Immunoradiation Therapy for End-Stage Undifferentiated Cervical Cancer That Restored Sensitivity to Chemotherapy and Resulted in the Disappearance of the Cancer.

Among cervical cancers, small cell undifferentiated carcinoma is rare. Because of its rapid progression, the prognosis is extremely poor. During the course of cisplatin-based chemotherapy for stage Ⅳ small cell undifferentiated carcinoma of the cervix, the patient developed drug resistance, and standard treatment was no longer feasible. Therefore, immunoradiotherapy was administered to activate anticancer immunity. Surprisingly, the cancer drug sensitivity was restored, and cisplatin was again successful, and the cancer disappeared. In addition, the activation of cancer-specific immunity maintained the disappearance of the cancer. It should be noted that immunoradiotherapy not only increases anti-cancer immunity but may also contribute to overcoming cancer drug resistance.

Evaluating the efficacy and safety of platelet-rich plasma injection for erectile dysfunction: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Platelet-rich plasma (PRP) is rich in factors that play a role in stem cell recruitment, inflammation modulation, and angiogenesis. With numerous preclinical and clinical studies exploring PRP as a potential treatment for erectile dysfunction (ED), this study focused on assessing the effectiveness of intracorporeal PRP injection for ED patients based on randomized controlled trials (RCTs). OBJECTIVES: The study sought to evaluate the efficacy and safety of intracorporeal injection of PRP in treating ED through a systematic review and meta-analysis of RCTs. METHODS: This study adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search was conducted on online databases (PubMed, Scopus, and ScienceDirect) to identify RCTs comparing PRP with a placebo for ED treatment. The primary outcomes assessed were the proportion of patients achieving the minimal clinically important difference in the International Index of Erectile Function (IIEF) domain and the change in the IIEF domain from baseline. The results were combined as a standardized mean difference between the PRP and placebo groups. RESULTS: Three RCTs comprising 230 patients were included. The overall effect favored PRP over placebo: total patients attaining minimal clinically important difference in the IIEF domain (odds ratio [OR], 5.64; 95% confidence interval [CI], 2.05 to 15.55; P = .0008), IIEF change from baseline (mean difference [MD], 2.99; 95% CI, 1.74 to 4.24; P = .00001), PSV (MD, 9.34; 95% CI, 0.84 to 17.84; P = .03), end-diastolic volume (standardized MD, 0.50; 95% CI, 0.17 to 0.83; P = .003), Sexual Encounter Profile question 3 (standardized MD, 0.78; 95% CI, 0.45 to 1.12; P = .00001), and visual analog scale score (MD, -0.30; 95% CI, -0.53 to -0.08; P = .008). CONCLUSION: PRP appears to be a safe and effective treatment for mild-to-moderate ED. However, further support from high-quality RCTs is needed to strengthen these findings.

Food Safety Assessment and Nutraceutical Outcomes of Dairy By-Products: Ovine Milk Whey as Wound Repair Enhancer on Injured Human Primary Gingival Fibroblasts.

The valorization of milk whey appears to be a promising strategy for managing by-products from dairy food industries, which incur demanding economic costs for treatment and/or disposal. Thanks to its numerous bioactive components, whey is expected to be increasingly incorporated into foods in the future. We investigated the safety of ovine milk whey through in vitro experiments on human primary gingival fibroblast (HGF-1) proliferation and wound healing. Fibroblasts play a crucial role in the repair processes from the late inflammatory phase until the final stages. Cells treated with varying concentrations of ovine whey (0.01%, 0.1%, 1%, and 10%) were able to close wounds more rapidly than vehicle-treated cells. Time- and dose-dependent responses were observed in cell populations exposed to ovine whey. Specifically, wounds treated with 0.1% and 10% milk whey showed better migratory capabilities compared to those treated with 0.01% and 1% milk whey after 24 and 48 h. In addition, ovine milk whey stimulates extracellular matrix deposition, as evidenced by the increasing levels of CD44 antigen density evaluated through FACS analysis, as well as COL1A1 expression measured both via RT-qPCR and immunofluorescence. This phenomenon was particularly evident at concentrations of 0.01% and 10%. Ensuring quality and safety has become a major concern for health authorities in the food industry. Our findings suggest that ovine milk whey is safe and possesses regenerative properties. It facilitates tissue re-establishment following exposure to environmental stress, particularly accelerating gingival wound closure.

