Search Results (32)

Hair loss disorders, particularly androgenetic alopecia (AGA), are common conditions that carry significant psychosocial impact. Current standard therapies, including minoxidil, finasteride, and hair transplantation, primarily slow progression or re-distribute existing follicles and do not regenerate lost follicular structures. In recent years, regenerative medicine has been associated with a gradual shift toward approaches that aim to restore follicular function and architecture. Stem cell-derived conditioned media and exosomes have shown the ability to activate Wnt/β-catenin signaling, enhance angiogenesis, modulate inflammation, and promote dermal papilla cell survival, resulting in improved hair density and shaft thickness with favorable safety profiles. Autologous cell-based therapies, including adipose-derived stem cells and dermal sheath cup cells, have demonstrated the potential to rescue miniaturized follicles, although durability and standardization remain challenges. Adjunctive interventions such as microneedling and platelet-rich plasma (PRP) further augment follicular regeneration by inducing controlled micro-injury and releasing growth and neurotrophic factors. In parallel, machine learning-based diagnostic tools and deep hair phenotyping offer improved severity scoring, treatment monitoring, and personalized therapeutic planning, while robotic Follicular Unit Excision (FUE) platforms enhance surgical precision and graft preservation. Advances in tissue engineering and 3D follicle organoid culture suggest progress toward producing transplantable follicle units, though large-scale clinical translation is still in early development. Collectively, these emerging biological and technological strategies indicate movement beyond symptomatic management toward more targeted, multimodal approaches. Future progress will depend on standardized protocols, regulatory clarity, and long-term clinical trials to define which regenerative approaches can reliably achieve sustainable follicle renewal in routine cosmetic dermatology practice. Full article

Craniofacial bone defects of critical size, caused by trauma, tumors, infections, or congenital maldevelopment, represent a major challenge in plastic and reconstructive surgery. Autologous bone grafting is considered the gold standard, but limitations such as donor site morbidity and limited availability have prompted the development of artificial bone tissue engineering scaffolds. In recent years, bioactive scaffolds have been increasingly utilized in favor of inert biomaterials due to their immunomodulation and osteoinduction capabilities. This review methodically summarizes loading strategies for the functionalization of scaffolds with bioactive components, including cell regulatory factors, drugs, ions, stem cells, exosomes, and components derived from human tissues or cells to promote bone regeneration. The following mechanisms are involved: (1) the polarization of macrophages (M1-M2 transition), (2) the dynamic regulation of bone metabolism, and (3) the coupling of osteogenesis and angiogenesis. This review focuses on innovative delivery systems, such as 3D-printed scaffolds, nanocomposites and so on, that enable spatiotemporal control of bioactive cargo release. These address key challenges, such as infection resistance, vascularization, and mechanical stability in the process of bone regeneration. In addition, the article discusses emerging technologies, including stem cells and exosome-based acellular therapies, which demonstrate potential for personalized bone regeneration. This review integrates immunology, materials science, and clinical needs, providing a roadmap for the design of next-generation bone tissue engineering scaffolds to overcome critical-sized bone defects. Full article

Androgenetic alopecia (AGA) is a prevalent, multifactorial hair disorder affecting a substantial portion of both males and females, with significant psychosocial consequences. Over the past decade, regenerative medicine has reshaped AGA treatment, offering biologically driven alternatives to conventional pharmacological and surgical therapies. Among these, Autologous Micrografting Technology (AMT) (Regenera Activa^® by Rigenera^® Technology, Barcelona, Spain) emerged 10 years ago as a notable innovation leveraging the body’s intrinsic regenerative potential through micrografts derived from a healthy scalp tissue. This review provides a comprehensive overview of the pathophysiology of AGA—including genetic, hormonal, and inflammatory contributors—and evaluates the clinical efficacy, safety, and mechanistic basis of AMT in comparison with other regenerative strategies such as platelet-rich plasma, adipose-derived mesenchymal stem cells, and exosome-based treatments. Clinical studies demonstrate that AMT yields significant short-term improvements in hair density and thickness with favorable safety outcomes. Moreover, advancements in device technology and treatment protocols have enhanced consistency and reproducibility. As multimodal and personalized approaches gain traction in hair restoration, AMT is a minimally invasive point-of-care procedure within the evolving regenerative landscape. Future studies are warranted to optimize treatment algorithms, extend follow-up data, better define patient selection criteria for maximizing outcomes with AMT, and expand the indication of autologous micrografting technology. Full article

