Adipose-derived Mesenchymal Stem Cells Research Articles (Page 1)

Metastasis is the primary cause of death in advanced/recurrent cancer patients. Cancer metastatic capability depends not only on cancer cells but also on the cancer microenvironment, particularly cancer-associated fibroblasts (CAFs), a highly heterogeneous population. Our prior work identified a POSTN-secreting CAFs subpopulation linked to gastric cancer (GC) invasion and poor survival. The Cancer Genome Atlas analysis in GC showed POSTN association with epithelial-mesenchymal transition and extracellular matrix degradation pathways. In vitro, GC exosomes induced adipose-derived mesenchymal stem cells (MSCs) into POSTN-expressing CAFs. Lentiviral POSTN overexpression in CAFs enhanced GC cell migration/invasion, while knockdown had the opposite effect. These results were validated in a nude mouse GC model. As POSTN is an integrin ligand, POSTN-positive CAFs (POSTN+ CAFs) activated integrin downstream AKT signaling. AKT inhibition significantly diminished the pro-migratory/invasive effect of POSTN-overexpressing CAFs. In summary, POSTN+ CAFs promote GC invasion via AKT pathway activation.

Cavernous nerve injury (CNI) is a prominent etiological factor in the development of erectile dysfunction (ED). Nevertheless, the underlying pathophysiological mechanisms of CNI-induced ED (CNI-ED) are not fully elucidated. Galectin-3 (Gal-3), an indicator of inflammation and fibrosis, has been implicated in the pathogenesis of arteriogenic ED. In this study, we investigate the role of Gal-3 in CNI-ED and explore the potential mechanisms by which adipose-derived mesenchymal stem cell exosomes (ADSC-Exo) ameliorate CNI-ED. We established a bilateral CNI (BCNI) rat model and evaluated erectile function using intracavernous pressure (ICP), mean arterial pressure (MAP), and infrared ray thermography (IRT). The expression level of Gal-3 was measured in the major pelvic ganglia (MPG), penile corpus cavernosum, and cultured cells, with its expression modulated by lentiviral vectors. A combination of experimental approaches, including western blot, immunofluorescence, and flow cytometry analysis, were employed to investigate the role of Gal-3 in the progression of CNI-ED. Additionally, the potential molecular mechanisms by which ADSC-Exo ameliorates CNI-ED were explored. Our findings indicated that the expression of Gal-3 is significantly upregulated in the MPG and penile corpus cavernosum of BCNI rats. This upregulation was accompanied by oxidative stress and activation of the TLR4/MyD88/NF-κB signaling pathway. Following lentiviral knockdown of Gal-3, erectile function in BCNI rats was improved. Moreover, ADSC-Exo transplantation inhibited Gal-3 expression and the related inflammatory profibrotic cascades. Collectively, this study demonstrates that upregulation of Gal-3 promotes the pathogenesis of CNI-ED by triggering oxidative stress and inflammatory profibrotic cascades and highlights the therapeutic potential of ADSC-Exo in restoring erectile function via Gal-3 inhibition.

Osteonecrosis of the femoral head (ONFH), driven by glucocorticoid-induced M1 macrophage polarization and disrupted inflammatory homeostasis, poses a critical challenge in orthopedics. Here, we engineered adipose-derived mesenchymal stem cell exosomes (ADMSC-Exos) via metabolic glycoengineering (MGE) to deliver α2-macroglobulin (A2M), generating DS-exo@A2M. This nanoconstruct synergistically suppressed M1 polarization ( ↓ TNF-α, ↓IL-6) and promoted M2 polarization (↑CD206, ↑Arg-1) in M1 macrophages through IL-4 signaling activation, evidenced by transcriptomic/proteomic profiling and shRNA-mediated IL-4 knockdown. DS-exo@A2M further enhanced osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) by upregulating RUNX2, ALP, and OCN. In a rat ONFH model, DS-exo@A2M restored trabecular architecture ( ↑ BV/TV, ↓Tb.Sp) and reduced bone marrow edema. Mechanistically, IL-4 silencing abolished DS-exo@A2M-mediated macrophage reprogramming and osteogenesis, confirming pathway specificity. This study establishes a precision nanotherapeutic strategy for ONFH by integrating exosome engineering, immunomodulation and biosafety assessment, offering a translational framework for treating inflammation-associated bone disorders.