Pre-clinical evaluation of the efficacy and safety of human induced pluripotent stem cell-derived cardiomyocyte patch.

BACKGROUND: Cell- or tissue-based regenerative therapy is an attractive approach to treat heart failure. A tissue patch that can safely and effectively repair damaged heart muscle would greatly improve outcomes for patients with heart failure. In this study, we conducted a preclinical proof-of-concept analysis of the efficacy and safety of clinical-grade human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches. METHODS: A clinical-grade hiPSC line was established using peripheral blood mononuclear cells from a healthy volunteer that was homozygous for human leukocyte antigens. The hiPSCs were differentiated into cardiomyocytes. The obtained hiPSC-CMs were cultured on temperature-responsive culture dishes for patch fabrication. The cellular characteristics, safety, and efficacy of hiPSCs, hiPSC-CMs, and hiPSC-CM patches were analyzed. RESULTS: The hiPSC-CMs expressed cardiomyocyte-specific genes and proteins, and electrophysiological analyses revealed that hiPSC-CMs exhibit similar properties to human primary myocardial cells. In vitro and in vivo safety studies indicated that tumorigenic cells were absent. Moreover, whole-genome and exome sequencing revealed no genomic mutations. General toxicity tests also showed no adverse events posttransplantation. A porcine model of myocardial infarction demonstrated significantly improved cardiac function and angiogenesis in response to cytokine secretion from hiPSC-CM patches. No lethal arrhythmias were observed. CONCLUSIONS: hiPSC-CM patches are promising for future translational research and may have clinical application potential for the treatment of heart failure.

Regenerative Therapy for Corneal Scarring Disorders.

The cornea is a transparent and vitally multifaceted component of the eye, playing a pivotal role in vision and ocular health. It has primary refractive and protective functions. Typical corneal dysfunctions include opacities and deformities that result from injuries, infections, or other medical conditions. These can significantly impair vision. The conventional challenges in managing corneal ailments include the limited regenerative capacity (except corneal epithelium), immune response after donor tissue transplantation, a risk of long-term graft rejection, and the global shortage of transplantable donor materials. This review delves into the intricate composition of the cornea, the landscape of corneal regeneration, and the multifaceted repercussions of scar-related pathologies. It will elucidate the etiology and types of dysfunctions, assess current treatments and their limitations, and explore the potential of regenerative therapy that has emerged in both in vivo and clinical trials. This review will shed light on existing gaps in corneal disorder management and discuss the feasibility and challenges of advancing regenerative therapies for corneal stromal scarring.

Enhancing Quality of Life and Sexual Functioning in Female Androgenetic Alopecia: Therapeutic Potential of Hair Follicle-Derived Stem Cells.

BACKGROUND: The study aimed to examine the impact of stem cell treatment on quality of life (QoL) and sexual functioning in women with androgenetic alopecia (AGA). METHODS: Twenty-three women underwent a single session of autologous cellular micrografts (ACMs). The World Health Organization Quality of Life Brief Version (WHOQOL-BREF) and Female Sexual Function Index (FSFI) were used before and after 6 months. RESULTS: The AGA severity decreased by an average of 1 point on the Ludwig scale (p = 0.004) after treatment. FSFI scores indicated sexual dysfunction in over half of the women at baseline, but they improved significantly post-treatment for arousal [median (IQR): 4.8 (1.5) vs. 5.10 (0.9); p = 0.035] and satisfaction [4.4 (1.4) vs. 4.8 (1.8); p = 0.025]. QoL scores improved after treatment in psychological health (57.96 ± 19.0 vs. 69.35 ± 14.0; p = 0.031) and environment (72.96 ± 13.4 vs. 81.09 ± 12.6; p = 0.007), but not in physical health and social relationships. No associations were found between the WHOQOL-BREF or FSFI domains versus age and AGA severity. CONCLUSIONS: AGA reduces QoL and impacts sexual functioning in women with AGA. The high treatment burden arises from the chronic and progressive nature of AGA, coupled with limited treatment effectiveness. Effective treatments for AGA, like ACM, are urgently needed to enhance patient-reported outcomes along with clinical results.

