Search Results (862)

Background/Objectives: Modern approaches for post-stroke rehabilitation cover mechanistically different ways—from physiotherapy to digital technologies. Among these approaches, stem cell-based therapy represents probably the most complex but promising strategy. Methods: We discuss the current state-of-the-art of using mesenchymal stem cells (MSCs) in post-stroke regenerative therapy. Despite relatively wide use of bone marrow and adipose tissue MSCs, these cells represent a more mature (“adult”) state, which limits their proliferative and regenerative potentials. Compared to the “adult” MSCs, less “mature” MSCs obtained from umbilical cord, specifically Wharton’s jelly MSCs (WJ-MSCs), demonstrate unique functional capabilities and are free from certain technical and ethical issues. Results: The molecular and cellular mechanisms of action of WJ-MSCs are thoroughly discussed in comparison with abundantly used “adult” types of MSCs. We also comparatively evaluate their preclinical and clinical application for treating post-stroke patients. Recent findings indicate that not only MSCs but also their secretome/exosomes (cell-free product) represent a therapeutically beneficial cellular drug in post-stroke recovery. Specially designed and carefully evaluated protocols, which preserve the bioactivity of the cell-free product intact, are mentioned. Neuroprotective and neuroreparative properties of cell-free products—secretome and exosomes—derived from Wharton’s jelly MSCs are summarized. Conclusions: Cell-free products obtained from WJ-MSCs are an innovative adjunct therapy for post-stroke disorders, despite certain challenges and limitations of this type of therapy still present. By further investigation of the molecular composition and biological mechanisms of the WJ-MSC secretome and exosomes, their clinical applicability in neuroinflammatory and neurodegenerative pathologies will be promoted. Full article

Background: Platelet concentrates are widely used in regenerative dentistry and maxillofacial surgery; however, the lack of protocol standardization and selection criteria results in contradictory clinical outcomes. This study aimed to perform a comparative analysis of the biological activity of various platelet concentrates obtained via different fractionation and activation procedures under uniform in vitro experimental conditions. Methods: Rat adipose-derived stem cells (ADSCs) and human EA.hy926 endothelial cells were used to evaluate four platelet concentrate types via tube formation, wound healing (scratch), and cell proliferation assays. Results: Platelet concentrates obtained by the single-centrifugation protocol (L-PRP-1) exhibited maximal retained platelet potential, corresponding to a peak 5-fold increase in cell migration. Chemical activation of plasma-based concentrates (L-PRP, P-PRP) with calcium/thrombin was critically required to trigger angiogenesis and accelerate endothelial chemotaxis. Conversely, plasma-free platelet concentrate (PFPC) exhibited a unique capacity for spontaneous activation and clot formation without exogenous inducers, triggering rapid angiogenesis and sustaining ADSC proliferation. Conclusions: Within the framework of our in vitro model, activated plasma-based forms are biologically justified for accelerated soft tissue healing and socket preservation, whereas the complete removal of plasma proteins suggests the potential utility of PFPC as a biomimetic matrix-carrier for maxillofacial tissue engineering. Full article

Coronary artery calcification (CAC) is a pressing issue in cardiology. Mesenchymal stem cells (MSCs) derived from epicardial adipose tissue (EAT) may serve as a source of osteoblasts in the cardiovascular system. This study aimed to evaluate and compare the immunophenotype, proliferation, and osteogenic potential of EAT-MSCs from patients with coronary artery disease (CAD) and those with aortic stenosis (AS). The immunophenotype of MSCs was analyzed based on key markers: CD105, CD90, CD73, CD31, CD34, CD45, HLA-DR. Cell proliferation was assessed by the doubling time of the population and the specific growth rate of the cultures. The osteogenic potential was evaluated by the expression levels of the RUNX2, SPP1, ALPL, and BGLAP genes using PCR, as well as the protein levels in supernatants via ELISA. Qualitative detection of osteogenic proteins in cells by immunofluorescence staining. The intensity of extracellular matrix mineralization was measured using photometric methods. CD73 expression in EAT-MSCs from CAD patients was nearly 50% lower than in EAT-MSC cultures from AS patients. Following osteogenic induction, EAT-MSCs from CAD patients showed increased expression of osteogenic marker genes and their corresponding proteins. The intensity of extracellular matrix mineralization by osteoblasts derived from EAT-MSCs of CAD patients was higher than in the comparison group. EAT-MSCs from CAD patients with coronary calcification demonstrated reduced CD73 expression in culture and enhanced osteogenic potential compared to patients without coronary artery involvement. Full article

