Search Results (236)

Cartilage damage, particularly in the knee joint, presents a significant challenge in regenerative medicine due to its limited capacity for self-repair. Conventional treatments like microfracture surgery, autologous chondrocyte implantation (ACI), and osteochondral allografts often fall short, particularly in cases of larger defects or degenerative conditions. This has led to a growing interest in tissue engineering approaches that utilize biomaterial scaffolds to support cartilage regeneration. Among the many materials explored, chitosan—a naturally derived polysaccharide—has gained attention for its biocompatibility, biodegradability, and structural resemblance to the extracellular matrix (ECM) of cartilage. Recent advances in scaffold design have focused on modifying chitosan to improve its mechanical properties and enhance its biological performance. These modifications include chemical crosslinking, the incorporation of bioactive molecules, and the development of composite formulations. Such enhancements have allowed chitosan-based scaffolds to better support mesenchymal stem cell (MSC) differentiation into chondrocytes, paving the way for improved regenerative strategies. This review explores the latest progress in chitosan scaffold fabrication, preclinical findings, and the transition toward clinical applications. It also discusses the challenges that need to be addressed, such as mechanical stability, degradation rates, and the successful translation of research into viable therapeutic solutions. Full article

Mesenchymal stem cells (MSCs) exhibit low immunogenicity, multipotency, and are abundantly present in adipose tissue, making this tissue an easily accessible resource for regenerative medicine. Different commercial procedures have been developed to micro-fragment the adipose tissue aspirate from patients before its reinjection. We explored a commercial device which mechanically micro-fragments human lipoaspirate (LA) resulting in a homogeneous micro-fragmentation of fat tissue (MFAT). This device has been successfully employed in several clinical applications involving autologous adipose tissue transplantation. Here, we compare the untargeted/targeted lipidomic profile of LA and MFAT looking for differences in terms of qualitative modifications occurring during the handling of the original LA material. In MFAT, different lipid subclasses such as diacylglycerols, triacylglycerols, phospholipids, and sphingolipids are more represented than in LA. In addition, via targeted fatty acids analysis, we found a lower abundance of monounsaturated fatty acids in MFAT. The biological implications of these findings must be better investigated to contribute to a better understanding of the clinical efficacy of MFAT and for its potential use as a scaffold for drug delivery applications. Full article

Tissue defects resulting from craniomaxillofacial congenital developmental anomalies significantly compromise both the physical and psychological health of patients. Due to the constraints of autologous and allogeneic transplantation, stem cell-based regenerative therapies present a promising alternative. As a crucial source of cell therapy, mesenchymal stem cells (MSCs) are widely employed for tissue regeneration on account of their exceptional proliferative capacity and multidirectional differentiation potential. Nevertheless, several challenges remain in clinical application, such as the immunogenicity, long-term safety, and therapeutic efficacy. This review centers on the application of craniomaxillofacial MSCs in the treatment of craniomaxillofacial congenital defects and the challenges confronted in regenerative therapy, aiming to provide new perspectives for the clinical management of these conditions. Full article

The impact of donor age on Adipose-derived mesenchymal stem cell (ASC) functionality and safety remains insufficiently characterized, particularly in equine models. This study investigates the influence of age on ASCs proliferation dynamics and the expression of tumorigenic and apoptosis-related markers. Equine ASCs were isolated from juvenile (<5 years), middle-aged (5–15 years), and geriatric (>15 years) horses and assayed across multiple passages. The relative mRNA expressions of pluripotency (Oct4), tumorigenic (CA9), and apoptosis-related (Bax and Bcl 2) markers were evaluated. The Gompertz growth model, population doubling time (PDT), and tissue non-specific ALP activity also followed. The expression of pluripotency and tumorigenic markers showed passage-dependent up-regulation, raising concerns about prolonged culture expansion. Apoptotic regulation displayed a shift with aging, as evidenced by alterations in the Bax/Bcl2 ratio, suggesting compromised cell survival in older ASCs. An age-associated decline in proliferation rates was established, as evidenced by declining alkaline phosphatase (ALP) activity. These findings underscore the necessity for stringent age-based selection criteria in equine stem cell therapies and the challenges associated with using autologous stem cells for regenerative therapies in aged horses. Future research should focus on molecular interventions to mitigate age-related functional decline, ensuring the safety and efficacy of ASCs-based regenerative medicine in equine practice. Full article