Investigational regenerative medicine for non-traumatic osteonecrosis of the femoral head: a survey of registered clinical trials.

INTRODUCTION: Osteonecrosis of the femoral head (ONFH) is a refractory disease requiring joint replacement in young patients. Regenerative therapies have been developed. AREAS COVERED: This study surveyed clinical trials on regenerative medicine for ONFH. We extracted clinical trials on non-traumatic ONFH from the websites of five publicly available major registries (EuropeanUnion Clinical Trials Register ([EU-CTR],ClinicalTrials.gov, Chinese ClinicalTrial Registry [ChiCTR], University Hospital Medical InformationNetwork - Clinical Trial Registry [UMIN-CTR] and Australian New Zealand Clinical Trials Registry [ANZCTR]).The trials were classified into six categories based on purpose: surgical treatment, non-drug conservative treatment, conservative drug treatment, therapeutic strategy, diagnosis and pathogenesis, and regenerative therapy.) We extracted 169 clinical trials on ONFH. Of these, 37 were on regenerative medicine, including 29 on cell therapy. Surgical treatment was the most common treatment, followed by regenerative therapy.There were 9 clinical trials registered in the EU-CTR, with 5 on regenerative medicine; 79 trials registered on ClinicalTrials.gov, with 24 on regenerativemedicine; 54 trials registered in the ChiCTR, with 6 on regenerative medicine. EXPERT OPINION: The focus of the joint-preserving surgery has shifted to regenerative therapy based on using cell therapy in early-stage ONFH. The global standardisation of regenerative therapy is still ongoing.

Periodontal tissue regeneration with cementogenesis after application of brain-derived neurotrophic factor in 3-wall inflamed intra-bony defect.

OBJECTIVE: The purpose of this study is to investigate regenerative process by immunohistochemical analysis and evaluate periodontal tissue regeneration following a topical application of BDNF to inflamed 3-wall intra-bony defects. BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a role in the survival and differentiation of central and peripheral neurons. BDNF can regulate the functions of non-neural cells, osteoblasts, periodontal ligament cells, endothelial cells, as well as neural cells. Our previous study showed that a topical application of BDNF enhances periodontal tissue regeneration in experimental periodontal defects of dog and that BDNF stimulates the expression of bone (cementum)-related proteins and proliferation of human periodontal ligament cells. METHODS: Six weeks after extraction of mandibular first and third premolars, 3-wall intra-bony defects were created in mandibular second and fourth premolars of beagle dogs. Impression material was placed in all of the artificial defects to induce inflammation. Two weeks after the first operation, BDNF (25 and 50 µg/mL) immersed into atelocollagen sponge was applied to the defects. As a control, only atelocollagen sponge immersed in saline was applied. Two and four weeks after the BDNF application, morphometric analysis was performed. Localizations of osteopontin (OPN) and proliferating cell nuclear antigen (PCNA)-positive cells were evaluated by immunohistochemical analysis. RESULTS: Two weeks after application of BDNF, periodontal tissue was partially regenerated. Immunohistochemical analyses revealed that cells on the denuded root surface were positive with OPN and PCNA. PCNA-positive cells were also detected in the soft connective tissue of regenerating periodontal tissue. Four weeks after application of BDNF, the periodontal defects were regenerated with cementum, periodontal ligament, and alveolar bone. Along the root surface, abundant OPN-positive cells were observed. Morphometric analyses revealed that percentage of new cementum length and percentage of new bone area of experimental groups were higher than control group and dose-dependently increased. CONCLUSION: These findings suggest that BDNF could induce cementum regeneration in early regenerative phase by stimulating proliferation of periodontal ligament cells and differentiation into periodontal tissue cells, resulting in enhancement of periodontal tissue regeneration in inflamed 3-wall intra-bony defects.

Current developments and opportunities of pluripotent stem cells-based therapies for salivary gland hypofunction.

