Regenerative Medicine Products Research Articles

Novel Insights into Pyrrolizidine Alkaloid Toxicity and Implications for Risk Assessment: Occurrence, Genotoxicity, Toxicokinetics, Risk Assessment-A Workshop Report.

This paper reports on the major contributions and results of the 2nd International Workshop of Pyrrolizidine Alkaloids held in September 2020 in Kaiserslautern, Germany. Pyrrolizidine alkaloids are among the most relevant plant toxins contaminating food, feed, and medicinal products of plant origin. Hundreds of PA congeners with widespread occurrence are known, and thousands of plants are assumed to contain PAs. Due to certain PAs' pronounced liver toxicity and carcinogenicity, their occurrence in food, feed, and phytomedicines has raised serious human health concerns. This is particularly true for herbal teas, certain food supplements, honey, and certain phytomedicinal drugs. Due to the limited availability of animal data, broader use of in vitro data appears warranted to improve the risk assessment of a large number of relevant, 1,2-unsaturated PAs. This is true, for example, for the derivation of both toxicokinetic and toxicodynamic data. These efforts aim to understand better the modes of action, uptake, metabolism, elimination, toxicity, and genotoxicity of PAs to enable a detailed dose-response analysis and ultimately quantify differing toxic potencies between relevant PAs. Accordingly, risk-limiting measures comprising production, marketing, and regulation of food, feed, and medicinal products are discussed.

Physiologic isolation and expansion of human mesenchymal stem/stromal cells for manufacturing of cell-based therapy products.

The utilization of mesenchymal stem/stromal cells raises new hopes in treatment of diseases and pathological conditions, while at the same time bringing immense challenges for researchers, manufacturers and physicians. It is essential to consider all steps along the in vitro fabrication of cell‐based products in order to reach efficient and reproducible treatment outcomes. Here, the optimal protocols for isolation, cultivation and differentiation of mesenchymal stem cells are required. In this review we discuss these aspects and their influence on the final cell‐based product quality. We demonstrate that physiological in vitro cell cultivation conditions play a crucial role in therapeutic functionalities of cultivated cells. We show that three‐dimensional cell culture, dynamic culture conditions and physiologically relevant in vitro oxygen concentrations during isolation and expansion make a decisive contribution towards the improvement of cell‐based products in regenerative medicine.

Deep Learning-Based In Vitro Detection Method for Cellular Impurities in Human Cell-Processed Therapeutic Products

Automated detection of impurities is in demand for evaluating the quality and safety of human cell-processed therapeutic products in regenerative medicine. Deep learning (DL) is a powerful method for classifying and recognizing images in cell biology, diagnostic medicine, and other fields because it automatically extracts the features from complex cell morphologies. In the present study, we construct prediction models that recognize cancer-cell contamination in continuous long-term (four-day) cell cultures. After dividing the whole dataset into Early- and Late-stage cell images, we found that Late-stage images improved the DL performance. The performance was further improved by optimizing the DL hyperparameters (batch size and learning rate). These findings are first report for the implement of DL-based systems in disease cell-type classification of human cell-processed therapeutic products (hCTPs), that are expected to enable the rapid, automatic classification of induced pluripotent stem cells and other cell treatments for life-threatening or chronic diseases.

Industrializing viral vector manufacture

Daniel Teasley has worked at Merck for over 6 years, serving in product management and product strategy roles across multiple portfolios including custom cell line engineering services, regenerative medicine products for research, cell therapy manufacturing, and viral gene therapy manufacturing. For the past three years, he has been a Senior Product Manager responsible for the development, launch, and marketing of products and services that enable at-scale viral vector manufacturing. He also supports cross-business strategic initiatives in novel modality manufacturing. Dr. Teasley holds a PhD in Molecular Genetics and Genomics from Washington University in St. Louis and a BS in Biology from the College of William and Mary.Katherine (Katie) Schewe has worked at Merck for over 4 years in various roles from product management in Viral & Gene Therapy to quality assurance of Active Pharmaceutical Ingredient manufacturing. Katie holds a MS in Chemistry from Indiana University Purdue University – Indianapolis and a BS in Chemistry from Southern Illinois University – Edwardsville.

Invitro effects of conditioned medium from bioreactor cultured human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on skin-derived cell lines.