Micro-fragmented adipose tissue (mFAT) is a promising autologous biologic in regenerative medicine because it provides a mechanically processed adipose-derived product that preserves native extracellular matrix architecture and a cellular milieu rich in mesenchymal stem cells, pericytes, growth factors, cytokines, and extracellular vesicles. Mechanistically, mFAT is hypothesized to act largely through paracrine signaling that dampens inflammation, supports vascular stabilization, and promotes cartilage and soft-tissue repair; in vitro data suggest modulation of osteoarthritic synovial macrophage signaling, including reductions in chemokines such as CCL2 and CCL3. Preparation involves liposuction harvest followed by closed, sterile mechanical processing without enzymatic digestion or cell expansion, aligning with “minimal manipulation” concepts relevant to regulatory frameworks. Preclinical animal studies generally demonstrate favorable effects on synovial inflammation and cartilage matrix markers (e.g., glycosaminoglycan content) with limited adverse events. Clinically, the strongest body of evidence is in knee osteoarthritis, where multiple prospective and retrospective studies report improvements in pain and function from months to several years after single injections, though response rates vary and study designs are heterogeneous. Evolving data support potential benefit in hip osteoarthritis and select tendon conditions, but cohorts remain small. Overall, mFAT appears safe and potentially effective, yet larger, standardized, long-term randomized controlled trials and comparative studies versus platelet-rich plasma and bone marrow aspirate concentrates are needed to clarify indications, dosing, durability, and mechanisms in vivo. Full article

Peripheral nerve injuries (PNI) present a major clinical and socioeconomic challenge due to limited regenerative capacity. Adipose-derived stem cells (ADSCs) within the stromal vascular fraction (SVF) of white adipose tissue offer a promising autologous source for regenerative support. This study evaluated the impact of mechanical processing CELT (Cell-Enriched Lipotransfer) and CELT^PLUS and electrical stimulation on the regenerative secretome of human lipoaspirates. qPCR analysis revealed that CELT^PLUS processing, which incorporates mechanical intersyringe shifting, significantly doubled the gene expression of nerve growth factor (NGF) (p = 0.015), vascular endothelial growth factor (VEGF) (p = 0.02), and brain-derived neurotrophic factor (BDNF) (p = 0.04) compared to CELT-processed lipoaspirate. Protein analysis via ELISA confirmed a time-dependent secretion of NGF and VEGF over 96 h. Furthermore, 24 h electrical stimulation (2 V) significantly enhanced NGF protein release (p < 0.001). These findings demonstrate that standardized mechanical processing effectively enriches regenerative cell populations and amplifies their neurogenic and angiogenic potential. The additional modulation of growth factor secretion via electrical stimulation highlights the potential of processed adipose tissue as a functional, autologous transplant for enhanced nerve reconstruction. Full article

Background: Osteoarthritis involves the degeneration of cartilage, subchondral bone, and the synovial membrane, often associated with rotator cuff (RC) tears, causing pain and functional limitations. While non-surgical treatments can provide relief, surgery is sometimes necessary. Autologous adipose-derived mesenchymal stem cells (ADMSCs) have shown promise in tissue repair. Objective: This study compared clinical outcomes between patients treated with arthroscopic RCR alone and those treated with RCR combined with intra-articular AdMSC injection. Methods: This retrospective study included 61 patients. Group A (n = 30) underwent standard RCR, while Group B (n = 31) received RCR combined with intra-articular ADMSC injections. Participants had comparable baseline age, BMI, height, CMS, and VAS scores. Shoulder function was assessed using the Constant–Murley Score, and pain intensity was assessed using the visual analog scale at baseline, 3, 6, and 12 months. Statistical significance was set at p < 0.05. Results: At 3 months, Group B showed lower VAS scores than Group A (13.09 ± 8.34 vs. 25.14 ± 13.57, p < 0.001), while CMSs did not differ significantly (70.55 ± 23.46 vs. 63.01 ± 24.33, p = 0.223). At 6 months, Group B showed better VAS and CMSs than Group A (VAS: 5.31 ± 4.38 vs. 23.74 ± 15.72, p < 0.001; CMS: 83.29 ± 18.98 vs. 65.66 ± 11.58, p < 0.001). At 12 months, Group B maintained better VAS and CMSs than Group A (VAS: 4.45 ± 5.67 vs. 18.34 ± 12.65, p < 0.001; CMS: 85.55 ± 13.12 vs. 66.36 ± 9.38, p < 0.001). Conclusions: In this preliminary retrospective non-randomized cohort, AdMSC use as an adjunct to arthroscopic rotator cuff repair was associated with better pain and functional scores over 12 months. Because of the retrospective design and lack of imaging follow-up, these findings should be interpreted as clinical associations and require confirmation in randomized studies. Full article

