Regenerative Medicine Products Research Articles

Pilot Study: Use of Stem Cell Therapy and Diced Cartilage in Secondary Rhinoplasty Cases Clinical Outcomes: The Golden Turkish Delight.

Although many techniques in the secondary rhinoplasty field have been developed in recent years, there are debates regarding achieving results with a high satisfaction rate. We aimed to share the surgical use technique in secondary rhinoplasty patients by enriching the Turkish delight technique with mesenchymal stem cells, which we described as the golden Turkish delight (GTD) technique, and the long-term patient satisfaction results. The study was planned as prospective research, and 30 secondary rhinoplasty patients who presented to our service for rhinoplasty were included. The GTD technique was applied to these patients. The patient's satisfaction with the surgical procedure was evaluated at least 9-12 months after the surgery, and the Global Aesthetic Improvement Scale (GAIS) was used as a measurement tool. Of the participants, the satisfaction levels of 30 patients were evaluated with a 1-year follow-up on average, and the rate of those who improved was found to be 80% using the GAIS score. The rate of those with high GAIS scores and those with high satisfaction levels was approximately 56%. Twenty percent of the patients were not satisfied with the result. When we evaluate the postoperative 1-year results of our patients in terms of satisfaction and complications, we may state that the absorption that may occur in the Turkish delight technique over time could give better results with the GTD technique. In addition to GTD and fat graft support, regenerative medicine products such as stromal vascular fraction are very effective in obtaining favorable results.

A Review on a Drug Registration Process in United Kingdom

This review outlines the regulatory modifications in several pharmaceutical industries that have been impacted by Brexit and develops new standards-based recommendations from the Medicines and Healthcare Products Regulatory Agency (MHRA). To get insight into the regulatory changes that occurred in the pharmaceutical industry during the dissolution of Europe and Britain, retrospective and contemporaneous reviews were used. As the transition period concluded, the MHRA issued a library of new guidelines on January 1, 2021. The several pharmaceutical industries covered by this guidance include clinical trials, medical equipment, imports and exports of Pharmaceuticals and Cosmetics. The Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for approving medicinal products in the UK. The agency offers various routes for marketing authorisation, including national, international, and decentralised procedures. The national routes include a 150-day assessment, rolling review, European Commission (EC) Decision Reliance Procedure, decentralised and mutual recognition reliance procedure, and unfettered access procedure for marketing authorisations approved in Northern Ireland. International routes include Project Orbis and Access Consortium. Applicants must submit their applications through the MHRA submissions portal in electronic Common Technical Document (eCTD) format. The agency verifies the technical validity of submissions using the Lorenz Docubridge validation tool. The MHRA offers fast-track marketing authorisation for products with strong public health benefits or those addressing supply shortages. Applications that do not meet guidelines will be rejected, and applicants must resubmit after correcting errors. Understanding MHRA guidelines and requirements facilitates market entry for medicinal products in the UK. Conclusion: Any medicinal agent to be marked in the United Kingdom has to follow the guidelines and regulations given by the MHRA a regulatory authority which approve drug products. The objective of the review article is to highlights information regarding the requirements. Different types routes in registration of medicinal products in a market in the United Kingdom knowing the requirements of the MHRA guidelines, it is too easy for a product to get into the UK market.

Immunophenotyping of a population of cultured human umbilical cord cells from Wharton's jelly

BACKGROUND: Against the background of many existing methods of defect replacement in post-traumatic injuries the methods of repair of damaged tissues based on methods using products of tissue engineering and cultures of artificially cultured human cells are becoming more and more widespread in medical practice. The literature reports weak immunogenic activity of human umbilical cord tissues, which makes these cells promising components of regenerative medicine products. Due to possible errors in explant selection and cell transformation in the process of cultivation, it is necessary to reliably determine the phenotype of cells obtained as a result of tissue explantation and their further cultivation. Thus, the specificity of obtaining multipotent mesenchymal cells from human umbilical cord Warton's stool tissues requires reliable identification of the type of the obtained cells. AIM: To obtain reliable features of mesenchymal stem cells in the cell population obtained from human umbilical cord stool tissue. MATERIAL AND METHODS: Methods of cell cultivation, flow cytofluorimetry, immunocytochemistry for determination of surface and intracellular markers of mesenchymal stem cells were used in the study. RESULTS: In the course of work on the identification of cells of the population obtained by culturing explants from human umbilical cord Wharton stool, the heterogeneity of the type of cells constituting the cell population was established. Most of them are mesenchymal stem cells carrying fluorescent markers CD45, CD73, CD34, CD29, CD90, CD44, CD105, which agrees with the immunophenotype of mesenchymal stem cells defined by the International Society for Cell Therapy. The ratio of the applied markers allows us to refer the population of cells obtained by direct explantation of Varton's gelatin tissue fragments to mesenchymal stem cells. Visual control confirmed the localisation of labelled antibodies on the surface of cultured cells. And also, it was shown that there were no vascular muscle cells in the obtained culture. CONCLUSION: As a result of experiments on identification of the cells obtained during explantation of Wharton's jelly tissue fragments and their further cultivation, their belonging to mesenchymal stem cells was established by immunofluorescence cytophotometry.

