Search Results (83)

Diabetic nephropathy (DN) is the most common cause of kidney failure worldwide. Mesenchymal stromal cells (MSCs) have demonstrated promise for treating DN by promoting kidney repair and regulating inflammation. Allogeneic (Allo)-MSCs may have similar or superior anti-inflammatory effects to autologous (Auto)-MSCs but also have potential to elicit adverse immune responses due to major histocompatibility complex (MHC) mismatches. To better understand how MSC-delivered allo-antigens influence therapeutic effects of Allo-MSCs compared to Auto-MSCs in DN, lentiviral transduction was used to generate adipose-derived MSCs (ADSCs) from DBA/2J (H-2^d) mice which expressed an allogeneic class I MHC protein (H-2K^b). H-2K^b-ADSCs were injected intravenously into male DBA/2J mice at 11 and 13 weeks after initiation of diabetes, and their effects on renal functional and structural indices were compared at week 15 with those of diabetic DBA/2J recipients of vehicle alone or of empty vector-transduced DBA/2J ADSCs (EV-ADSCs). Both EV-ADSCs and H-2K^b-ADSCs resulted in reduced kidney/total body weight ratio, blood urea nitrogen (BUN), urine albumin creatinine ratio (uACR), mesangial matrix expansion (MME) and renal fibrosis compared to vehicle alone, without influencing glycemia or survival. However, H-2K^b-ADSCs recipients had greater reductions in BUN and uACR, reduced intra-renal myeloid cell infiltration, increased splenic regulatory T cell (Treg) proportions and increased intra-renal Treg infiltration and FOXP3 and IL-10 mRNA. Nonetheless, recipients of H-2K^b-ADSCs also had decreased splenic CD4/CD8 T cell ratios, increased circulating anti-H-2K^b IgG antibodies and histological and biochemical evidence of inflammatory liver injury. These novel findings demonstrated that ADSCs expressing an MHC-I allo-antigen had superior beneficial effects on DN than fully autologous ADSCs. Improved DN severity was associated with immune modulation, including Treg enhancement, but also had potentially detrimental immunological effects in mice with established diabetes. The results highlight the need for further investigation of the immune modulatory effects of Allo-MSCs in diabetes and its organ-specific complications. Full article

Small-diameter vascular grafts (SDVGs, ≤6 mm) face significant barriers in vascular reconstruction due to poor long-term patency stemming from thrombosis, intimal hyperplasia, and mechanical mismatch. Increasing rates of cardiovascular disease and limited autologous vessel supply underscore the urgent need for functional SDVGs. This review discusses the critical failure mechanisms of SDVGs and recent material-based advances—hydrophilic modifications, charge control, micro- and nano-engineering, antimicrobial and anti-inflammatory treatments, and controlled bioactive release (e.g., heparin, nitric oxide, t-PA). It details progress in cellular and tissue engineering for rapid endothelialization, smooth muscle regeneration, and mechanical durability. The review also highlights emerging gene engineering, the use of bioactive peptides, and molecular pathway strategies for physiological antithrombotic restoration. Finally, it outlines future directions, including smart materials, accelerated endothelialization, advanced manufacturing (3D printing, multilayer electrospinning), multifunctional composites, and clinical translation. Overall, SDVG research is shifting toward active, regenerative vascular substitutes with improved clinical prospects. Full article

Blood is a multitask, fluid tissue that is considered as an endless goldmine for regenerative therapies. This connective tissue carries myriad multidomain proteins as the workhorse of biological functions integrated in complex molecular networks. Among them, the coagulation system stands out, with platelets and plasma coagulation proteins playing multiple roles in clotting, defense and tissue repair, the latter of which is the final byproduct process stemming from the hemostatic–inflammatory, cell-reprogramming and inflammation resolution after a tissue injury. By mimicking coagulation and hemostasis but lacking inflammatory properties, platelet-rich plasma (PRP) is emerging as an innovative autologous therapy operating as a local delivery system of growth factors. Processing of the patient blood to manufacture PRP encompasses blood anticoagulation; blood deconstruction through centrifugation and fractionation; and activation of plasma, endowing the applied product with anti-inflammatory, trophic, antifibrotic and antialgic properties in a context-dependent manner. However, the field of PRPs faces controversies due to the heterogeneity of their biological compositions and modalities of application. Moreover, there are some drawbacks derived from patient age and some other conditions, all impinging negatively on PRP clinical outcomes. Standardization of the manufacturing process, elaboration of guidelines of application and use of allogenic PRPs are emerging as possible solutions to surmount these pitfalls. Full article