Liver fibrosis is a severe but common disease without an easy-to-access option for efficient treatment. Mesenchymal stem cells (MSCs) of different origins have been tested for antifibrotic effects in vitro, in vivo, and in clinical studies over the two last decades, although the comparative efficiency of different subtypes remains not fully understood, especially for long-term survival. In this study, we aimed to compare the long-time persistence of favorable effects in male Wistar rats with liver fibrosis treated using MSCs derived from white adipose tissue (AdMSCs) and bone marrow (BMSCs). Liver fibrosis was induced by carbon tetrachloride. We studied the survival rate; oxidative index, assessed via laser Doppler flowmetry; hepatic markers in blood plasma—albumin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase; the ratio of liver to body mass; histological parameters—the number of adipocytes, lymphocytes, siderophages, and Ki67⁺ cells; and the relative areas of connective tissue proper and reticular fibers. Extra mortality was only typical for fibrotic animals subjected to the sham treatment in the first two weeks. Up to Day 270 of this study, both MSC-treated groups showed barely any differences from animals undergoing the sham treatment in terms of the oxidative index and blood markers, although AdMSC-treated rats presented a more favorable histological pattern than BMSC-treated ones, considering the relative area of reticular fibers and the Ki67 cell count. This study suggests that AdMSC treatments may be more appropriate than BMSC treatments in animal liver fibrosis models, with the results showing better potential for liver tissue regeneration 9 months after treatment. Full article

Lipedema is a chronic adipose tissue disorder characterized by disproportionate and often painful enlargement of the extremities, occurring predominantly in women. Despite increasing clinical recognition, the underlying pathophysiology remains incompletely understood and is likely multifactorial. Existing evidence suggests contributions from vascular alterations, adipose tissue remodeling, inflammatory activation, hormonal influences, and lymphatic dysfunction. This review proposes a hypothesis-generating integrative framework in which lipedema may reflect a regenerative imbalance of subcutaneous adipose tissue. Within this model, genetically and hormonally modulated endothelial permeability could promote activation of perivascular adipose-derived stromal/stem-cell niches and stromal vascular fraction signaling pathways, thereby facilitating coupled angiogenesis and adipogenesis. Progressive adipocyte hyperplasia and hypertrophy may subsequently contribute to inflammatory remodeling, pain generation, and secondary impairment of dermal and subdermal lymphatic drainage. The proposed framework attempts to integrate clinical, histological, imaging, molecular, and endocrine observations into a biologically coherent conceptual model. At the same time, the review emphasizes the current limitations of the available evidence, the heterogeneity of lipedema phenotypes, and the ongoing controversies regarding disease progression, obesity overlap, and the relative role of lymphatic dysfunction. Finally, the potential mechanistic rationale of lymphatic-sparing liposuction is discussed in the context of tissue decompression, restoration of lymphatic transport, and interruption of persistent adipose remodeling. The model presented here should be interpreted as a hypothesis-generating conceptual scaffold requiring prospective validation. Importantly, the present framework should be interpreted as a biologically plausible and hypothesis-generating conceptual model rather than a definitive mechanistic doctrine. Several proposed interactions remain associative and require prospective biological validation. Full article