Platelet-rich plasma (PRP) is an autologous blood-derived concentrate increasingly utilized in regenerative medicine for its ability to accelerate healing and tissue repair. PRP is broadly classified by leukocyte content, fibrin architecture, and platelet concentration, with classification systems developed to standardize characterization. Preparation methods, including single- or double-spin centrifugation and buffy coat techniques, influence the final composition of PRP, determining the relative proportions of platelets, leukocytes, plasma proteins, and extracellular vesicles. These components act synergistically, with platelets releasing growth factors (e.g., VEGF, PDGF, TGF-β) that stimulate angiogenesis and matrix synthesis, leukocytes providing immunomodulation, plasma proteins facilitating scaffolding, and exosomes regulating intercellular signaling. Mechanistically, PRP enhances tissue repair through four key pathways: platelet adhesion molecules promote hemostasis and cell recruitment; immunomodulation reduces pro-inflammatory cytokines and favors M2 macrophage polarization; angiogenesis supports vascular remodeling and nutrient delivery; and serotonin-mediated pathways contribute to analgesia. These processes establish a regenerative microenvironment that supports both structural repair and functional recovery. Clinically, PRP has been applied across multiple specialties. In orthopedics, it promotes tendon, cartilage, and bone healing in conditions such as tendinopathy and osteoarthritis. In dermatology, PRP enhances skin rejuvenation, scar remodeling, and hair restoration. Gynecology has adopted PRP for ovarian rejuvenation, endometrial repair, and vulvovaginal atrophy. In dentistry and oral surgery, PRP accelerates wound closure and osseointegration, while chronic wound care benefits from its angiogenic and anti-inflammatory effects. PRP has also favored gingival recession coverage, regeneration of intrabony periodontal defects, and sinus grafting. Although preparation heterogeneity remains a challenge, PRP offers a versatile, biologically active therapy with expanding clinical utility. Full article

Periodontal ligament stem cells (PDLSCs) represent a promising cell source for true periodontal regeneration due to their ability to form bone, cementum, and functional ligament. This review critically synthesised twelve in vivo studies (rats = 5, pigs = 2, dogs = 2, sheep = 2, one human trial) evaluating PDLSC transplantation for periodontal defects. A comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library (to May 2025) identified 358 records, of which 12 met predefined inclusion criteria. Data extraction encompassed cell source, scaffold, dose, follow-up, and quantitative regenerative outcomes. Nine studies reported cell doses (5 × 10⁵–2 × 10⁷ cells) and six PDLSC regeneration rates (33–100%). After normalisation for host mass, effective delivery ranged from 10⁵ to 10⁶ cells·kg⁻¹, with optimal outcomes typically above 10⁵ cells·kg⁻¹. PDLSC transplantation consistently enhanced alveolar bone, cementum, and periodontal-ligament regeneration compared with scaffold-alone or untreated controls, with the highest outcomes obtained using biocompatible scaffolds such as Hydroxyapatite/Tricalcium Phosphate (HA/TCP), Gelfoam, or amniotic membrane. Both autologous and allogeneic PDLSC achieved equivalent performance and excellent safety, while xenogeneic models confirmed immune tolerance. Despite encouraging results, the evidence remains preliminary—most studies were short-term and small-scale, and only one randomised human trial has been published. Standardisation of cell preparation, scaffold selection, dosing (absolute and mass-normalised), and follow-up is urgently needed. Future research should include Good Manufacturing Practice (GMP)-compliant clinical trials and mechanistic studies on PDLSC differentiation, paracrine signalling, and exosome-mediated effects to consolidate their translational potential for predictable periodontal regeneration. Full article

