates in the optimized Alg-HM culture system was tested; CCK-8 detection and Ki-67 immunofluorescence staining showed that the Alg-HM culture system significantly enhanced the cell proliferation activity of hMSC aggregates after 7 and 14 days of culture. The Calcein-AM/PI cell staining results showed that the Alg-HM culture system can significantly reduce the central necrosis of hMSC aggregates. The RNA sequencing results showed that the Alg-HM culture system can significantly activate the signaling pathways related to cell proliferation in hMSCs. This culture system is helpful for the culture of cell aggregates in vitro and efficient transplantation in vivo. Full article

A varied family of polyphenolic chemicals, flavonoids, are becoming more and more important in bone tissue engineering because of their osteogenic, anti-inflammatory, and antioxidant effects. Recent developments incorporating flavonoids into different biomaterial platforms to improve bone regeneration are emphasized in this study. Osteocalcin (OCN) expression was 2.1-fold greater in scaffolds loaded with flavonoids—such as those made of polycaprolactone (PCL)—greatly increasing human mesenchymal stem cell (hMSC) proliferation and mineralization. Comparably, a threefold increase in calcium deposition indicates increased mineralization when hydroxyapatite (HA) was functionalized with flavonoids such as quercetin. These HA scaffolds with flavonoids also showed a 45% decrease in osteoclast activity, therefore promoting balanced bone remodeling. Concurrent with flavonoids like EGCG and quercetin, chitosan-based scaffolds encouraged osteogenic differentiation with increases in osteogenic markers like osteopontin (OPN) and alkaline phosphatase (ALP) expression by up to 82%. These scaffolds also showed 82% bone defect repair after six weeks in vivo, suggesting their promise in rapid bone regeneration. With an increase of up to 32% in the bone volume-to-total volume ratio (BV/TV) and 28% greater bone–implant contact (BIC), flavonoid coatings on titanium implants enhanced osteointegration in implantology. Displaying successful osteogenesis and immunomodulation, the addition of flavonoids into metal–organic frameworks (MOFs) and injectable hydrogels demonstrated a 72% increase in new bone formation in vivo. Though further research is required to confirm long-term clinical effectiveness, these findings show the great promise of flavonoid-functionalized biomaterials in bone regeneration. Full article

Cell technologies have provided promising tools for modulating the properties of multipotent mesenchymal stem/stromal cells (MSCs) to meet the needs of cell therapy as well as tissue engineering and regenerative medicine (TERM). Ex vivo preconditioning is directed at enhancing the engraftment of MSCs and activating their secretory activity, primarily the production of soluble mediators. The present review aims to highlight the underestimated effect of the most accepted preconditioning approaches on the modification of the important set of insoluble molecules secreted by MSCs into extracellular space—the extracellular matrix (ECM). A thorough review of the published literature was performed, with particular emphasis on ECM-related data. The analysis of data on ECM changes showed that most of the applied preconditioning methods—hypoxia, inflammatory priming, pharmacological agents, 3D culture, and scaffolds—generally stimulate ECM production, increase the deposition of growth factors, promote alignment, and increase ECM stiffness. There are already preliminary results demonstrating the successful application of preconditioned ECM for promoting angiogenesis, targeted stromal lineage differentiation, and other therapeutic goals. The prospects for further research in this area are discussed. Full article

Mesenchymal stem cells (MSCs) have recently shown great promise as potential anticancer drug delivery carriers. MSCs exhibit tropism to inflammatory sites, such as tumor beds, and resistance to chemotherapeutics. The aim of this study was to examine the efficacy of gemcitabine (GEM) conjugated with flurbiprofen (FLU) as a potential agent enhancing the GEM cytotoxic effect. Pancreatic cancer cell lines (PCCs), including PANC-1, AsPC-1, and BxPC-3, were studied meticulously. Moreover, the usefulness of bone-marrow-derived mesenchymal stem cells (BM-MSCs) treated with GEM and FLU, and the conditioned media from above these cells (CM) as elements supporting the in vitro action of GEM, inducing apoptosis, necrosis, and inhibiting the cell cycle, was tested. The results showed that CM-GEM exhibited higher cytotoxicity towards the selected PCCs compared to GEM alone. Furthermore, the obtained data revealed lower sensitivity of these cells to treatment, which promotes the utilization of BM-MSCs as potential drug carriers. Based on the presented findings, it seems that applying FLU in the antiproliferative effect of GEM might be regarded as an effective strategy in the therapy of pancreatic cancer, especially in the inhibition of proliferation and induction of cancer cell death. Full article