Background/Objectives: Obesity and menopause are major determinants of skeletal deterioration; however, their combined effects on bone remodeling and associated cellular bioenergetics remain incompletely understood. This study aimed to determine whether obesity induces osteoporotic alterations under both estrogen-replete and estrogen-deficient conditions and to evaluate the therapeutic potential of dental tissue-derived mesenchymal stem cells (D-MSCs). Methods: Female mice were subjected to ovariectomy (OVX) and/or high-fat diet (HFD) feeding for 16 weeks to establish obesity-associated osteoporosis models. D-MSCs were administered intraperitoneally at defined intervals. Body weight and serum leptin levels were measured to assess metabolic status. Femoral tissues were analyzed by quantitative real-time PCR for estrogen receptors (ERα, ERβ), inflammatory markers (Il-1β, Tnf-α), mitochondrial regulators (Pgc1α, Pgc1β), and the OPG/RANKL ratio. Histological analysis was performed to evaluate bone marrow adiposity. Results: HFD significantly increased body weight and serum leptin levels in both intact and OVX mice. Obesity was associated with reduced expression of ERα and ERβ, decreased Pgc1α levels, and a lower OPG/RANKL ratio, accompanied by increased Il-1β, Tnf-α, and Pgc1β expression. D-MSC administration attenuated body weight gain and reduced leptin levels, particularly in OVX mice. In femoral tissue, D-MSC treatment restored estrogen receptor expression, increased Pgc1α, decreased Pgc1β, and normalized the OPG/RANKL ratio. In addition, inflammatory marker expression and bone marrow adiposity were reduced following MSC administration. Conclusions: Obesity induces bone remodeling dysregulation under both intact and estrogen-deficient conditions, characterized by altered estrogen signaling, inflammatory activation, and mitochondrial imbalance. D-MSC administration was associated with partial restoration of these alterations, suggesting a potential role in modulating metabolic and skeletal homeostasis in obesity-associated bone loss. Full article

Nervous system and corneal disorders are major causes of permanent disability worldwide, largely due to the limited regenerative capacity of ectoderm-derived tissues. Therefore, the development of accessible and ethically acceptable cell-based therapies promoting the repair and regeneration of these tissues is of considerable translational importance. In this study, we aimed to comparatively evaluate the ectodermal differentiation potential of human adipose-derived stem cells (ADSCs) and human amniotic epithelial cells (hAECs) in vitro, with hAECs serving as a reference cell population with established ectodermal plasticity. Primary ADSCs and hAECs were characterized phenotypically using flow cytometry and functional differentiation assays. Cells were subjected to a directed ectodermal differentiation protocol and assessed via morphological analysis, immunostaining for ectoderm-associated proteins, and RT-qPCR analysis of lineage-specific genes. ADSCs exhibited morphological changes following differentiation, including a more epithelial-like phenotype and an increased nucleus-to-cytoplasm ratio. Immunostaining revealed the induction of nestin and OTX2 expression after differentiation, which was particularly pronounced in ADSCs. Gene expression analysis demonstrated statistically significant upregulation of the ectoderm-related genes EN2, SOX1, and PAX6 exclusively in hAECs. Results suggest that in ADSCs the differentiation process was only partially activated. In conclusion, our findings further support the suitability of hAECs as a reference cell line for studies investigating ectodermal differentiation protocols, while also demonstrating that ADSCs exhibit a limited but detectable capacity for acquiring ectoderm-specific characteristics under defined in vitro culture conditions. Full article