Age-related macular degeneration (AMD) is a common cause of blindness worldwide, and it is projected to affect several million individuals by 2040. The human retinal pigment epithelium (hRPE) degenerates in dry AMD, prompting the need to develop stem cell therapies to replace the lost tissue by autologous transplantation and restore the visual function. Nevertheless, the molecular factors behind the hRPE cell fate determination have not been elucidated. Here we identify all molecular determinants of the hRPE cell fate identity by comprehensive and unbiased screening of predicted pioneer factors in the human genome: such TFs mediate coordinated transitions in chromatin accessibility and transcriptional outcome along three major stages of the hRPE genesis. Furthermore, we compile a complete census of all transcription factor-specific binding sites by footprinting analysis of the human epigenome along the RPE developmental trajectory. Gene regulatory networks were found to be involved in cellular responses to glucose and hypoxia, RPE nitrosative stress, type II epithelial-to-mesenchymal transition (EMT), and type III tumorigenic EMT, providing routes for therapeutic intervention on pleiotropic targets dysregulated in AMD, diabetic retinopathy, and cancer progression. Genome editing technologies may leverage this repository to devise functional screenings of regulatory elements and pharmacogenomic therapies in complex diseases, paving the way for strategies in precision medicine. Full article

Cartilage-derived migratory cells show great potential for autologous use in cartilage repair surgery. However, their collection through arthroscopic biopsy has not been previously reported in individuals without osteoarthritis. This study aimed to characterize migratory cartilage cells isolated from arthroscopic biopsies of volunteers without osteoarthritis and compare them with cells obtained by enzymatic digestion. Cell cultures were successfully established using both methods—enzymatic digestion and cell migration—from cartilage explants, with no significant differences observed in stem cell markers or plasticity between the cell lines. Cells derived from both procedures exhibited characteristics of mesenchymal stem cell, including fibroblast-like morphology, expression of CD29, CD90, and CD105 markers, absence of hematopoietic and endothelial cell markers, and the ability to differentiate into adipocytes, chondrocytes, and osteoblasts under appropriate conditions. Cells obtained by migration showed lower expression of collagen I and II, along with reduce collagen II/collagen I ratio, both positively associated with chondral matrix production, as well as lower RUNX2 expression. However, no differences were found in the levels of SOX9, essential for chondrogenic differentiation, or in the expression of perlecan gene. Syndecan-1 expression was lower in cells obtained by migration. In conclusion, this study demonstrates that cartilage-derived migratory cells can be successfully obtained from arthroscopic biopsies of individuals without osteoarthritis, presenting comparable dedifferentiation and plasticity profiles. Furthermore, these cells express essential chondrogenic markers and proteins. Although further in vivo studies are needed to determine their effective regenerative potential, cartilage-derived migratory cells represent a promising avenue for cartilage repair strategies. Full article

Background: Mesenchymal stem cell-based therapy may be indicated in ischaemic heart disease. The use of autologous adipose-derived mesenchymal stromal cells (AdMSCs) offers regenerative potential due to their paracrine effects. The aim of this study was to expand and characterise adult human thymus-derived MSCs harvested during open heart surgery with respect to their stem cell and paracrine properties. Methods: Enzymatically and non-enzymatically isolated human thymic AdMSCs (ThyAdMSCs) were cultured in xeno-free media containing pooled human platelet lysate (pPL). MSC characterisation was performed. Ex vivo expanded ThyAdMSCs were differentiated into three lineages. Proliferative capacity and immunomodulatory properties were assessed by proliferation assays and mixed lymphocyte reaction, respectively. Gene expression analysis was performed by qPCR. Results: Both isolation methods yielded fibroblast-like cells with plastic adherence and high proliferation. Flow cytometry revealed distinct expression of MSC markers in the absence of haematopoietic cell surface markers. Ex vivo expanded ThyAdMSCs could be differentiated into adipocytes, osteocytes, and chondrocytes. Activated peripheral blood mononuclear cells were significantly reduced when co-cultured with ThyAdMSCs, indicating their ability to inhibit immune cells in vitro. Gene expression analysis showed significantly less IFNγ and TNFα, indicating an alteration of the activated and pro-inflammatory state in the presence of ThyAdMSCs. Conclusions: These results demonstrate an efficient method to generate AdMSCs from human thymus. These MSCs have a strong immunomodulatory capacity and are, therefore, a promising cell source for regenerative medicine. The culture conditions are crucial for cells to proliferate in culture. Further research could explore the use of ThyAdMSCs or their secretome in surgical procedures. Full article