IntroductionWhen stem cells are grafted into tissues, they differentiate and form specialized cells. However, the proficiency of stem cells to endure and assimilate the host cell is dependent on various growth factors and cytokines. According to various studies, these factors are available in the spent media of harvested stem cells, which can be used for treatment in regenerative medicine and cosmetic products. There are differences in cytokine secretion depending on the culture environment, which are clarified in this paper.MethodsHuman umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were cultured either in a bioreactor or in a flask. The conditioned medium from the hUC-MSC cultures in the flask and in the bioreactor was designated as “FM” and “BM”, respectively. We assessed the effects of FM and BM on UVB-induced oxidative stress, anti-aging, and melanogenic properties. The amount of growth factors, cell viability, hyaluronic acid (HA), pro-collagen, and pro-melanin were quantitatively evaluated in the FM and BM treated groups. The induction of HA and collagen synthesis was measured in CCD-986SK cells. For melanogenesis, the effects of FM and BM on melanin content and tyrosinase activity were measured in SK-MEL-31 cells.ResultsIn the present study, the secretion of growth factors, HA, and pro-collagen was significantly higher in the BM treatment, compared to that in the FM treatment. BM protected CCD-986SK cells against death from UVB induced oxidative stress. BM increased the promoter activity of the anti-oxidant genes SOD1, CAT, and GP; and downregulated the accelerating collagen decomposition gene, MMP-1, induced by UVB irradiation. In α-melanocyte-stimulating hormone (α-MSH) stimulated SK-MEL-31 cells, BM reduced melanin production and decreased the levels of MITF, tyrosinase, TRP-1, and TRP-2. These results suggest that BM could be used as a skin protection agent, because of its anti-apoptotic, anti-aging, and anti-melanogenic properties. This could be attributed to the differences in culturing methods; it is difficult to maintain the temperature and sterility in FM culture, when compared to that in the automated culturing conditions of the BM system.ConclusionsCollectively, our results indicate that using BM-conditioned hUC-MSC medium is very efficient process for producing raw materials for developing functional cosmetics.

Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine.

Cell therapy involves the transplantation of human cells to replace or repair the damaged tissues and modulate the mechanisms underlying disease initiation and progression in the body. Nowadays, many different types of cell-based therapy are developed and used to treat a variety of diseases. In the past decade, cell-free therapy has emerged as a novel approach in regenerative medicine after the discovery that the transplanted cells exerted their therapeutic effect mainly through the secretion of paracrine factors. More and more evidence showed that stem cell-derived secretome, i.e., growth factors, cytokines, and extracellular vesicles, can repair the injured tissues as effectively as the cells. This finding has spurred a new idea to employ secretome in regenerative medicine. Despite that, will cell-free therapy slowly replace cell therapy in the future? Or are these two modes of treatment still needed to address different diseases and conditions? This review provides an indepth discussion about the values of stem cells and secretome in regenerative medicine. In addition, the safety, efficacy, advantages, and disadvantages of using these two modes of treatment in regenerative medicine are also critically reviewed.

Regulatory and HTA early dialogues in medical devices

Introduction: Specific guidance and examples for health technology assessment (HTA) of medical devices are scarce in medical device development. A more intense dialogue of competent authorities, HTA agencies, and manufactures may improve evidence base on clinical and cost-effectiveness. Especially as the new Medical Device Regulation requires more clinical evidence.Methods: We explore the perceptions of manufacturers, competent authorities, and HTA agencies towards such dialogues and investigate how they should be designed to accelerate the translational process from development to patient access using semi-structured interviews. We synthesized the evidence from manufacturers, competent authorities, and HTA agencies from 14 different jurisdictions across Europe.Results: Eleven HTA agencies, four competent authorities, and eight manufacturers of high-risk devices expressed perceptions on the current situation and the expected development of three types of early dialogues.Discussion: The MDR has to be taken into account when designing the early dialogue processes. Transferring insights from medicinal product regulation is limited as the regulatory pathways differ substantially.Conclusion: Early dialogues promise to accelerate the translational process and to provide faster access to innovative medical devices. However, health policy-makers should promote and fully establish regulatory and HTA early dialogues before introducing parallel early dialogues of regulatory, HTA agencies, and manufacturers. For initiating change, the legislator must create the legal basis and set the appropriate incentives for manufacturers.