Introduction: Chronic wounds and pathologic scars remain a persistent challenge in plastic surgery. Conventional treatments can be costly and inconsistent, prompting interest in regenerative approaches that utilize autologous tissue. Emulsified fat produces nanofat through mechanical processing and contains adipose-derived stem cells, stromal vascular fractions, extracellular matrix proteins, cytokines and growth factors. The purpose of this systematic review is to evaluate the use of autologous nanofat for wound healing and scar management, with emphasis on preparation techniques, treatment indications, and outcomes. Methods: A comprehensive PubMed search with no date restrictions was conducted in January 2026 using MeSH terms and keywords related to nanofat and wound-healing applications. Studies were screened independently by two reviewers using the Rayyan platform. Eligible studies evaluated nanofat for wound healing in human or animal subjects; non-English articles, studies not involving nanofat, editorials, and conference abstracts were excluded. The extracted data included study characteristics, participant numbers, treatment details, indications, adjunct therapies, follow-up duration, outcomes, and complications. Studies were grouped by clinical application, with individual reports included in multiple categories when relevant. Results: The search identified 53 records, of which 22 studies met the inclusion criteria after screening. These included 20 human and two animal studies spanning randomized controlled trials (n = 3), prospective trials (n = 6), retrospective analyses (n = 6), case series (n = 4), and case reports (n = 3). Mechanical emulsification was the predominant autologous nanofat preparation method (91%), often combined with filtration or centrifugation. Clinical indications in human studies were diverse, most commonly including scar treatment (n = 14) (acne, burns, depressed, and post-surgical), followed by chronic wounds (n = 3) and reconstructive applications (n = 3). Nanofat was administered via injection in 86% of studies (n = 19), typically using fine-gauge needles or microcannulas with intradermal or subdermal placement, while three studies used non-injection approaches such as topical, membrane, or dressing-based delivery. Scar or aesthetic parameters, measured using VSS, POSAS, physician grading, photography, pigmentation analysis, or clinical appearance, were evaluated in 73% of studies (n = 16), and all reported improvement in variables such as pigmentation, pliability, thickness, texture, or overall appearance. Wound-healing endpoints were assessed in 36% (n = 8), with 100% (n = 8) demonstrating accelerated healing, improved epithelialization, or defect closure. Patient-reported outcomes, including satisfaction or quality of life, were measured in 32% (n = 7), and all showed improvement. Objective imaging modalities (e.g., 3D imaging, ultrasound, angiography, digital analysis) were used in 23% (n = 5), each confirming structural or physiologic improvement. Histologic or biomolecular analyses were performed in 27% (n = 6) and uniformly demonstrated regenerative changes, such as increased angiogenesis, collagen remodeling, or growth factor expression. Treatment was well tolerated, with 77% of studies (n = 17) reporting minimal or no complications and only transient mild adverse effects, including mild pain, bruising, erythema, and edema. Conclusions: Current evidence suggests that autologous nanofat is a promising regenerative therapy for wound healing and scar modulation. Across diverse clinical applications, nanofat has been associated with improved tissue quality, enhanced healing, and favorable patient-reported outcomes, with minimal complications. The mechanical processing of autologous tissue may also involve fewer regulatory concerns compared with more extensively manipulated cellular products. Full article

Mesenchymal stromal cells derived from adipose tissue (ASCs) are widely used in regenerative medicine, requiring scalable expansion strategies that preserve both cellular function and biological quality. However, current bioprocess optimization approaches are primarily guided by proliferation and phenotypic stability, often overlooking genomic integrity as a critical attribute. In this study, we developed a stirred-tank bioreactor system for ASC expansion on microcarriers and applied a genotoxicity-informed optimization strategy by integrating growth kinetics, metabolic profiling, and DNA damage assessment across multiple operational conditions (B₁–B₅), including variations in dissolved oxygen, agitation, inoculum density, and medium renewal. Optimized culture conditions (B5) enabled high cell productivity within a reduced cultivation period (9 days), while maintaining high viability (>90%), mesenchymal immunophenotype, and differentiation capacity. Distinct metabolic profiles were associated with enhanced proliferation, with increased glycolytic activity observed under optimized conditions. Despite these favorable outcomes, genotoxic analyses revealed a progressive, time-dependent accumulation of DNA damage and increased micronucleus frequency during expansion. Notably, these alterations did not impair cell proliferation, phenotype, or differentiation potential, indicating that conventional optimization metrics may not fully capture underlying genomic changes. Collectively, our findings demonstrate that bioprocess optimization based solely on classical performance parameters may overlook relevant biological alterations. By incorporating genotoxic endpoints into the evaluation framework, this study provides a refined approach for assessing large-scale stem cell expansion and contributes to improving the robustness and reliability of biomanufacturing strategies for therapeutic applications. Full article

Adipose-derived stem cells (ADSCs) are widely used in regenerative medicine and are considered key effectors underlying the therapeutic efficacy of autologous fat grafting for scarring and skin fibrosis, yet clinical outcomes remain variable. This review examines how obesity alters the adipose microenvironment through chronic inflammation and metabolic dysfunction, resulting in epigenetic changes, mitochondrial impairment, oxidative stress, and premature cellular senescence in ADSCs. ADSCs from obese individuals exhibit reduced stemness, impaired differentiation, and a pro-inflammatory secretome with diminished regenerative capacity. While weight loss may partially reverse these effects, persistent epigenetic and functional memory limits full recovery. This review argues that donor metabolic status is a determinant of ADSC therapeutic potency and discusses key challenges and opportunities for improving regenerative outcomes. Full article