The ocular surface is a structure crucial to maintaining eye health and proper vision. Unfortunately, ocular surface diseases functioning as chronic epithelial defects, inflammation, impaired healing, require immediate regenerative repair treatment that can restore tissue integrity and function. Conventional therapies, such as artificial tears and topical anti-inflammatory agents, principally provide symptomatic relief without addressing the underlying biological deficits, thus leading to incomplete or delayed recovery. Therefore, blood derivatives have emerged as a promising bioactive therapy that not only lubricates but also actively promotes regeneration through the delivery of cytokines, growth factors, and vitamins naturally present in blood. Due to their properties mimicking the components of natural tears, autologous origin, biocompatibility and capacity to enhance tissue repair, they have emerged as a cornerstone in regenerative medicine. Therefore, the purpose of this review was to compare the evolution, positive aspects, and drawbacks, in order to demonstrate the molecular mechanism of action and the therapeutic efficacy of different blood derivates at treating ocular surface disease. Over time, these biologic preparations have evolved from the use of simple traditional serum-based derivatives to more advanced platelet-rich products, underscoring the evolving understanding of platelet-driven molecular and cellular mechanisms in tissue regeneration. Despite their widespread use, we would like to highlight the current limitations related to the lack of standardized preparation protocols, variability in composition, and evidence-based integration into clinical practice. Finally, this review highlights contemporary research trends and depicts future directions advancing the field. Key priorities include the establishment of standardized, reproducible preparation protocols; the development of next-generation platelet-derived concentrates and biomaterials; and the integration of multi-omics technologies to achieve comprehensive profiling of their biological and therapeutic activity. Moving toward methodological standardization and the execution of well-designed, high-quality comparative clinical trials will be essential to reinforce the scientific foundation, enhance translational potential, and ensure the clinical reliability of blood-derived therapies in modern regenerative medicine. 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

Background/Objectives: Dry eye disease (DED) is a prevalent, complex disorder with a major impact on patients’ quality of life. While artificial tears (AT) are still the first-line treatment, their effectiveness is often limited in moderate-to-severe cases. Autologous serum (AS) and platelet-rich plasma (PRP) are now recognized as viable biologic treatments due to their regenerative and anti-inflammatory characteristics. This systematic review and meta-analysis sought to assess and compare the clinical efficacy of PRP, AS, and AT in the treatment of DED, with a focus on comparative studies. Methods: A comprehensive search of PubMed, Scopus, and Google Scholar was conducted until June 2025 for studies directly comparing PRP, AS, and AT. Eligible trials included patients with DED who reported results such as the Schirmer test, tear break-up time (TBUT), and Ocular Surface Disease Index (OSDI). The risk of bias was calculated using ROB 2 for randomized trials and ROBINS-I for non-randomized studies. Meta-analyses were carried out using standardized mean differences (SMDs) and 95% confidence intervals (CIs). Results: Seventeen studies were included in the systematic review. Both PRP and AS demonstrated greater improvements in OSDI, TBUT, and Schirmer test scores compared to AT. PRP showed a trend toward better outcomes than AS, especially in studies using injectable PRP. However, substantial heterogeneity and methodological variability were noted. Conclusions: Comparative research suggests that PRP and AS are more effective than AT in treating DED. Direct comparisons of PRP and AS yield varied results, with the route of delivery impacting outcomes. Given the heterogeneity of current protocols, further standardized, long-term trials are required to confirm the optimal delivery method and ensure safety. 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

Background/Objectives: Dry eye disease (DED) is a multifactorial condition with complex pathophysiology involving tear film instability, ocular surface inflammation, and nerve dysfunction. This review summarizes current evidence on the different available therapies targeting these mechanisms. Methods: A review of clinical studies evaluating treatment outcomes for therapies targeting aqueous tear deficiency, Meibomian gland dysfunction, ocular surface inflammation, and ocular pain was conducted, with an emphasis on randomized controlled trials and meta-analyses where available. Results: Artificial tears provide symptomatic relief with limited impact on tear film stability. Punctal plugs improve tear retention but show variable efficacy across studies. Treatments targeting MGD—such as lipid-based lubricants, eyelid hygiene, thermal pulsation (LipiFlow, iLux), and intense pulsed light (IPL)—demonstrate improvements in gland function, though outcomes vary. Anti-inflammatory agents including cyclosporine, lifitegrast, and short-term corticosteroids improve ocular surface signs, with mixed symptom relief. Biologic therapies like autologous serum tears and platelet-rich plasma show promise for both signs and symptoms, but data remain inconsistent. Nerve-targeted therapies, including oral neuromodulators (gabapentin, antidepressants), botulinum toxin, and transcutaneous nerve stimulation, have shown potential for managing neuropathic ocular pain, although randomized data are limited. Overall, variability in study designs, patient populations, and outcome measures highlights the need for more rigorous research. Conclusions: Personalized, mechanism-based treatment strategies are essential for optimizing outcomes in DED. Future research should prioritize well-designed, controlled studies to clarify the role of emerging therapies and guide the individualized management of this heterogeneous condition. Full article