Legal principles of public administration for the invention of innovative medicines: European experience

Formulation of the problem. The creation of innovative medicines is the key to increasing the competitiveness of the pharmaceutical sector of Ukraine’s economy. Going through European integration requires bringing Ukrainian legislation, which regulates various sectors of the economy, in line with European legislation. The study of the European experience of legal regulation of medicines development is characterized by relevance. The state of the problem research. Problems of innovative activity in the field of medicines creation are investigated in scientific works of such Ukrainian scientists as V. M. Pashkov, S. V. Glibko, Yu. V. Heorgievsky, O. G. Alekseev, and T. A. Kolyada. European authors who have studied scientific activity problems in pharmacy are Philip A. Hines, Rosanne Janssens, Rosa Gonzalez-Quevedo, Ralf Arno Wess, and Constantinos Ziogas, Ivana Silvia. The purpose of the study is to develop proposals for amendments to Ukrainian legislation governing public administration in the sphere of medicines creation, taking into account the European experience. Presenting main material. State regulation of the creation of innovative medicines in Ukraine and the European Union is carried out in the following areas. The first is the creation and financial support of research institutions that develop innovative medicines. Second, the identification of research that needs public financial support on a competitive basis. Public administration bodies shall establish the procedure for registration of medicinal products or obtaining a trade license for placing a medicinal product on the market. Legislation and bylaws define the conditions for licensing the production of medicines. The differences in the legal regulation of the creation of medicines under Ukrainian and European legislation are as follows. First, in the European Union, licenses for marketing medicines are issued by the European Medicines Agency. At the same time, in Ukraine, the registration of medicines is entrusted to the Ministry of Health of Ukraine. Secondly, in the European Union, licenses for medicines production are issued by the national authorities of the EU member states. At the same time, the issuance of such licenses in Ukraine belongs to the competence of the State Service for Medicines Trafficking and Drug Control. Conclusions and prospects for further research. The implementation of European legislation governing the development of medicines may consist of further amendments to Ukrainian legislation in the field of circulation of medicines. Firstly, to consolidate the medicines registration function to the State Service for Medicines Trafficking and Drug Control of Ukraine. Secondly, to define one of the service’s tasks as providing advice to medicines developers on clinical and preclinical trials and medicines registration. It is also necessary to assess the environmental risk due to the use of a new medicinal product during its registration.

Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes

Date: July 22, 2020 If you were hurt or had a bad side effect following treatment with anything that was supposed to be a regenerative medicine product, including, for example, stem cell products and exosome products, we encourage you to report it to the FDA’s MedWatch Adverse Event Reporting

Executive Director’s Message

![Figure][1]</img> Dear ISHRS Members, The following information comes from my research while trying to understand the possible impact of the May 31, 2021, date that marked the end of the U.S. Food & Drug Administration’s (FDA’s) grace period for certain regenerative medicine products.

Safety of Medical Devices in Poland - Analysis of Withdrawn and Suspended Certificates of Compliance.

IntroductionIn the European Union, the process of controlling currently used medical devices is carried out and determined by legal provisions. The law stipulates that each entity responsible for using medical equipment must confirm its safety with an appropriate certificate issued by a notifying body. In Poland, the entity responsible for keeping records as to the withdrawn and suspended certificates, is the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products (URPL). Certification is required for all medical devices prior to their introduction onto the market and during their use.PurposeThe article presents data concerning the number of medical devices that failed to meet the certification criteria.MethodsThe research method is an analysis of available subject literature and a report on withdrawn and suspended certificates of medical devices in Poland.ResultsIn the years 2014–2020, the notified bodies withdrew and suspended 13,354 certificates for medical devices, of which 9792 certificates were withdrawn, 2852 suspended and one falsified.ConclusionThe suspension or withdrawal of a certificate for medical devices due to the inefficiency, obsolescence, imprecision, or safety of the devices is an action that improves the safety of patients. Such action reduces the number of medical damages and the obligation to pay compensation to those injured.

Ultraviolet-Visible Spectroscopy and Chemometric Strategy Enable the Classification and Detection of Expired Antimalarial Herbal Medicinal Product in Ghana.

To meet the growing demand for complementary and alternative treatment for malaria, manufacturers produce several antimalarial herbal medicinal products. Herbal medicinal products regulation is difficult due to their complex chemical nature, requiring cumbersome, expensive, and time-consuming methods of analysis. The aim of this study was to develop a simple spectroscopic method together with a chemometric model for the classification and the identification of expired liquid antimalarial herbal medicinal products. Principal component analysis model was successfully used to distinguish between different herbal medicinal products and identify expired products. Principal component analysis showed a clear class separation between all five herbal medicinal products (HMP) studied, with explained variance for first and second principal components as 37.51% and 26.38%, respectively, while the third principal component had 18.74%. Support vector machine classification gave specificity and accuracy of 1.00 (100%) for training set data for all the products. The validation set HMP1, HMP2, and HMP3 had sensitivity, specificity, and accuracy of 1.00. HMP4 and HMP5 had sensitivity and specificity of 0.90 and 1.00, respectively, and an accuracy of 0.98. The support vector machine classification and principal component analysis models were successfully used to identify expired herbal medicinal products. This strategy can be used for rapid field detection of expired liquid antimalarial herbal medicinal products.