Plantar fasciitis is a common condition characterized by inflammation and degeneration of the plantar fascia, leading to heel pain and reduced mobility. Affecting both athletic and non-athletic populations, it is a leading cause of foot-related medical visits. Conservative treatments, including rest, physical therapy, and corticosteroid injections, provide relief for most patients, but a subset experiences persistent symptoms requiring advanced therapies. Emerging biologic treatments, such as platelet-rich plasma (PRP) and mesenchymal stem/stromal cell (MSC) therapy, have demonstrated potential in promoting tissue regeneration and reducing inflammation. Recently, MSC-derived extracellular vesicles (MSC-EVs) have gained attention for their regenerative properties, offering a promising, cell-free therapeutic approach. EVs mediate tissue repair through immunomodulation, anti-inflammatory signaling, and extracellular matrix stabilization. Preclinical studies suggest that EV therapy may improve tendon and ligament healing by promoting M2 macrophage polarization, inhibiting excessive metalloproteinase activity, and enhancing vascular remodeling. This review explores the potential of MSC-EVs as an innovative, non-surgical treatment for plantar fasciitis, addressing their mechanisms of action and current evidence in musculoskeletal regeneration. Full article

Background/Objectives: Mesenchymal stem cells (MSCs) possess immunomodulatory properties, tumor-homing, and low immunogenicity, making them attractive for cell-based cancer therapies, but their role in colorectal cancer (CRC) remains controversial. The MSC1 phenotype, a pro-inflammatory, tumor-suppressive state induced by short-term, low-dose LPS activation via TLR4, has shown therapeutic promise but remains poorly characterized in CRC. We aimed to elucidate MSC1’s tumor-suppressive mechanisms and validate its activity against CRC cells using an integrated bioinformatics and in vitro approach. Methods: We constructed a high-confidence protein-protein interaction (PPI) network in Wharton’s jelly-derived MSCs (WJ-MSCs) following TLR4 activation to uncover enriched signaling pathways, transcriptional regulators, and secreted factors. Functional and transcriptional enrichment analyses pinpointed key mechanisms. We then co-cultured MSC1 cells with CRC cells to assess effects on proliferation and metabolism. Results: Network analysis revealed six tumor-suppressive mechanisms of MSC1 cells: (i) Metabolic reprogramming via enhanced glucose and lipid uptake, phosphoinositide signaling, and membrane/protein recycling, (ii) Robust antioxidant defenses, including SOS signaling and system xc⁻, (iii) Extracellular matrix stabilization and laminin-111–integrin-mediated adhesion, (iv) Secretome with direct anti-cancer effects, (v) Regulation of survival and cancer-associated fibroblasts (CAFs) formation inhibition through balanced proliferation, apoptosis, and epigenetic signals, (vi) Controlled pro-inflammatory signaling with anti-inflammatory feedback. In vitro, MSC1 cells significantly suppressed CRC cell proliferation and metabolic activity versus controls. Conclusions: This study provides the first mechanistic map of MSC1’s tumor-suppressive functions in CRC, extending beyond immunomodulation to include metabolic competition, ECM stabilization, and anti-cancer secretome activity. These findings establish MSC1 cells as a novel therapeutic strategy for CRC in cell-based cancer therapies. Full article