Bone marrow aspirate concentrate (BMAC) is an autologous regenerative therapy enriched with mesenchymal stem cells (MSCs) and bioactive growth factors, offering potential disease-modifying effects in knee osteoarthritis (OA). Compared to conventional intra-articular treatments, including hyaluronic acid (HA), platelet-rich plasma (PRP), and corticosteroids, BMAC promotes cartilage regeneration, modulates inflammation, and enhances subchondral bone remodeling. Clinical evidence suggests that BMAC provides short- to mid-term symptomatic relief and functional improvement, with some studies indicating a potential to delay total knee arthroplasty (TKA). However, findings remain inconsistent, and long-term efficacy compared to PRP or autologous conditioned serum (ACS) is yet to be firmly established. Variability in BMAC preparation methods, injection protocols (single vs. repeated administration, intra-articular vs. subchondral delivery), and patient selection criteria complicates its clinical application, highlighting the need for standardized guidelines. Additionally, economic feasibility and cost-effectiveness concerns limit its widespread adoption. This review synthesizes current clinical evidence, evaluates optimal administration strategies, and explores future directions for improving treatment standardization and patient-specific therapy. Future research should prioritize well-designed, multicenter randomized controlled trials (RCTs) with long-term follow-up to confirm the sustained efficacy and therapeutic potential of BMAC in OA management. Full article

Background: Sjögren’s syndrome (SS) is a systemic autoimmune condition marked by significant dry eye disease (DED), leading to considerable corneal changes. These modifications, encompassing punctate epithelial erosions, chronic epithelial abnormalities, and corneal ulcers, significantly impact eyesight and quality of life. Progress in comprehending the corneal pathophysiology associated with SS has prompted innovative diagnostic and treatment approaches. Aim: This narrative review aims to examine developing trends in the pathogenesis, diagnostic methods, and treatment strategies for Sjögren’s syndrome-associated corneal changes. Methods: The study was based on a narrative review of the current literature available on PubMed and Cochrane from Jan 2000 to December 2024. Results: Corneal changes associated with Sjögren’s syndrome result from a multifactorial interaction of ocular surface inflammation, tear film instability, and epithelium degradation. Recent research underscores the significance of immune-mediated pathways, such as T-cell-induced inflammation and cytokine dysregulation, as crucial factors in corneal disease. Innovations in diagnostic instruments, including in vivo confocal microscopy and tear proteomics, provide earlier and more accurate identification of subclinical alterations in the corneal epithelium and stroma. Therapeutic developments concentrate on meeting the specific requirements of SS-related DED. Biological treatments, especially tailored inhibitors of interleukin-6 and tumor necrosis factor-alpha, show potential in mitigating inflammation and facilitating epithelial repair. Moreover, regenerative approaches, such as autologous serum tears and mesenchymal stem cell therapies, provide innovative methods to repair ocular surface integrity. Advanced drug delivery technologies, including nanoparticle-loaded eye drops, enhance bioavailability and therapeutic efficacy. Conclusion: Recent developments in comprehending SS-related corneal changes have transformed the management approach to precision medicine. The combination of improved diagnostics and innovative therapy approaches offers potential for reducing disease progression, maintaining corneal health, and enhancing patient outcomes. Subsequent investigations ought to concentrate on enhancing these tactics and examining their long-term safety and effectiveness. Clinicians and researchers must adopt these developments to successfully tackle the difficulties of SS-related corneal illness, providing hope for improved care and higher quality of life for those affected. Full article