Monitoring of residual solvent contamination in herbal medicinal products in Ghana: A pilot study

The use of herbal medicinal products for complementary and alternative medicine is well established in Ghana. The potential public health risks associated with the use of these products due to the presence of residual solvents have not yet been investigated and/or reported. In this pilot study, 7 liquid dosage forms of herbal medicinal products obtained from pharmacies and licensed chemical seller shops within the Accra metropolis in Ghana were investigated for the presence of 28 residual solvents using a combination of two orthogonal headspace gas chromatography with flame ionization detector methods from a compendial approach in the general chapter <467> Residual Solvents in the United States Pharmacopeia without modification. One herbal medicinal product was contaminated with 498.33 ppm of chloroform, resulting in daily exposure of 41.82 mg/day, which is above the permissible daily exposure level of 0.6 mg/day. The detection of chloroform in herbal medicinal products suggests further investigation into the profile of residual solvent contaminants in herbal medicinal products as a matter of public health concern and the potential need for more stringent regulation of herbal medicinal products marketed in Ghana.

Bioprocess and analytics priorities for the tissue engineered product and cell therapy fields

Julie Allickson, PhD is Chief Manufacturing Development Center Officer at Wake Forest Institute for Regenerative Medicine. She heads the clinical translation team streamlining development to create a robust pipeline of products in development and early phase clinical trials including cellular therapy, genetically engineered cellular therapy, tissue engineered organs and tissues, biomaterials and devices. Prior to the Institute, she was the Vice President of Research and Development and Laboratory Operations for Cryo-Cell International Inc. Dr. Allickson has 30 years of experience in clinical translation of cellular therapies and regenerative medicine products including regulatory affairs, business management and board directorship experience. Other experience as an executive officer of a publicly traded company building services for cellular banking including licensure of technology. Dr. Allickson was part of the team to perform the first Bone Marrow Transplant at the University of Miami in 1990’s and at Miami Children’s Hospital Bone Marrow Transplant Program. She has a Doctorate in Health Sciences- Clinical Immunology along with a Master’s Degree in Medical Laboratory Sciences. She is one of the founding members of the International Society of Cellular Therapy. She is on the Board of Directors for AABB Board, Regenerative Medicine Outcomes Foundation as a scientific advisor and Scientific Advisory Board for Alliance for Cell Therapy Now. She is an Associate Editor for Journal of Translational Medicine, on the Editorial board of CELLR4, Vice Chair for Cord Blood Association Quality Committee, Technical Advisory Board for Tissue Engineered Products under ICCBBA, grant reviewer for state funded initiatives such as CIRM and serves on the ISCT Commercialization Committee.

Proven and unproven cell therapies – what we have learned so far?

The exciting advancement in cell therapies in both cancer and regenerative medicine provides alternative therapeutic opportunities for patients with advanced diseases who have exhausted all treatment options. However, with the emergence of new technologies and innovations this also brings about “unproven” cell‐ and tissue‐based interventions that have not been fully evaluated in clinical trials. Such interventions have resulted in injuries and deaths in patients. Collectively, these practices increase the potential for patient exploitation and harm through the imposition of medical and financial risks. Recognizing this worrying situation, in April 2020, European Medicine Agency (EMA), committee for Advances Therapies advised patients and the general public to be cautious unproven cell‐based therapies. Likewise, the Food and Drug Administration (FDA) has posted information about products marketed as stem cells, mesenchymal stromal cells (MSCs) or other regenerative medicine products, including the conditions for which they are approved, and which products are not approved. Though both EMA and FDA recognize the promise of cell‐based therapies for treating patients with serious diseases, both concur that well‐designed clinical trials and regulatory oversight are necessary to ensure safety, efficacy and quality of the therapies. In this review, I will mention proven cell therapies in the haematopoietic stem cell transplant setting and in the form of chimeric antigen receptor (CAR) T‐cell therapies and briefly mention how these therapies have evolved over time, the learning curve and scientific progress in these therapies. I will then mention briefly about MSCs and focus on both the proven and unproven aspects of MSC.