Inflammatory arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA), is a group of degenerative joint diseases that result in reduced mobility and a prevalent cause of disability. Despite differing etiologies, both conditions involve inflammation, affecting only the joints in OA and systemic in RA due to its autoimmune nature. Regenerative medicine offers promising alternatives, with a focus on the therapy with mesenchymal stem cell (MSC) and their secreted extracellular vesicles (EVs). MSC-derived EVs have shown great potential in modulating inflammatory pathways and promoting tissue repair in the preclinical models of RA and OA. Additionally, EVs from immune cells exhibit strong anti-inflammatory effects, reducing cartilage and bone degeneration. This review highlights the recent progress in MSC-based and EV-based therapies for OA and RA, discussing the bioengineering approaches that enhance the therapeutic efficacy, stability, and targeting of EV. It also addresses the major challenges in translating EV therapy from the laboratory to clinical practice and discusses strategies to overcome these obstacles in the treatment of inflammatory arthritis. Full article

Osteoarthritis (OA) is a debilitating joint disorder characterized by cartilage degradation, inflammation, and loss of joint function. While mesenchymal stem cells (MSCs) hold promise for OA therapy due to their regenerative and immunomodulatory properties, challenges such as poor survival, suboptimal differentiation, and an inflammatory microenvironment limit their clinical efficacy. Natural products, including curcumin, resveratrol, quercetin, and epigallocatechin gallate (EGCG), have emerged as a complementary strategy to enhance MSC-based therapies for OA. These bioactive compounds modulate key inflammatory pathways (NF-κB, MAPK, PI3K/AKT), reduce oxidative stress, and promote chondrogenic differentiation of MSCs. Preclinical studies demonstrate the synergistic effects of MSCs and natural products in attenuating inflammation, enhancing cartilage repair, and improving joint function in OA models. However, clinical translation is hindered by challenges in bioavailability, standardization of MSC protocols, and regulatory hurdles. Future research should focus on optimizing delivery systems, conducting large-scale randomized controlled trials, and establishing personalized treatment strategies based on patient biomarkers. By addressing these challenges, the integration of natural products into MSC-based therapies could revolutionize OA treatment, offering a disease-modifying approach for millions of patients worldwide. Full article

Osteoarthritis (OA) is a prevalent and debilitating joint disorder that affects a substantial proportion of the global population, underscoring the urgent need for therapeutic strategies that extend beyond symptomatic management. Although mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality, their clinical application remains constrained by several inherent limitations. This study explores a cell-free alternative by investigating the therapeutic potential of exosomes derived from bone marrow (BMSCs), adipose tissue (ADSCs), and umbilical cord (UMSCs) MSCs in mitigating OA pathogenesis, utilizing both in vitro and ex vivo models. Exosomes from each MSC source were isolated and characterized through nanoparticle tracking analysis, transmission electron microscopy, and Western blotting to confirm their identity and purity. Subsequently, their chondroprotective, anti-inflammatory, and regenerative properties were systematically assessed through evaluations of cell viability, expression profiles of inflammatory and chondroprotective markers, and chondrocyte migration assays. The results demonstrate that all three types of MSC-derived exosomes (MSC-Exos) exhibit low cytotoxicity while significantly suppressing proinflammatory markers and enhancing the expression of chondroprotective genes. Notably, BMSC-Exos and UMSC-Exos displayed superior efficacy in attenuating inflammation, promoting cartilage protection, and inhibiting chondrocyte apoptosis. Furthermore, all MSC-Exos markedly enhanced chondrocyte motility, a critical component of cartilage repair. Collectively, these findings support the therapeutic promise of MSC-Exos, particularly those derived from BMSCs and UMSCs, as a targeted, cell-free approach for the treatment of OA compared to ADSCs. By modulating inflammation, promoting cartilage regeneration, and preventing chondrocyte apoptosis, MSC-Exos may serve as a viable and scalable alternative to current MSC-based therapies for this widespread degenerative disease. Full article