Salivary gland hypofunction (SGH) caused by systemic disease, drugs, aging, and radiotherapy for head and neck cancer can cause dry mouth, which increases the risk of disorders such as periodontitis, taste disorders, pain and burning sensations in the mouth, dental caries, and dramatically reduces the quality of life of patients. To date, the treatment of SGH is still aimed at relieving patients' clinical symptoms and improving their quality of life, and is not able to repair and regenerate the damaged salivary glands. Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and extended pluripotent stem cells (EPSCs), are an emerging source of cellular therapies that are capable of unlimited proliferation and differentiation into cells of all three germ layers. In recent years, the immunomodulatory and tissue regenerative effects of PSCs, their derived cells, and paracrine products of these cells have received increasing attention and have demonstrated promising therapeutic effects in some preclinical studies targeting SGH. This review outlined the etiologies and available treatments for SGH. The existing efficacy and potential role of PSCs, their derived cells and paracrine products of these cells for SGH are summarized, with a focus on PSC-derived salivary gland stem/progenitor cells (SGS/PCs) and PSC-derived mesenchymal stem cells (MSCs). In this Review, we provide a conceptual outline of our current understanding of PSCs-based therapy and its importance in SGH treatment, which may inform and serve the design of future studies.

Pluripotent stem cell-based cardiac regenerative therapy for heart failure.

Cardiac regenerative therapy using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is expected to become an alternative to heart transplantation for severe heart failure. It is now possible to produce large numbers of human pluripotent stem cells (hPSCs) and eliminate non-cardiomyocytes, including residual undifferentiated hPSCs, which can cause teratoma formation after transplantation. There are two main strategies for transplanting hPSC-CMs: injection of hPSC-CMs into the myocardium from the epicardial side, and implantation of hPSC-CM patches or engineered heart tissues onto the epicardium. Transplantation of hPSC-CMs into the myocardium of large animals in a myocardial infarction model improved cardiac function. The engrafted hPSC-CMs matured, and microvessels derived from the host entered the graft abundantly. Furthermore, as less invasive methods using catheters, injection into the coronary artery and injection into the myocardium from the endocardium side have recently been investigated. Since transplantation of hPSC-CMs alone has a low engraftment rate, various methods such as transplantation with the extracellular matrix or non-cardiomyocytes and aggregation of hPSC-CMs have been developed. Post-transplant arrhythmias, imaging of engrafted hPSC-CMs, and immune rejection are the remaining major issues, and research is being conducted to address them. The clinical application of cardiac regenerative therapy using hPSC-CMs has just begun and is expected to spread widely if its safety and efficacy are proven in the near future.

Protecting the regenerative environment: selecting the optimal delivery vehicle for cartilage repair-a narrative review.

Focal cartilage defects are common in youth and older adults, cause significant morbidity and constitute a major risk factor for developing osteoarthritis (OA). OA is the most common musculoskeletal (MSK) disease worldwide, resulting in pain, stiffness, loss of function, and is currently irreversible. Research into the optimal regenerative approach and methods in the setting of either focal cartilage defects and/or OA holds to the ideal of resolving both diseases. The two fundamentals required for cartilage regenerative treatment are 1) the biological element contributing to the regeneration (e.g., direct application of stem cells, or of an exogenous secretome), and 2) the vehicle by which the biological element is suspended and delivered. The vehicle provides support to the regenerative process by providing a protective environment, a structure that allows cell adherence and migration, and a source of growth and regenerative factors that can activate and sustain regeneration. Models of cartilage diseases include osteochondral defect (OCD) (which usually involve one focal lesion), or OA (which involves a more diffuse articular cartilage loss). Given the differing nature of these models, the optimal regenerative strategy to treat different cartilage diseases may not be universal. This could potentially impact the translatability of a successful approach in one condition to that of the other. An analogy would be the repair of a pothole (OCD) versus repaving the entire road (OA). In this narrative review, we explore the existing literature evaluating cartilage regeneration approaches for OCD and OA in animal then in human studies and the vehicles used for each of these two conditions. We then highlight strengths and challenges faced by the different approaches presented and discuss what might constitute the optimal cartilage regenerative delivery vehicle for clinical cartilage regeneration.

Characterization of platelet rich plasma in feline immunodeficiency virus-infected cats: Cell, and PDGF-BB and TGF-ß1 growth factor analysis.