Three-dimensional (3D)-printed biodegradable breast scaffolds with patient-specific shapes and tissue-specific mechanics have attracted increased attention for soft tissue reconstruction. However, it still remains a challenge for the existing porous breast scaffolds to promote adipose tissue regeneration and alleviate fibrous tissue ingrowth due to their limited immunomodulatory capabilities. Here, we propose to integrate adipose-derived mesenchymal stem cell exosome (ADSC-Exo)-laden Gelatin Methacryloy (GelMA) hydrogels with 3D-printed polycaprolactone (PCL) scaffolds (Exo@GelMA+PCL) to promote macrophage M2 polarization for enhanced adipose regeneration. Compared with physically-absorbed Exo+PCL scaffolds, the Exo@GelMA+PCL biohybrid scaffolds exhibited sustained Exo release (>80%) at day 14. As confirmed by immunofluorescence and RT-qPCR, RAW264.7 macrophages tend to polarize toward the M2 phenotype after internalizing the released Exos. Additionally, conditioned medium from Exo@GelMA+PCL biohybrid scaffold-macrophage cocultures were found to effectively boost ADSCs proliferation, migration, and adipogenic differentiation. Furthermore, the Exo@GelMA+PCL biohybrid scaffolds significantly increased M2 macrophage proportions versus controls (GelMA+PCL, PCL scaffolds) when implanted in vivo, which achieved markedly higher fat area percentages (46.26 ± 4.55%) compared to GelMA+PCL scaffolds (23.76 ± 1.90%) and PCL scaffolds (26.14 ± 2.55%). The presented biohybrid scaffolds demonstrate immunomodulatory properties that enhance soft tissue regeneration, indicating significant potential for application in breast reconstruction.

Pancreatic cancer (PC) is characterized by extensive desmoplasia, with heterogeneous cancer-associated fibroblasts (CAFs) as a major component. However, the contribution of distinct precursor cells to CAF heterogeneity remains poorly defined. This study investigated the role of Muc5ac in modulating CAF heterogeneity by maturing precursor cells, including adipose-derived mesenchymal stem cells (AD-MSCs), bone marrow-derived MSCs (BM-MSCs), and pancreatic stellate cells (PSCs), into different CAF subsets. RNA sequencing of precursor cells treated with conditioned media from Muc5ac-proficient or -deficient cancer cells revealed distinct transcriptional profiles. Muc5ac significantly increased the expression of DNMT3B and TET1 in AD-MSCs, promoting the acquisition of extracellular matrix production, cytokine signaling, and antigen-presentation programs characteristic of both inflammatory (iCAF) and myofibroblastic CAF phenotypes (myCAF). In PSCs, Muc5ac increased H3K27 acetylation independent of its interactome, which was validated in autochthonous murine models. Transcriptome analysis demonstrated that AD-MSCs contributed 44.4% to the CAF population, followed by PSCs (31.5%) and BM-MSCs (21.6%). Gene ontology and KEGG analyses revealed distinct functional programs for each precursor population contributing to CAF heterogeneity. An age-dependent signature in AD-MSC maturation was identified, with a significant positive correlation between serum INHBA and MUC5AC from younger (≤55 years, n=20) compared with older patients (≥75 years, n=20).

This study describes the green synthesis of a neodymium oxide/magnetic iron oxide (Nd2O3/Fe3O4) nanocomposite, functionalized with hydroxyapatite, using Elaeagnus angustifolia L. seeds extract. Then the effectiveness of electrospun polycaprolactone-collagen (PCL-COL) loaded with nanoparticles composites as scaffolds for bone tissue engineering was evaluated. The synthesis of nanoparticles and their elemental identification were confirmed using XRD, FT-IR, and EDX techniques. The DLS, TEM, and SEM analysis demonstrated the generation of Nd-Fe3O4@HAp NPs with an average diameter of 14-18nm. Vibrating Sample Magnetometry (VSM) validated the ferromagnetic and superparamagnetic characteristics of the nanoparticles. Tensile and contact angle analysis revealed that NP-loaded electrospun scaffolds exhibited markedly enhanced mechanical characteristics and hydrophilicity relative to pristine polymer specimens, owing to the homogeneous distribution of nanofillers throughout the polymer fibers. Additionally, cellular investigations and osteogenic potential were evaluated in vitro using adipose-derived mesenchymal stem cells (ADMSCs). Assessments of cell attachment, spreading, and proliferation of ADMSCs were conducted using SEM observation and thiazolyl blue (MTT) test. The osteogenic differentiation potential of ADMSCs on the fabricated nanofiber scaffolds was evaluated using alkaline phosphatase activity, calcium content test, and western blot analysis. ADMSCs showed better initial adherence and infiltration in nanoparticle-enhanced scaffolds compared to PCL/COL scaffolds. Additionally, our Western blot analysis demonstrated that scaffolds can effectively induce osteogenic differentiation in ADMSCs by up-regulating key proteins associated with osteogenesis (p-value < 0.0001). Thus, nanoparticle-loaded electrospun nanofibers exhibit considerable potential as effective scaffolds for applications in bone tissue engineering.