Prion diseases are disorders caused by the misfolding of prion protein (PrP^Sc), leading to the accumulation of an abnormal form of the normal prion protein (PrP) found in the host. The secretome of mesenchymal stem cells (MSCs), including paracrine-soluble factors, holds promising potential to stimulate host regenerative capability and alleviate organ disorders. In this research, our goal was to investigate the neuroprotective properties of the secretome derived from adipose-derived mesenchymal stem cells (AdMSC secretome) in relation to the toxicity caused by PrP^106−126 in SH-SY5Y cells. The findings showed that PrP^106−126 treatment exacerbated the neurotoxicity of SH-SY5Y cells, as indicated by increased lactate dehydrogenase (LDH) release. However, the AdMSC secretome significantly decreased LDH release. Under PrP^106−126 stimulation, the AdMSC secretome downregulated inflammatory markers (TNF-α and IL-1β) and upregulated anti-inflammatory IL-10. Treatment with the AdMSC secretome markedly reduced GFAP immunoreactivity in astrocytic C8D1A cells compared to treatment with PrP^106−126 alone. In addition, the AdMSC secretome reduced Iba-1 immunoreactivity in BV2 cells activated by LPS. Western blot analysis showed that the AdMSC secretome inhibited pro-apoptotic factor Bax induced by PrP^106−126 and increased the expression of anti-apoptotic factor Bcl-2. However, no significant difference was observed in the expression of caspase-3. The AdMSC secretome exhibited a considerable migratory effect on SH-SY5Y cells after 24 h, as demonstrated by the scratch assay. The results suggest that the AdMSC secretome can attenuate PrP^106−126-induced neuronal damage. Full article

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality despite advances in medical and interventional therapies. Mesenchymal stem cell (MSC) therapy has emerged as a promising regenerative approach for patients with refractory or non-revascularizable CAD. MSCs exhibit unique immunomodulatory, pro-angiogenic, and anti-fibrotic properties, primarily through paracrine mechanisms involving the secretion of cytokines, growth factors, and exosomal microRNAs. Clinical and preclinical studies have demonstrated improvements in myocardial perfusion, left ventricular ejection fraction (LVEF), and functional capacity following MSC-based interventions, particularly in patients with low baseline LVEF and heightened inflammation. Various MSC sources—including bone marrow, adipose tissue, and umbilical cord—offer distinct advantages, while delivery strategies such as intracoronary, intramyocardial, intravenous, and subcutaneous administration impact cell retention and efficacy. Advances in genetic modification, hypoxic preconditioning, and exosome-based therapies aim to enhance MSC survival and therapeutic potency. However, challenges persist regarding cell engraftment, cryopreservation effects, and inter-patient variability. Moving toward precision cell therapy, future approaches may involve stratifying patients by inflammatory status, ischemic burden, and comorbidities to optimize treatment outcomes. MSCs may not yet replace conventional therapies but are increasingly positioned to complement them within a personalized, regenerative framework for CAD management. Full article

Diabetic foot ulcers (DFU) represent a major complication of diabetes mellitus, affecting millions of patients worldwide and leading to high morbidity and amputation risks. The impaired healing process in DFU is driven by vascular insufficiency, neuropathy, chronic inflammation, and infections. Conventional treatments, including blood sugar control, wound debridement, and standard dressings, have shown limited efficacy in achieving complete healing. Recent advancements have introduced novel therapeutic approaches such as stem cell therapy, exosome-based treatments, and bioengineered scaffolds to accelerate wound healing and tissue regeneration. Mesenchymal stem cells (MSCs), particularly adipose-derived stem cells (ASCs), exhibit anti-inflammatory, pro-angiogenic, and immunomodulatory properties, enhancing wound repair. Additionally, exosomes derived from ASCs have demonstrated the ability to promote fibroblast proliferation, regulate inflammation, and stimulate angiogenesis. The integration of bioengineered scaffolds, including hydrogels, hyaluronic acid (HA), or micro-fragmented adipose tissue (MFAT), offers improved drug delivery mechanisms and a controlled healing environment. These scaffolds have been successfully utilized to deliver stem cells, growth factors, antioxidants, anti-glycation end products, anti-inflammatory and anti-diabetic drugs, or antimicrobial agents, further improving DFU outcomes. This review highlights the potential of combining novel 3D scaffolds with anti-diabetic drugs to enhance DFU treatment, reduce amputation rates, and improve patients’ quality of life. While promising, further clinical research is required to validate these emerging therapies and optimize their clinical application. Full article