Background/Objectives: Mandibular reconstruction following trauma or oncologic resection is crucial for restoring function and aesthetics. While autologous bone grafting remains the gold standard, it presents challenges such as donor site morbidity and graft availability. Bone tissue engineering (BTE) offers an innovative alternative, integrating scaffolds, osteogenic cells, and bioactive factors to regenerate functional bone. This systematic review evaluates BTE strategies for mandibular reconstruction, focusing on critical-sized defects in large animal models and their translational potential for clinical applications. Methods: A systematic review was performed following PRISMA guidelines. Eligible studies involved large animal models and critical-sized mandibular defects treated with at least two BTE components (scaffold, osteogenic cells, or growth factors). Quality and bias assessments were conducted using ARRIVE guidelines and SYRCLE tools. Results: Of the 6088 studies screened, 27 met the inclusion criteria, focusing on critical-sized mandibular defects in large animal models such as pigs, sheep, and dogs. Common scaffolds included β-tricalcium phosphate (β-TCP), poly-lactic-co-glycolic acid (PLGA), and polycaprolactone (PCL), frequently combined with bone marrow-derived mesenchymal stem cells (BMSCs) and growth factors like recombinant human bone morphogenetic protein-2 (rhBMP-2). Preclinical outcomes demonstrated effective bone regeneration, vascularization, and biomechanical restoration. Advanced strategies, including in vivo bioreactors and 3D-printed scaffolds, further enhanced regeneration. However, challenges such as incomplete scaffold degradation, hypoxic conditions within constructs, and variability in growth factor efficacy and dose optimization were observed, emphasizing the need for further refinement to ensure consistent outcomes. Conclusions: BTE shows promise in mandibular reconstruction, achieving bone regeneration and functional restoration in preclinical models of critical-sized defects. However, challenges such as scaffold optimization, vascularization enhancement, and protocol standardization require further investigation to facilitate clinical translation. These findings emphasize the need for refinement to achieve consistent, scalable outcomes for clinical use. Full article

Background/Objectives: Regenerative therapies have gained interest in orthopedic applications for their potential to enhance tissue regeneration, functional recovery, and pain modification. This review evaluates the clinical efficacy of platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), peptide-based treatments, and biomimetic materials in orthopedic care, with a focus on pain reduction and functional outcomes. Methods: A structured literature search in PubMed (January 2009–January 2025) identified 160 studies. After applying inclusion criteria prioritizing randomized controlled trials (RCTs) and clinical trials, 59 studies were included: 20 on PRP, 20 on MSCs, 10 on peptide therapies, and 7 on biomimetics. Data extraction focused on pain reduction and functional recovery, with risk of bias assessed using the Cochrane Risk of Bias (RoB) tool and ROBINS-I tool. A random-effects meta-regression analysis was conducted to evaluate the impact of therapy type, sample size, and risk of bias on reported pain reduction outcomes. Results: Meta-regression analysis identified MSC therapy as the most effective intervention for pain reduction (β = 8.45, p < 0.05), with PRP and peptide-based therapies showing moderate improvements, and biomimetic therapies demonstrating the lowest effect. PRP provided short-term pain relief, particularly in acute injuries and tendon repair, though inconsistencies in preparation methods limited success in chronic conditions. MSC therapies demonstrated cartilage regeneration and early osteoarthritis improvement, but high costs and ethical concerns remain barriers to widespread adoption. Peptide-based therapies and biomimetic materials, including engineered scaffolds and autologous protein solutions, showed promise for infection control and wound healing, though further research is needed to optimize dosing, delivery methods, and long-term safety. Conclusions: Regenerative therapies offer significant potential in orthopedic care, with MSC therapies demonstrating the most reliable regenerative effects, PRP providing short-term symptomatic relief, and peptide-based and biomimetic treatments emerging as promising adjuncts. However, standardized protocols and large-scale clinical trials are needed to establish long-term efficacy and improve clinical translation for broader adoption. Full article

The use of autologous biological preparations (ABPs) and their combinations fills the void in healthcare treatment options that exists between surgical procedures, like plastic reconstructive, cosmetic, and orthopedic surgeries; non-surgical musculoskeletal biological procedures; and current pharmaceutical treatments. ABPs, including high-density platelet-rich plasma (HD-PRP), bone marrow aspirate concentrates (BMACs), and adipose tissue preparations, with their unique stromal vascular fractions (SVFs), can play important roles in tissue regeneration and repair processes. They can be easily and safely prepared at the point of care. Healthcare professionals can employ ABPs to mimic the classical wound healing cascade, initiate the angiogenesis cascade, and induce tissue regenerative pathways, aiming to restore the integrity and function of damaged tissues. In this review, we will address combining autologous HD-PRP with adipose tissue, in particular the tissue stromal vascular fraction (t-SVF), as we believe that this biocellular combination demonstrates a synergistic effect, where the HD-PRP constituents enhance the regenerative potential of t-SVF and its adipose-derived mesenchymal stem cells (AD-MSCs) and pericytes, leading to improved functional tissue repair, tissue regeneration, and wound healing in variety of clinical applications. We will address some relevant platelet bio-physiological aspects, since these properties contribute to the synergistic effects of combining HD-PRP with t-SVF, promoting overall better outcomes in chronic inflammatory conditions, soft tissue repair, and tissue rejuvenation. Full article