Background: Apoptotic vesicles (ApoVs) derived from adipose stem cells (ASCs) have recently emerged as important mediators of tissue repair and are implicated in pathways relevant to hypertrophic scar (HS). Although ASCs exhibit potential in scar modulation, the therapeutic value of their apoptotic clearance products remains largely unexplored. Methods: In this study, we investigated the efficacy and mechanism of staurosporine (STS)-induced adipose stem cell derived apoptotic vesicles (ASCs-ApoVs) in mitigating HS. Western blot, RT-qPCR, and immunofluorescence were used to assess fibrotic markers including α-SMA, COL1A1, and COL3A1 and so on in hypertrophic scar derived fibroblasts (HS-fibroblasts). Results: ASCs-ApoVs significantly reduced profibrotic marker expression in HS-fibroblasts without short-term cytotoxicity. CDC20 down-regulation was identified as a critical target, through which ASCs-ApoVs suppressed Wnt/β-catenin signaling, as evidenced by the downregulation of β-catenin, c-MYC, Cyclin D1, and AXIN2. The efficacy of ASCs-ApoVs in hypertrophic scar regulation was also confirmed by the rabbit ear scar model. Furthermore, ASCs-ApoVs demonstrated notable structural and functional stability. Conclusions: In summary, our results established STS-induced ASCs-ApoVs as a potent multi-target strategy for hypertrophic scar regulation. Besides, the scalable production, functional stability, and favorable safety profile of ASCs-ApoVs underscore a strong promise for clinical translation. Full article

Objective: Effectively eliminating xenoimmunogenicity and achieving recellularization in cardiac xenografts remains a critical challenge in developing an ideal implantable xenograft. We have previously demonstrated that the removal of major antigens, including Galα1-3Gal (α-Gal) epitope and non-human sialic acid N-glycolylneuraminic acid (Neu5Gc), using α-galactosidase and peptide N-glycosidase F (PNGase-F), enables a synergistic effect with decellularization, significantly reducing the expression of carbohydrate-binding lectins without altering the biomechanical properties of the graft. The aim of this study was to establish an effective method for in vitro recellularization by seeding human mesenchymal stem cells (MSCs) on decellularized cardiac xenografts that had undergone optimal xenoantigen removal using α-galactosidase and PNGase-F. Additionally, this study aimed to evaluate the potential for in vivo recellularization. Methods: Decellularized porcine pericardium scaffolds treated with both enzymes were further modified by forming a fibrin mesh on their surface and within their structure, followed by the attachment of heparin and human vascular endothelial growth factor to the mesh. Subsequently, the scaffolds were seeded with human adipose tissue-derived stem cells for 8 weeks. In vitro recellularization, differentiation, and extracellular matrix remodeling of decellularized and enzyme-treated xenografts were assessed using vimentin, calponin, fibronectin, CD31, VWF, and phalloidin staining. To evaluate the potential for in vivo recellularization, decellularized glutaraldehyde-crosslinked xenografts with anticalcification treatments were seeded with rat bone marrow MSCs and implanted into rats subcutaneously to evaluate cell infiltration and calcification via histology, von Kossa staining, and micro-computed tomography. Results: In decellularized xenografts treated with both enzymes, stronger signals were detected and mesenchymal cell infiltration into the tissue was significantly faster, leading to accelerated recellularization. This recellularization process was more pronounced as time went on, with greater cell infiltration and evidence of cell differentiation. An in vivo study showed that decellularization and anticalcification treatments revealed stronger vimentin staining in histological analysis. The recellularization for our biocompatible scaffolds exhibited a lower degree of calcification compared to the non-recellularized tissue. Conclusions: We successfully developed major xenoantigen-free scaffolds by demonstrating the safety and synergistic effect of α-galactosidase and PNGase-F treatments and proved, for the first time, the effectiveness of recellularization using a human MSC monoculture on xenoantigen-free scaffolds. Furthermore, there was potential for in vivo recellularization of our biocompatible scaffolds seeded with MSCs. Full article