Background: Diabetic kidney disease (DKD) is a significant risk factor for End-Stage Renal Disease, with a high global incidence and mortality rate. Hyperglycemia in DKD induces inflammation, contributing to glomerular hyperfiltration, fibrosis, and impaired renal function. Current therapies, including SGLT2 inhibitors, ACE inhibitors, and ARBs, show limited efficacy. Autologous dendritic cells (DCs) offer potential anti-inflammatory effects by reducing cytokine activity and fibrosis biomarkers. Methods: A quasi-experimental pretest–post-test design was conducted involving 29 DKD patients. Baseline blood and urine samples were collected for MMP-9, TGF-β, and Doppler ultrasound (PSV, EDV) measurements. The subjects received subcutaneous injections of autologous DCs, and follow-up measurements were conducted four weeks after treatment. The statistical analyses included paired t-tests, Wilcoxon signed-rank tests, and linear regression. Results: After treatment, there were a significant decrease in PSV (from 47.1 ± 23.87 cm/s to 27.85 ± 20.53 cm/s, p = 0.044) and a significant increase in EDV (from 13 ± 5.32 cm/s to 15.7 ± 12.55 cm/s, p = 0.039). A strong correlation was observed between the TGF-β and MMP-9 levels (p = 0.001). Linear regression analysis showed reduced MMP-9 influence on the TGF-β after treatment, suggesting potential fibrosis reduction. Gender and UACR subgroup analyses revealed significant PSV and EDV improvements in females and the microalbuminuria group. Conclusion: Autologous dendritic cell therapy significantly improved renal hemodynamics and showed potential to reduce fibrosis by modulating TGF-β and MMP-9 levels in DKD patients, warranting further investigation. Full article

Injectable Platelet-Rich Fibrin (i-PRF) has emerged as a promising tool in regenerative medicine, particularly in orthopedics, due to its unique biological properties and ease of preparation. i-PRF is an autologous platelet concentrate derived through a simple, anticoagulant-free centrifugation process, resulting in a liquid matrix enriched with fibrin, leukocytes, and growth factors. These components promote tissue regeneration, angiogenesis, and anti-inflammatory responses, making i-PRF suitable for bone and cartilage repair as well as drug delivery systems. This review discusses the history, biological mechanisms, and clinical applications of i-PRF in orthopedics, highlighting its potential advantages over traditional platelet-rich plasma (PRP). Furthermore, we address the challenges and limitations of i-PRF, including drug stability, release control, and bioactive interactions, underscoring the need for further research to optimize its therapeutic efficacy. Full article

This review systematically examines the oral complications associated with conventional and novel anti-cancer therapies. It highlights that while molecularly targeted agents including monoclonal antibodies targeting the vascular endothelial growth factor and its receptor, the epidermal growth factor receptor, tyrosine kinase inhibitors, and immune checkpoint inhibitors tend to exhibit a lower overall toxicity profile compared to traditional cytotoxic chemotherapeutics, they are nonetheless linked to significant oral adverse events. These complications encompass inflammatory mucosal reactions known as mucositis, salivary gland dysfunction leading to a sensation of dryness in the mouth, taste alterations referred to as dysgeusia, and, critically, medication-related osteonecrosis of the jaw. In particular, bone-modifying agents such as bisphosphonates and denosumab disrupt bone remodeling and the formation of new blood vessels, thereby increasing the susceptibility to osteonecrosis of the jaw, especially following invasive dental procedures. The review delineates the multifactorial pathogenesis underlying these toxicities, which involves direct cell toxicity, impaired wound healing, and secondary infections. Furthermore, it emphasizes the importance of pre-treatment dental evaluation and preventive strategies including patient education, prophylactic dental care, and the integration of adjunctive therapies such as laser therapy and autologous platelet concentrates to mitigate these adverse effects. The analysis advocates for interdisciplinary collaboration between oncologists and dental professionals to optimize management protocols, enhance treatment adherence, and ultimately improve the quality of life for oncology patients undergoing anti-cancer therapy. 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

Systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myositis (IIM) are autoimmune diseases managed with long-term immunosuppressive therapies. Hu19-CD828Z, a fully human anti-CD19 chimeric antigen receptor (CAR) with a CD28 costimulatory domain, is engineered to potently deplete B-cells. In this study, we manufactured Hu19-CD828Z CAR T-cells from peripheral blood of SLE, IIM, and SSc patients and healthy donors (HDs). CAR-mediated, CD19-specific activity of these cells was evaluated in vitro by assessing cytotoxicity, cytokine release, and proliferation assays in response to autologous CD19⁺ B-cells, the CD19⁺ NALM-6 B-cell line, or a CD19⁻ U937 non-B-cell line as targets. The results demonstrated an increased proliferation of Hu19-CD828Z CAR T-cells and dose-dependent cytotoxicity against primary autologous and NALM-6 B-cells compared to non-transduced controls or co-cultures with non-B-cells. Notably, autoimmune-patient-derived CAR T-cells produced lower levels of inflammatory cytokines than healthy-donor-derived CAR T-cells in response to CD19⁺ B-cell targets. These data support the potential of Hu19-CD828Z and its therapeutic cell product KYV-101 as a therapeutic strategy to achieve deep B-cell depletion in SLE, IIM, and SSc patients, and highlights its promise for broader application in B-cell-driven autoimmune disorders. Full article

Type 2 diabetes mellitus (T2DM) is a global health concern, with diabetic neuropathy (DN) being a prevalent complication. Current DN treatments focus on blood glucose control and pain management, which show limited efficacy. This study explored the effects of autologous dendritic cell (DC) administration on improving DN symptoms. A quasi-experimental clinical trial was conducted on 28 DN patients at Gatot Soebroto Army Hospital. Patients received autologous DC administration, with their Toronto Clinical Neuropathy Score (TCNS), Transforming Growth Factor-β (TGF-β), and Vascular Cell Adhesion Molecule-1 (VCAM-1) levels measured before and at four weeks after treatment. The results show an average TCNS reduction from 8.93 to 7.5 (p < 0.001). TGF-β levels increased slightly from 41.16 ng/mL to 44.18 ng/mL (p > 0.05). VCAM-1 levels increased from 1389.75 ng/mL to 1403.85 ng/mL. Correlation analysis showed that TGF-β levels had a significant negative correlation with the TCNS (r = −0.353; p = 0.033) and VCAM-1 levels (r = −0.521; p = 0.002). Autologous DC administration significantly improves DN. While the changes in TGF-β and VCAM-1 levels were not statistically significant, their trends suggest that there was an anti-inflammatory effect. These findings highlight the potential of autologous DC therapy as a complementary approach to manage DN through inflammation reduction and nerve repair. Full article

Diabetic kidney disease (DKD) significantly increases mortality, with patients facing a fourfold risk of death within ten years. Chronic inflammation, marked by transforming growth factor-β (TGF-β) and intracellular adhesion molecule-1 (ICAM-1) activity, contributes to kidney damage and fibrosis. This study investigates the effect of autologous dendritic cells on inflammation and kidney function, focusing on apparent diffusion coefficient (ADC), TGF-β, and ICAM-1 levels. This quasi-experimental clinical trial involved 22 DKD patients at Gatot Soebroto Army Hospital. Patients received autologous dendritic cell injections. Baseline and post-intervention magnetic resonance imaging (MRI) scans measured ADC values, and ICAM-1 and TGF-β levels were analyzed. Post intervention, the median ADC decreased from 1.75 mm²/s to 1.64 mm²/s (p = 0.223). ICAM-1 levels increased significantly in females (p = 0.04) but not in males (p = 0.35). No significant changes were found in TGF-β levels (p = 0.506). ADC changes were statistically insignificant and did not correlate with CKD severity. ICAM-1 increases in females correlated with improved creatinine levels, suggesting kidney function improvement. Autologous dendritic cell therapy revealed potential gender-specific immune responses but showed limited overall biomarker improvements. Further studies are required to validate its therapeutic value. Full article