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease affecting all organ systems. The disease preferentially affects females of childbearing age. It runs a variable course. It may run a mild course that may never lead to severe disease and manifestations from critical organ systems. However, it may also run an undulating course with periods of mild and severe disease. It may run as a mild disease, quickly deteriorating to severe disease and affecting multiple organ systems. Various immune pathways related both to the innate and adaptive immune response are involved in the pathogenesis of SLE. Various drugs have been developed targeting cellular and molecular targets in these pathways. Interferons are involved in the pathogenesis of SLE, and various drugs have been developed to target this pathway. T and B lymphocytes are involved in the pathophysiology of SLE. Various treatment modalities targeting cellular targets are available for the treatment of SLE. These include biologic agents targeting B lymphocytes. However, some patients have disease refractory to these treatment modalities. For these patients, cell-based therapies may be used. Hematopoietic stem cell transplantation involving autologous cells is an option in the treatment of refractory SLE. Mesenchymal stem cells are also applied in the treatment of SLE. Chimeric antigen receptor (CAR)-T cell therapy is a novel treatment also used in SLE management. This novel treatment method holds major promise for the management of autoimmune diseases and, in particular, SLE. Major hurdles to be overcome are the logistics involved, as well as the need for specialized facilities. This review focuses on novel treatment modalities in SLE targeting cellular and molecular targets in the immune system. Full article

Osteoarthritis (OA) is a prevalent joint disorder that lacks effective therapies to halt cartilage degeneration. Mesenchymal stromal cell (MSC)-derived small extracellular vesicles (sEVs) are being investigated as promising chondroprotective agents. Compared to primary MSCs, induced pluripotent stem cell (iPSC)-derived MSCs (MLCs) offer superior scalability and enhanced paracrine activity. The aim of this study was to explore the feasibility of using autologous MLC-derived sEVs as a potential therapeutic strategy for OA through the analysis of their protein cargo. iPSCs from an OA patient and a healthy donor were differentiated into MLCs. sEVs were isolated from these MLCs and characterized, with a particular focus on their protein cargo. Both iPSC lines were successfully differentiated into MLCs, which secreted sEVs with comparable size distributions and yields. The analysis of differentially expressed proteins revealed a high abundance of proteins associated with OA pathology and cartilage degradation in sEVs from OA MLCs compared to those from healthy MLCs. The persistence of OA-associated protein signatures in autologous MLC-derived sEVs may limit their therapeutic efficacy. These findings underscore the importance of carefully evaluating disease-specific protein profiles in sEVs for regenerative applications. Full article

Urine-derived mesenchymal stromal/stem cells (USCs) could be a valuable source of cells in regenerative medicine because urine can be easily collected non-invasively. In this paper, USCs were isolated from both healthy dogs and dogs affected by chronic kidney disease (CKD), and the efficacy of collection methods (spontaneous micturition, bladder catheterization, and cystocentesis) were compared. Isolated cells were cultured in the presence of platelet-rich plasma and studied for their proliferative capacity (growth curve, doubling time, and colony forming unit), differentiation properties, expression of mesenchymal markers, and Klotho protein. Morphologically, all cells were elongated and fibroblast-like. USCs isolated from samples collected by spontaneous micturition and bladder catheterization failed to proliferate, whilst USCs obtained by cystocentesis showed a doubling time of 2.04 days in healthy dogs and 1.7 days in dogs with CKD (p < 0.05). Cells were able to differentiate into osteogenic, chondrogenic, and adipogenic lines, showed positive expression to mesenchymal/stem markers, negative expression to hematopoietic markers, and major histocompatibility complex (MHCII) antigen. Klotho protein expression was confirmed. This study confirmed that USCs from healthy and CKD dogs can act as stem cells, with those from sick dogs having greater proliferative ability with the potential for use as autologous therapies. Full article