STUDY OF TOLERANCE OF THE DRUG BASED ON QUARTZETIN BY BLOOD INDICATORS IN CLINICALLY HEALTHY DOGS

The article presents the results of clinical trials of tolerance of the drug, containing the flavonoid quercetin, on clinically healthy dogs. Quercetin is a biologically active substance that can have antioxidant, membrane, gastro-, nephro-, hepato-, cardioprotective, antiplatelet, anti-inflammatory effects. The flavonoid quercetin belongs to the aglycones of many plant flavonoid glycosides of higher plants. Some pharmacological effects of quercetin have been discovered recently, but the prospects of its use in veterinary medicine are being intensively studied, given its promising positive effects on the animals` body. The bioavailability of quercetin is highest in combination with pectin and insoluble oligosaccharides, which is associated with changes in the quantitative and qualitative composition of the mammals’ intestinal micro flora. A prerequisite for the development and testing of new veterinary medicinal products in accordance with the requirements of the international community for the registration of medicinal products is the conduct of clinical trials in compliance with the requirements of "Good Clinical Practice" (GCP). The introduction of biologically active drugs in the practice of veterinary medicine requires careful researches on target species of animals. Therefore, to assess the tolerability, safety and efficiency of the drug containing quercetin, a comprehensive clinical trial was performed on small pets (dogs). The study was conducted in veterinary clinics on healthy dogs of all ages, genders and breeds. The drug was used at a dose of 4 mg/kg body weight orally with food for 30 days. Blood sampling in test animals was performed before drug use and on days 30 and 60 of the experiment. The effect of the drug on the body was evaluated by clinical indicators, hematological and biochemical parameters of dogs' blood. Stabilized EDTA blood was used for morphological studies and blood serum for biochemical studies.&#x0D; According to the evaluation of the animals’ clinical condition and the obtained data of laboratory studies, it was found that the tolerance of the studied drug, administered orally to healthy dogs, was good. According to the results of comparison of clinical, hematological and biochemical parameters on the 30th and 60th day of the study with the initial data obtained before the use of the study drug, no negative changes were detected.&#x0D; Hematological studies indicated the activation of hematopoietic processes, normalization of leukogram parameters on 30th day after the drug application. Changes in the lymphocytes` content in the leukogram and the γ-globulin fraction in the protein-gram indicated a strengthening of dogs` immune protection.&#x0D; The results of biochemical studies of dogs's blood on the 30th day showed a reliable increase, within normal limits, in glucose, creatinine contents, increased catalase and alanine aminotransferase activity and decreased gamma-glutamyltransferase activity and the contents of diene conjugates and malonic dialdehyde.&#x0D; Activation of protein metabolism was established, which was indicated by a reliable increase in the total serum protein content and albumin content in the dogs` proteinogram. On the 60th day of the drug application no significant changes in hematological and biochemical parameters of the blood of dogs were detected. There was a slight decrease in the activity of catalase and SOD and a decrease in the content of malonic dialdehyde in the serum of dogs, compared with the values on the 30th day. This, in turn, showed a decrease in the intensity of the formation of toxic compounds in animals and pronounced antioxidant properties of the drug Hepanephran.

Standards efforts and landscape for rapid microbial testing methodologies in regenerative medicine

The Standards Coordinating Body for Gene, Cell, and Regenerative Medicines and Cell-Based Drug Discovery (SCB) supports the development and commercialization of regenerative medicine products by identifying and addressing industry-wide challenges through standards. Through extensive stakeholder engagement, the implementation of rapid microbial testing methods (RMTMs) was identified as a high-priority need that must be addressed to facilitate more timely release of products. Since 2017, SCB has coordinated efforts to develop standards for this area through surveys, weekly meetings, workshops, leadership in working groups and participation in standards development organizations. This article describes the results of these efforts and discusses the current landscape of RMTMs for regenerative medicine products.Based on discussions with stakeholders across the field, an overview of traditional culture-based methods and limitations, alternative microbial testing technologies and current challenges, fit-for-purpose rapid microbial testing and case studies, risk-based strategies for selection of novel rapid microbial test methods and ongoing standards efforts for rapid microbial testing are captured here. To this end, SCB is facilitating several initiatives to address challenges associated with rapid microbial testing for regenerative medicine products. Two documentary standards are under development: an International Organization for Standardization standard to provide the framework for a risk-based approach to selecting fit-for-purpose assays primarily intended for cell and gene therapy products and an ASTM standard guide focused on sampling methods for microbial testing methods in tissue-engineered medical products. Working with the National Institute of Standards and Technology, SCB expects to facilitate the process of developing publicly available microbial materials for inter-laboratory testing. These studies will help collect the data necessary to facilitate validation of novel rapid methods. Finally, SCB has been working to increase awareness of, dialog about and participation in efforts to develop standards in the regenerative medicine field.