Graviola Extract versus Adipose-Derived Mesenchymal Stem Cells as Therapeutics in Repairing Liver Damage Caused by 2-Amino-3-Methylimidazo[4, 5-f]quinoline

Introduction: Adipose-derived mesenchymal stem cells (AD-MSCs) cultured under hypoxic conditions are known to secrete extracellular vesicles (EVs) with protective effects against ischemia. In this study, we aimed to evaluate the enhanced therapeutic potential of these EVs—emerging as a promising cell-free strategy for cardiac regeneration—when derived from hypoxia-conditioned AD-MSCs. Materials and Methods: MSCs were isolated from the adipose tissue of Lewis rats and cultured under normoxic (20% O2) or hypoxic (5% O2) conditions. EVs were collected from conditioned media via ultracentrifugation. EV marker protein expression assessed the quantity of EVs, and comprehensive miRNA profiling was performed. To evaluate therapeutic efficacy, myocardial infarction (MI) was induced in Lewis rats via ligation of the left anterior descending artery. Two weeks after MI, rats were divided into three groups: normoxic EVs (N-EV), hypoxic EVs (H-EV), and PBS control. Each treatment was locally injected around the infarct border zone. Four weeks later, cardiac function was assessed by echocardiography and histological analyses were conducted. Results: There was no significant difference in the amount of EVs, as assessed by Alix quantification, between the hypoxic-and normoxic groups (p = 0.25)(Figure 1A). There were no significant differences in the median particle size (70.5nm vs 65.5nm, p = 0.51) or concentration (4.59×10 12 /mL vs 3.05×10 12 /mL, p = 0.70) of EVs between the hypoxic and normoxic groups. (Figure 1B). miRNA sequencing revealed that hypoxia-derived EVs contained more miRNAs associated with anti-fibrotic gene regulation (Figure 1C and 1D). In the rat ICM (Ischemic Cardiomyopathy) model, echocardiographic assessment at 4 weeks post-administration revealed that the H-EV group exhibited significantly greater prevention of left ventricular diastolic diameter enlargement (7.3mm vs 8.0mm, p = 0.004) and systolic diameter enlargement (5.7mm vs 6.5mm, p = 0.0004), as well as improved ejection fraction (50% vs 43%, p = 0.0069), compared to the N-EV group (Figure 2A). Histologically, Picro-Sirius Red staining demonstrated a greater reduction in myocardial fibrosis in the H-EV group (7.3% vs 12.0%, p=0.044) (Figure 2B). Conclusions: In a rat model of ICM, EVs derived from hypoxic MSC cultures were enriched in anti-fibrotic miRNAs and exhibited superior therapeutic effects in terms of remodeling suppression and functional recovery compared to normoxic EVs.

Intraosseous adipose mesenchymal stem cells and plasma rich in growth factors: A promising approach for articular cartilage and subchondral bone regeneration.

Injectable dynamic hydrogel loaded with adipose-derived mesenchymal stem cells and verteporfin for enhanced scarless wound healing

miR-574-3p and miR-125a-5p in Adipose-Derived Mesenchymal Stem Cell Exosomes Synergistically Target TGF-β1/SMAD2 Signaling Pathway for the Treatment of Androgenic Alopecia.

Immunomodulatory effects of mesenchymal stromal cell secretome accelerate repair in a sickle cell disease wound model.

Glutamine: A novel player in maintaining skeletal strength and body fitness in obese mice.

hADMSC-Evs attenuates depressive and anxiety - like behaviors in chronic liver disease via suppressing Liver-Brain Galectin3 signaling.

ADSC-derived exosome-loaded in-situ photocrosslinkable GelMA hydrogels as a treatment strategy for wound healing.

Differential Effect of Two Transplantation Methods of Adipose-derived Mesenchymal Stem Cells on Hearing Improvement in Simulated Aging Rats.