Over the past decade, cellular immunotherapy has emerged as a transformative strategy for non-small cell lung cancer (NSCLC), with dendritic-cell (DC) vaccines, T-cell vaccines, and natural killer (NK)-cell therapies demonstrating distinct mechanisms and clinical potential. DC vaccines capitalize on antigen presentation to prime tumor-specific T-cell responses, showing excellent safety profiles limited mainly to injection-site reactions and flu-like symptoms. While monotherapy has shown limited efficacy, combinations with checkpoint inhibitors or chemotherapy enhance immune activation and survival outcomes. Recent innovations, including neoantigen-loaded, mRNA-electroporated, and exosome-pulsed DCs, demonstrate improved immunogenicity and personalized approaches. T-cell vaccines, designed to activate cytotoxic CD8+ T-cell responses, have been tested across multiple platforms, including peptide-based (MAGE-A3), viral vector (TG4010/MUC1), and mRNA (CV9201/92) formulations. While the phase III MAGRIT trial presented no disease-free survival (DFS) benefit with adjuvant MAGE-A3 vaccination, the TG4010 vaccine improved progression-free survival (PFS; HR 0.66) and overall survival (OS; HR 0.67) in MUC1-positive NSCLC when combined with chemotherapy. Current strategies focus on personalized neoantigen vaccines and KRAS-targeted approaches (e.g., ELI-002), with ongoing phase III trials evaluating their potential in resectable NSCLC. NK-cell therapies have also shown promise, with early trials establishing the feasibility of autologous and allogeneic infusions, while engineered CAR-NK cells enhance tumor-specific targeting. Combination strategies with checkpoint inhibitors significantly improve response rates and PFS, revealing synergies between innate and adaptive immunity. Recent advances include cytokine-enhanced, memory-like NK cells to overcome immunosuppression and “off-the-shelf” products for broader clinical use. Together, these cellular immunotherapies represent a versatile and evolving frontier in NSCLC treatment, with ongoing research optimizing combinations, delivery platforms, and patient selection to maximize therapeutic benefit. Full article

Ovarian aging is characterized by a gradual decline in both reproductive and endocrine functions, ultimately culminating in the cessation of ovarian activity around the age of 50, when most women experience natural menopause. The decline begins early, as follicular attrition is initiated in utero and continues throughout childhood and reproductive life. Most follicles undergo atresia without progressing through substantial stages of growth. With increasing age, a pronounced reduction occurs in the population of resting follicles within the ovarian reserve, accompanied by a decline in the size of growing follicular cohorts. Around the age of 38, the rate of follicular depletion accelerates, sometimes resulting in diminished ovarian reserve (DOR). The subsequent menopausal transition involves complex, irregular hormonal dynamics, manifesting as increasingly erratic menstrual patterns, primarily driven by fluctuations in circulating estrogens and a rising incidence of anovulatory cycles. In parallel with the progressive depletion of the follicular pool, the serum concentrations of anti-Müllerian hormone (AMH) decline gradually, while reductions in inhibin B levels become more apparent during the late reproductive years. The concomitant decline in both inhibin B and estrogen levels leads to a compensatory rise in circulating follicle-stimulating hormone (FSH) concentrations. Together, these endocrine changes, alongside the eventual exhaustion of the follicular reserve, converge in the onset of menopause, which is defined by the absence of menstruation for twelve consecutive months. The mechanisms contributing to ovarian aging are complex and multifactorial, involving both the oocyte and the somatic cells within the follicular microenvironment. Oxidative stress is thought to play a central role in the age-related decline in oocyte quality, primarily through its harmful effects on mitochondrial DNA integrity and broader aspects of cellular function. Although granulosa cells appear to be relatively more resilient, they are not exempt from age-associated damage, which may impair their hormonal activity and, given their close functional relationship with the oocyte, negatively influence oocyte competence. In addition, histological changes in the ovarian stroma, such as fibrosis and heightened inflammatory responses, are believed to further contribute to the progressive deterioration of ovarian function. A deeper understanding of the biological processes driving ovarian aging has facilitated the development of experimental interventions aimed at extending ovarian functionality. Among these are the autologous transfer of mitochondria and stem cell-based therapies, including the use of exosome-producing cells. Additional approaches involve targeting longevity pathways, such as those modulated by caloric restriction, or employing pharmacological agents with geroprotective properties. While these strategies are supported by compelling experimental data, robust clinical evidence in humans remains limited. Full article