Efficient and robust induction of retinal pigment epithelium cells by tankyrase inhibition regardless of the differentiation propensity of human induced pluripotent stem cells

Transplantation of retinal pigment epithelium (RPE) cells derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs) hold great promise as a new therapeutic modality for age-related macular degeneration and Stargardt disease. The development of hESC/hiPSC-derived RPE cells as cell-based therapeutic products requires a robust, scalable production for every hiPSC line congruent for patients. However, individual hESC/hiPSC lines show bias in differentiation. Here we report an efficient, robust method that induces RPE cells regardless of the differentiation propensity of the hiPSC lines. Application of the tankyrase inhibitor IWR-1-endo, which potentially inhibits Wnt signaling, promoted retinal differentiation in dissociated hiPSCs under feeder-free, two-dimensional culture conditions. The other tankyrase inhibitor, XAV939, also promoted retinal differentiation. However, Wnt signaling inhibitors, IWP-2 and iCRT3, that target porcupine and β-catenin/TCF, respectively, did not. Further treatment with the GSK3β inhibitor CHIR99021 and FGF receptor inhibitor SU5402 induced hexagonal pigmented cells with phagocytotic ability. Notably, the IWR-1-endo-based differentiation method induced RPE cells even in an hiPSC line that expresses a lower level of the differentiation propensity marker SALL3, which is indicative of resistance to ectoderm differentiation. The present study demonstrated that tankyrase inhibitors cause efficient and robust RPE differentiation, irrespective of the SALL3 expression levels in hiPSC lines. This differentiation method will resolve line-to-line variations of hiPSCs in RPE production and facilitate clinical application and industrialization of RPE cell products for regenerative medicine.

Bioinspired in vitro microenvironments to control cell fate: focus on macromolecular crowding.

The development of therapeutic regenerative medicine and accurate drug discovery cell-based products requires effective, with respect to obtaining sufficient numbers of viable, proliferative, and functional cell populations, cell expansion ex vivo. Unfortunately, traditional cell culture systems fail to recapitulate the multifaceted tissue milieu in vitro, resulting in cell phenotypic drift, loss of functionality, senescence, and apoptosis. Substrate-, environment-, and media-induced approaches are under intense investigation as a means to maintain cell phenotype and function while in culture. In this context, herein, the potential of macromolecular crowding, a biophysical phenomenon with considerable biological consequences, is discussed.

Use of platelet concentrate gel in second-intention wound healing: a case\xa0report

BackgroundWound healing is a complex and dynamic process. Healing of acute and chronic wounds can be impaired by patient factors (that is, comorbidities) and/or wound factors (that is, infection). Regenerative medicine products, such as autologous/homologous platelet-rich plasma gel, may speed up the healing process. Autologous/homologous platelet-rich plasma is an advanced wound therapy used for hard-to-heal acute and chronic wounds. The cytokines and growth factors contained in platelet-rich plasma play a crucial role in the healing process.Case presentationA 61-year-old Caucasian male patient, suffering from mental retardation following meningitis, with a transplanted kidney due to prior renal impairment, and under immunosuppressant therapy, was submitted to aneurysmectomy of his proximal left forearm arteriovenous fistula. A few days later, the patient came to our attention with substantial blood loss from the surgical site. The wound presented no signs of healing, and after fistula reparation and considering persistent infection of the surgical site (by methicillin-resistant Staphylococcus aureus), surgeons decided for second-intention healing. To favor healing, 10 mL homologous platelet concentrate gel was sequentially applied. After each application, wound was covered with nonadherent antiseptic dressing. After only seven applications of homologous platelet concentrate gel, wound completely recovered and no amputation was necessary.ConclusionsTopical application of homologous platelet-rich plasma gel in healing wound shows beneficial results in wound size reduction and induces granulation tissue formation. Platelet-rich plasma could be a safe and cost-effective treatment for managing the cutaneous wound healing process to shorten the recovery period and thereby improve patient quality of life.