Hepatic fibrosis is a serious illness that can lead to death. Until recently, there has been no effective medication to protect the liver and heal fibrosis. When thioacetamide (TAA)-induced hepatotoxicity occurred, we aimed to determine the hepatoprotective effectiveness of adipose, bone marrow, and liver-derived mesenchymal stem cells. Fifty male albino Wistar rats were used throughout the study and divided into 5 groups. Each group had 10 rats divided into 2 cages, 5 rats per cage. Forty male albino Wistar rats were injected intraperitoneally with 100 mg/kg of thioacetamide 2 times a week for 9 weeks. After 5 weeks of induction of liver fibrosis, forty rats were divided into four groups. One group was considered the TAA group and didn’t receive any treatment, and the other three groups were inoculated with a single dose of 3 × 106 BM-MSCs, AD-MSCs, and L-MSCs, respectively. We assessed the liver function tests as ALT, AST, and total bilirubin, which showed a significant decrease in groups inoculated with stem cells. But although the most significant decrease appeared in the L-MSCs inoculated group. Additionally, there was a notable rise in albumin levels in the L-MSC-inoculated group. In groups injected with stem cells, namely L-MSCs, the evaluation of antioxidant and oxidative stress levels revealed a substantial increase in GSH concentration, SOD activity, and CAT activity. Additionally, there is a noticeable drop in MDA and NO levels. By the ELISA technique, we assessed the hydroxyproline and collagen type-1, and the results showed a significant decrease in the groups inoculated with stem cells, especially L-MSCs. As well, this group showed a significant downregulation of ASMA gene expression. The percentage of fibrosis assessed in the histopathologic samples showed the most significant decrease in the L-MSCs inoculated group. In conclusion, our study showed that the different types of mesenchymal stem cells had an ameliorative effect on hepatic fibrosis, but the best results appeared with L-MSCs rather than BM-MSCs and AD-MSCs. The treated group with L-MSCs showed great enhancement in the antioxidant status, decreased hydroxyproline and collagen type-1 content, and a lower percentage of fibrosis.

Osteochondrodysplasia is a degenerative joint condition caused by a TRPV4 gene mutation, predominantly affecting Scottish Fold cats. This study evaluated the effects of adipose-derived mesenchymal stem cells (MSCs) in two Scottish Fold cats diagnosed with osteochondrodysplasia. Case 1 involved a 3-year-old cat with a one-month history of lameness and joint degeneration, while Case 2 featured a 4-year-old cat with a five-month history of similar symptoms. MSCs were isolated, characterized at passage 3, and administered intra-articularly at a dose of 1 × 10^6 cells/kg body weight. Both cats demonstrated significant clinical improvement, including resolution of lameness and increased mobility, despite persistent radiographic abnormalities. These findings suggest that MSC therapy may effectively alleviate clinical symptoms of osteochondrodysplasia. Further research is needed to explore its long-term efficacy and correlation with imaging outcomes.

Transoral laryngeal surgery (TOLS) may lead to glottic insufficiency and scarring which often causes pronounced hoarseness and sometimes swallowing impairment. Injection laryngoplasty with autologous fat is an established method to restore glottic competence and thus improve voice and swallowing function. We hereby aim to demonstrate how laryngeal fat injection can be applied following TOLS. Autologous fat is harvested via liposuction and then centrifuged for three minutes at 3000 rpm (rpm) to separate fat cells from liquid fat and debris. Fat cells are then transferred to 1 ml Luer-Lock syringes and injected into the altered larynx via a 20 Gauge (0,9 mm) diameter injection needle under microscopic or endoscopic view. The primary objective hereby is approximation of remaining tissue on the glottic plain. The secondary objective is injection into areas of scarified tissue due to the beneficial effect of Adipose-Derived Mesenchymal Stem Cells and possible restoration of physiological laryngeal tissue properties. Injection laryngoplasty with autologous fat tissue may improve laryngeal function after partial laryngeal resection by laser surgery. Special attention needs to be paid to the specific individual postoperative anatomy of the patient's larynx as this may differ profoundly from patient to patient.

Sepsis is a common and life-threatening condition encountered in intensive care units (ICUs). Mesenchymal stromal cells (MSCs) and their small extracellular vesicles (EVs) have emerged as promising nanotherapeutics, particularly in the context of COVID-19. This study evaluates the efficacy and mechanisms of adipose-derived MSC EVs (ADMSC-EVs) in a lipopolysaccharide (LPS)-induced sepsis model. We quantified M2 macrophages and IL-10 in peripheral blood mononuclear cells (PBMCs) from both septic patients and healthy donors. ADMSCs and their EVs were isolated, and EVs were administered to LPS-challenged mice.Macrophage phenotypes in lung tissue were analyzed using flow cytometry and immunofluorescence. The biodistribution of EVs was traced with PKH67 green fluorescent cell linker dye (PKH-67), and the signaling pathways involved in macrophage reprogramming were examined. ADMSC-EVs efficiently entered macrophages, promoted M2 polarization, suppressed inflammation, and improved survival rates in septic mice. Biodistribution studies demonstrated widespread organ accumulation, with notable localization in the lungs, liver, and kidneys.Mechanistically, the EV cargo miR-21-5p targetedPellino E3 ubiquitin protein ligase 1(PELI1), driving M2 polarization in vivo, which was accompanied by increased IL-10 levels. These findings position ADMSC-EVs as a viable cell-free therapeutic approach for mitigating LPS-induced sepsis through the delivery of miR-21-5p to PELI1, thereby supporting further development of EV-based immunomodulatory strategies for sepsis management.