The low predictability of the effects of autologous platelet-rich plasma (PRP) in regenerative therapy for patients with type 1 and type 2 diabetes mellitus (DM) underscores the need for further research assessing the reparative effects of PRP based on the type of DM. The aim of this study was to evaluate the regenerative potential of PRP from young donors (30–40 years old) with DM1 and DM2 in vitro, specifically its effects on human dermal fibroblast cell culture. The in vitro effects of PRP from patients with type 1 and type 2 DM were investigated using a culture of human dermal fibroblasts (hTERT-HDFa) to evaluate metabolic activity, migration, proliferation of the cells, and their ability to release growth factors and exosomes. The study of the biological effects of PRP from donors with DM on hTERT-HDFa revealed a decrease in proliferative effects, an increase in prooxidant action, and toxic influences of PRP from patients, characterized by reduced metabolic activity and cell viability in culture, along with an increase in the percentage of necrosis. These effects were most pronounced in type 1 DM. The secretory response of hTERT-HDFa upon stimulation with PRP varied depending on the type of DM. Correlations indicated the differing significance of PAI-1, TGFB-1, PDGF, VEGF, and IL-6 in assessing the reparative potential across different types of DM. 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

The serine protease prostasin on the surface of the exosomes released from epithelial cells can interact with ectopically over-expressed cell-surface serine protease matriptase in cancerous B cells to initiate the prostasin–matriptase proteolytic activation cascade. Matriptase activation and the ensuing self-activation result in its removal from cancer cells, reducing cell proliferation and migration. In this study, we tested the hypothesis that the matriptase in the lymphoid cells could be removed by the prostasin-initiated activation and self-activation using genetically engineered autologous cells carrying prostasin. In co-cultures with the prostasin-positive cells, the matriptase on the prostasin-negative vector-control cells was removed in a dose-dependent manner, as determined by flow cytometry. This paracrine phenotype requires the active sites of both proteases. In silico analysis of the RNA-seq profiles indicated an imbalanced expression of high matriptase and low prostasin, and their cognate protease inhibitors in B-cell lymphoma patient specimens. The impact of exosomal prostasin on the cluster of differentiation molecules in activated human peripheral blood mononuclear cells was investigated by flow cytometry, revealing candidate mechanisms for prostasin’s role in regulating cellular adaptive immunity. This autologous paracrine prostasin–matriptase interaction could be exploited as a method for targeting over-expressed matriptase in diseases such as B-cell lymphoma. Full article

The skin functions as the body’s primary defense barrier; when compromised, it can lead to dehydration, infection, shock, or potentially life-threatening conditions. Miniature pigs exhibit skin characteristics and healing processes highly analogous to humans. Mesenchymal stem cells contribute to skin injury repair through a paracrine mechanism involving exosomes. This research examines whether adipose-derived MSC exosomes effectively enhance healing following autologous skin grafting in miniature pigs. It also compares the roles and distinctions of ADSCs and ADSC-Exos in inflammatory responses and tissue regeneration. This study found significantly reduced levels of oxidative stress products and pro-inflammatory factors, while antioxidant factors, anti-inflammatory factors, and pro-regenerative factors were elevated, and anti-regenerative factor levels decreased. Moreover, the expression levels of key markers—namely, PI3K, Akt, and mTOR—in the regeneration-associated signaling pathway were increased. The alterations in these indicators indicate that ADSC-Exos can regulate inflammatory responses and promote regeneration. This study provides a novel theoretical foundation for the implementation of acellular therapy in clinical settings. Full article

Autologous platelet-rich plasma (PRP) preparations are prepared at the point of care. Centrifugation cellular density separation sequesters a fresh unit of blood into three main fractions: a platelet-poor plasma (PPP) fraction, a stratum rich in platelets (platelet concentrate), and variable leukocyte bioformulation and erythrocyte fractions. The employment of autologous platelet concentrates facilitates the biological potential to accelerate and support numerous cellular activities that can lead to tissue repair, tissue regeneration, wound healing, and, ultimately, functional and structural repair. Normally, after PRP preparation, the PPP fraction is discarded. One of the less well-known but equally important features of PPP is that particular growth factors (GFs) are not abundantly present in PRP, as they reside outside of the platelet alpha granules. Precisely, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are mainly present in the PPP fraction. In addition to their roles as angiogenesis activators, these plasma-based GFs are also known to inhibit inflammation and fibrosis, and they promote keratinocyte migration and support tissue repair and wound healing. Additionally, PPP is known for the presence of exosomes and other macrovesicles, exerting cell–cell communication and cell signaling. Newly developed ultrafiltration technologies incorporate PPP processing methods by eliminating, in a fast and efficient manner, plasma water, cytokines, molecules, and plasma proteins with a molecular mass (weight) less than the pore size of the fibers. Consequently, a viable and viscous protein concentrate of functional total proteins, like fibrinogen, albumin, and alpha-2-macroglobulin is created. Consolidating a small volume of high platelet concentrate with a small volume of highly concentrated protein-rich PPP creates a protein-rich, platelet-rich plasma (PR-PRP) biological preparation. After the activation of proteins, mainly fibrinogen, the PR-PRP matrix retains and facilitates interactions between invading resident cells, like macrophages, fibroblast, and mesenchymal stem cells (MSCs), as well as the embedded concentrated PRP cells and molecules. The administered PR-PRP biologic will ultimately undergo fibrinolysis, leading to a sustained release of concentrated cells and molecules that have been retained in the PR-PRP matrix until the matrix is dissolved. We will discuss the unique biological and tissue reparative and regenerative properties of the PR-PRP matrix. Full article