Autologous platelet-rich plasma (PRP) contains growth factors (GFs) that modulate the expression of inflammatory cells; thus, these products could be considered a good strategy to favor tissue regeneration in feline immunodeficiency (FIV) positive cats. However, there is no scientific documentation on obtaining PRP in FIV-positive cats. Authors hypothesized that PRP can be obtained in FIV cats following the PRGF®-Endoret® methodology. The objectives of this study were to compare the platelet, erythrocyte, and leukocyte concentration between whole blood (WB) and the PRP; and determine the concentration of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor ß1 (TGF-ß1) in FIV-positive cats. Sixteen adults FIV-positive asymptomatic cats were included in the study. WB samples were drawn and the PRP was obtained by centrifugation at 265g for 10 min. Erythrocyte and leukocyte, platelets, and mean platelet volume (MPV) were determined both in WB and in PRP. PDGF-BB and TGF-ß1 concentrations were additionally determined in PRP. Platelet concentration increased 1.1 times in PRP fraction compared to WB, but no significant differences were reported. MPV was statistically higher in WB than in PRP (p = 0.001). Erythrocytes and leukocytes counts were decreased by 99% and 92%, respectively in the PRP fraction (p < 0.001). Regarding TGF-ß1, a higher concentration was shown in the PRP (p < 0.02). Although the product obtained could not be classified as PRP according to the PRGF®-Endoret® methodology, based on the drastic reduction of RBC and WBC, the PLT concentrate is of high purity.

Mitochondria in Mesenchymal Stem Cells: Key to Fate Determination and Therapeutic Potential.

Mesenchymal stem cells (MSCs) have become popular tool cells in the field of transformation and regenerative medicine due to their function of cell rescue and cell replacement. The dynamically changing mitochondria serve as an energy metabolism factory and signal transduction platform, adapting to different cell states and maintaining normal cell activities. Therefore, a clear understanding of the regulatory mechanism of mitochondria in MSCs is profit for more efficient clinical transformation of stem cells. This review highlights the cutting-edge knowledge regarding mitochondrial biology from the following aspects: mitochondrial morphological dynamics, energy metabolism and signal transduction. The manuscript mainly focuses on mitochondrial mechanistic insights in the whole life course of MSCs, as well as the potential roles played by mitochondria in MSCs treatment of transplantation, for seeking pivotal targets of stem cell fate regulation and stem cell therapy.

Oxygen generating biomaterials at the forefront of regenerative medicine: advances in bone regeneration.

Globally, an annual count of more than two million bone transplants is conducted, with conventional treatments, including metallic implants and bone grafts, exhibiting certain limitations. In recent years, there have been significant advancements in the field of bone regeneration. Oxygen tension regulates cellular behavior, which in turn affects tissue regeneration through metabolic programming. Biomaterials with oxygen release capabilities enhance therapeutic effectiveness and reduce tissue damage from hypoxia. However, precise control over oxygen release is a significant technical challenge, despite its potential to support cellular viability and differentiation. The matrices often used to repair large-size bone defects do not supply enough oxygen to the stem cells being used in the regeneration process. Hypoxia-induced necrosis primarily occurs in the central regions of large matrices due to inadequate provision of oxygen and nutrients by the surrounding vasculature of the host tissues. Oxygen generating biomaterials (OGBs) are becoming increasingly significant in enhancing our capacity to facilitate the bone regeneration, thereby addressing the challenges posed by hypoxia or inadequate vascularization. Herein, we discussed the key role of oxygen in bone regeneration, various oxygen source materials and their mechanism of oxygen release, the fabrication techniques employed for oxygen-releasing matrices, and novel emerging approaches for oxygen delivery that hold promise for their potential application in the field of bone regeneration.

Label-free enrichment of human pluripotent stem cell-derived early retinal progenitor cells for cell-based regenerative therapies.

Pluripotent stem cell-based therapy for retinal degenerative diseases is a promising approach to restoring visual function. A clinical study using retinal organoid (RO) sheets was recently conducted in patients with retinitis pigmentosa. However, the graft preparation currently requires advanced skills to identify and excise suitable segments from the transplantable area of the limited number of suitable ROs. This remains a challenge for consistent clinical implementations. Herein, we enabled the enrichment of wild-type (non-reporter) retinal progenitor cells (RPCs) from dissociated ROs using a label-free ghost cytometry (LF-GC)-based sorting system, where a machine-based classifier was trained in advance with another RPC reporter line. The sorted cells reproducibly formed retinal spheroids large enough for transplantation and developed mature photoreceptors in the retinal degeneration rats. This method of enriching early RPCs with no specific surface antigens and without any reporters or chemical labeling is promising for robust preparation of graft tissues during cell-based therapy.

Stem Cell-Based Tissue Engineering Approaches for Diabetic Foot Ulcer: a Review from Mechanism to Clinical Trial.

Diabetic foot ulcer (DFU) is a complication from incomplete or prolonged wound healing, at times requires amputation, putting substantial health and socioeconomic burden. Wound healing is a dynamic overlapping process that can be regulated by arrays of molecular factors showing redundancy in function. However, dysregulation in the mechanism of angiogenesis, extra cellular matrix (ECM) formation and immune modulation are the major causes for impair wound healing in hyperglycaemic patients. Despite development of wound care research, there is a lack of well-accepted targeted therapy with multidisciplinary approach for DFU treatment. Stem cell therapy holds a promising outcome both in preclinical and clinical trials because of its ability to promote healing via regeneration and specialized tissue differentiation. Among different types of stem cells, regenerative potential of mesenchymal stem cell (MSC) is well demonstrated in both experimental and clinical trial. Still there is a huge knowledge gap among medical practitioners for deciding the best stem cell source, administration route, and safety. This review strengthens the fact that why stem cell therapy is a promising candidate to treat DFU and cited multiple tissue engineering and biomaterial-based approaches for delivering stem cells and their aftermath paracrine events. Based on the pre-clinical and clinical studies, the review tried to come up with optimum stem cell source and delivery route for the treatment of DFU. At last, the review glances on possible direction to enhance therapeutics strategy for the same, including different approaches like: phytocompounds, exosomes, scaffold geometry, cell preconditioning and licensing etc.

Safety and stable survival of stem-cell-derived retinal organoid for 2 years in patients with retinitis pigmentosa.

Transplantation of induced pluripotent stem cell (iPSC)-derived retinal organoids into retinal disease animal models has yielded promising results, and several clinical trials on iPSC-derived retinal pigment epithelial cell transplantation have confirmed its safety. In this study, we performed allogeneic iPSC-derived retinal organoid sheet transplantation in two subjects with advanced retinitis pigmentosa (jRCTa050200027). The primary endpoint was the survival and safety of the transplanted retinal organoid sheets in the first year post-transplantation. The secondary endpoints were the safety of the transplantation procedure and visual function evaluation. The grafts survived in a stable condition for 2 years, and the retinal thickness increased at the transplant site without serious adverse events in both subjects. Changes in visual function were less progressive than those of the untreated eye during the follow-up. Allogeneic iPSC-derived retinal organoid sheet transplantation is a potential therapeutic approach, and the treatment's safety and efficacy for visual function should be investigated further.

Efectividad del tratamiento con plasma rico en plaquetas y leucocitos en la fisura anal secundaria / Effectiveness of Treating Secondary Anal Fissure with Platelet and Leukocyte-Rich Plasma

Introducción: El plasma rico en plaquetas es un producto derivado de la sangre, rico en péptidos y proteínas de señalización intercelular, así como citoquinas capaces de intervenir en cada una de las etapas de la regeneración de varios tejidos. Objetivo: Evaluar la efectividad del tratamiento con plasma rico en plaquetas y leucocitos en pacientes con fisura anal secundaria que asistieron a la consulta de Coloproctología del Hospital Docente Provincial Oncológico María Curie de Camagüey en el período de enero de 2020 a enero de 2023. Métodos: Se realizó un estudio cuasiexperimental. El universo lo conformaron todos los pacientes que acudieron a consulta en ese período. La muestra no probabilística intencionada la conformaron 130 pacientes adultos con diagnóstico de fisura anal secundaria que recibieron tratamiento con plasma rico en plaquetas y leucocitos. Resultados: El tiempo de cicatrización de la fisura anal permitió corroborar la efectividad del tratamiento; además, la mayoría de los pacientes evolucionaron de forma favorable. El dolor fue la complicación más visible pues presentó significación estadística al establecer la relación entre las variables. Se demostró que el tratamiento con plasma rico en plaqueta y leucocitos en pacientes con fisura anal secundaria es efectivo y seguro en la evaluación final del tratamiento. Conclusiones: Lo expuesto permite considerar que los pacientes tratados obtuvieron buenos resultados al hacer uso del plasma rico en plaquetas y leucocitos. Por consiguiente, tiene un resultado positivo en no mostrar complicaciones y una alta posibilidad de que el paciente tratado evolucione en mejor condición(AU)