Type 1 diabetes mellitus (T1DM) is a metabolic disorder characterized by hyperglycemia due to insulin insufficiency as a consequence of the pancreatic β-cells’ auto-immune attack. Nowadays, the application of mesenchymal stem cell-derived exosomes (MSCs-Exs) as the main cell-free therapy for diabetes treatment is becoming more and more extensive. In non-autologous therapy, researchers are moving towards a new strategy based on loading MSC-Exs with certain drugs, aimed at maintaining and maximizing the function of exosomes at the function site and enhancing their efficiency and safety. This study aims to explore and compare the therapeutic potentialities of mesenchymal stem cell-derived exosomes (MSCs-Exs) loaded with either selenium (Se) or nano selenium (NSe), a natural antioxidant micronutrient, in the management of T1DM in rats. In our 4-week experiment, six rat groups were included, namely, control, Ex+Se, Ex+NSe, STZ-diabetic (D), D+ Ex+Se, and D+Ex+NSe groups. Both diabetic-treated groups showed marked pancreatic regenerative antioxidant, immunomodulatory, anti-inflammatory, and anti-apoptotic capacities, with the D+Ex+NSe injection showing superiority in managing diabetes hazards, as evidenced by various biochemical and histological assessments. Full article

Lipofilling is an option for breast reconstruction after tumor resection to avoid the complications of an implant-based reconstruction. Although some concerns exist regarding the oncological safety of tissue rich in mesenchymal stem cells with their proangiogenic and proliferation-supportive properties, there are also reports that adipose-tissue-derived stem cells can exhibit antitumoral properties. We isolated primary adipose-tissue-derived stem cells. Both conditioned medium and exosomes were harvested from the cell culture and used to treat the breast cancer cell line MCF-7. Cell viability, cytotoxicity, and gene expression of MCF-7 cells in response to the indirect co-culture were evaluated. MCF-7 cells incubated with exosomes from adipose-tissue-derived stem cells show reduced cell viability in comparison to MCF-7 cells incubated with adipose-tissue-derived stem-cell-conditioned medium. Expression of proapoptotic genes was upregulated, and expression of antiapoptotic genes was downregulated. The debate about the oncological safety of autologous fat grafting after tumor resection continues. Here, we show that exosomes from adipose-tissue-derived stem cells exhibit some antitumoral properties on breast cancer cell line MCF-7. Full article

Burn injuries are a significant global health concern, leading to high morbidity and mortality. Deep burn injuries often result in delayed healing and scar formation, necessitating effective treatment options. Regenerative medicine, particularly cell therapy using adipose-derived stem cells (ASCs), has emerged as a promising approach to improving burn wound healing and reducing scarring. Both in vitro and preclinical studies have demonstrated the efficacy of ASCs and the stromal vascular fraction (SVF) in addressing burn wounds. The application of ASCs for burn healing has been studied in various forms, including autologous or allogeneic cells delivered in suspension or within scaffolds in animal burn models. Additionally, ASC-derived non-cellular components, such as conditioned media or exosomes have shown promise. Injection of ASCs and SVF at burn sites have been demonstrated to enhance wound healing by reducing inflammation and promoting angiogenesis, epithelialization, and granulation tissue formation through their paracrine secretome. This review discusses the applications of adipose tissue derivatives in burn injury treatment, encompassing ASC transplantation, as well as the utilization of non-cellular components utilization for therapeutic benefits. The application of ASCs in burn healing in the future will require addressing donor variability, safety, and efficacy for successful clinical application. Full article