Introduction: Platelet-rich plasma is a blood-derived product, rich in peptides and intercellular signaling proteins, as well as cytokines capable of intervening in each of the stages of regeneration of various tissues. Objective: To assess the effectiveness of treatment with platelet- and leucocyte-rich plasma in patients with secondary anal fissure who attended the coloproctology office at Hospital Docente Provincial Oncológico María Curie of Camagüey from January 2020 to January 2023. Methods: A quasiexperimental study was carried out, whose universe consisted of all the patients who came for consultation during that period. The nonprobabilistic purposive sample consisted of 130 adult patients with a diagnosis of secondary anal fissure who received treatment with platelet- and leucocyte-rich plasma. Results: The healing time of the anal fissure allowed corroborating the effectiveness of the treatment; in addition, most of the patients evolved favorably. Pain was the most visible complication since it presented statistical significance when the relationship between the variables were established. Treatment with platelet- and leucocyte-rich plasma in patients with secondary anal fissure proved effective and safe in the final assessment of the treatment. Conclusions: The above allows considering that the treated patients obtained good outcomes when making use of platelet- and leucocyte-rich plasma. Therefore, it has a positive outcome, not showing complications and a high possibility for the treated patient to evolve in a better condition(AU)

Regenerative Medicine Applied to Musculoskeletal Diseases in Equines: A Systematic Review.

Musculoskeletal injuries in horses have a great economic impact, predominantly affecting tendons, ligaments, and cartilage, which have limited natural regeneration. Cell therapy, which uses mesenchymal stem cells due to their tissue differentiation properties and anti-inflammatory and immunoregulatory effects, aims to restore damaged tissue. In this manuscript, we performed a systematic review using the Parsifal tool, searching the PubMed and Web of Science databases for articles on regenerative medicine for equine musculoskeletal injuries. Our review covers 17 experimental clinical studies categorized by the therapeutic approach used: platelet-rich plasma, conditioned autologous serum, mesenchymal stem cells, and secretome. These therapies reduce healing time, promote regeneration of fibrocartilaginous tissue, improve cellular organization, and improve joint functionality and sustainability. In conclusion, regenerative therapies using platelet-rich plasma, conditioned autologous serum, equine mesenchymal stem cells, and the emerging field of the secretome represent a promising and highly effective approach for the treatment of joint pathologies in horses, implying a valuable advance in equine healthcare.

Scalable production of homogeneous cardiac organoids derived from human pluripotent stem cells.

Three-dimensional (3D) cultures are known to more closely mimic in vivo conditions compared with 2D cultures. Cardiac spheroids (CSs) and organoids (COs) are useful for 3D tissue engineering and are advantageous for their simplicity and mass production for regenerative therapy and drug discovery. Herein, we describe a large-scale method for producing homogeneous human induced pluripotent stem cell (hiPSC)-derived CSs (hiPSC-CSs) and COs without scaffolds using a porous 3D microwell substratum with a suction system. Our method has many advantages, such as increased efficiency and improved functionality, homogeneity, and sphericity of hiPSC-CSs. Moreover, we have developed a substratum on a clinically relevant large scale for regenerative therapy and have succeeded in producing approximately 40,000 hiPSC-CSs with high sphericity at once. Furthermore, we efficiently produced a fused CO model consisting of hiPSC-derived atrial and ventricular cardiomyocytes localized on opposite sides of one organoid. This method will facilitate progress toward hiPSC-based clinical applications.