Use of regenerative medicine in the treatment of endometritis in mares: A systematic review and meta-analysis

Defining the optimal therapy for endometritis remains a significant challenge for clinicians. Given the public health threat posed by antibiotic resistance and the inconclusiveness of traditional therapies, regenerative medicine has been proposed as an alternative. The objective of this study was to conduct a comprehensive systematic review and meta-analysis, to investigate the efficacy of regenerative medicine products in the treatment of both post-breeding persistent and chronic degenerative endometritis (PBIE/CDE) in mares, following the PRISMA guidelines. This research could be a comprehensive scientific reference for determining appropriate treatments and clinical strategies.All studies exploring the use of regenerative medicine therapies (i.e., plasma products, autologous conditioned serum, mesenchymal stem cells MSCs, and MSC derivatives) in the treatment of PBIE/CDE were included, regardless of the specific protocol used, the evaluated outcomes, or the diagnostic method employed. Two authors independently gathered data and evaluated the risk of bias for each study. Treatment effects were assessed using risk ratios for dichotomous data, accompanied by 95 % confidence intervals. Data were aggregated utilizing the fixed-effects model. The quality of evidence for each outcome was evaluated using GRADE criteria.Eighteen studies were included in the systematic review, while fifteen trials were included in the meta-analysis. A sub-meta-analysis was conducted separately on platelet-derived products, as well as on MSCs and their derivatives. The results demonstrated an overall positive effect of regenerative therapies in treating PBIE/CDE, particularly those involving MSCs and their derivatives. The positive outcomes include an anti-inflammatory effect, characterized by reduced intrauterine fluid accumulation, neutrophils, and cytokine concentrations. Additionally, improvements in pregnancy, foaling, and embryo recovery rates have been observed in some cases. Despite the limited number of randomized controlled studies and the high variability among protocols, including the timing of treatment, type, and volume of products used, the use of regenerative products, especially MSCs and their derivatives, has promising results in terms of both efficacy and safety for treating PBIE/CDE in mares.

Stem Cells and Stem Cell-Derived Factors for the Treatment of Inflammatory Bowel Disease with a Particular Focus on Perianal Fistulizing Disease: A Minireview on Future Perspectives.

Inflammatory bowel disease remains a difficult disease to effectively treat, especially fistulizing Crohn's disease. Perianal fistulas in the setting of Crohn's disease remain an area of unmet need with significant morbidity in this patient population. Up to one third of Crohn's patients will have perianal fistulizing disease and current medical and surgical interventions are of limited efficacy. Thus, most patients experience significant morbidity, narcotic use, and loss of employment and end up with multiple surgical interventions. Mesenchymal stem cells (MSCs) have shown efficacy in phase 3 clinical trials, but considerable infrastructure challenges make MSCs limited with regard to scalability in clinical practice. Extracellular vesicles, being derived from MSCs and capturing the secretome functionality of MSCs, offer similar physiological utility regarding mechanism, while also providing an off the shelf regenerative medicine product that could be widely used in daily clinical practice.

J-TEC's efforts to industrialize regenerative medicine in Japan

Japan Tissue Engineering Co., Ltd., J-TEC, was launched in 1999 to industrialize regenerative medicine in Japan. We developed the first regenerative medicine product, JACE (autologous cultured epidermis), which received PMDA approval for treating serious burns in 2007. Then, JACC (autologous cultured cartilage), the second product, was approved in 2012 for efficacy on traumatic cartilage defects. In 2014, the Pharmaceutical Affairs Law was revised to the Pharmaceutical and Medical Device Act, and regenerative medicine products, including gene therapies, were newly classified to accelerate productization. Subsequently, Nepic (autologous cultured corneal epithelium) and Ocural (autologous cultured oral mucosal epithelium) for epithelialization of limbal stem cell deficiencies in ophthalmology were approved in 2020 and 2021, respectively. Furthermore, a new product, JACEMIN (autologous cultured epidermis maintaining melanocyte) for vitiligo treatment was approved in 2023. We have developed five products of regenerative medicine that construct human tissues to graft rather than injectable cell suspensions like drugs. To develop regenerative medicine products, it is necessary to ensure the safety of raw materials, standardize the cultivation process, examine cell characteristics on GLP tests, construct transportation methods, build GCTP facilities, and conduct clinical trials on GCP. Re-examinations of JACE for serious burns and JACC for cartilage defects were completed after 7 years of all-case postmarketing surveillance. The commercialization of these products has become a benchmark for domestic regulation and has induced the development of a regenerative medicine industry promoted by Japan.

Identification of unapproved orthopedic regenerative medicine: Usefulness of the Act on Safety of Regenerative Medicine

In Japan, the Act on Safety of Regenerative Medicine regulates unapproved regenerative medicine. Other nations market regenerative medicine products, bypassing regulatory approval. To identify unapproved orthopedic regenerative medicine, we have used data based on the Act. Platelet-rich plasma was often used. The common target was the knee. Prices averaged $2,490.

In vitro maturation of mouse oocytes in dose-dependent manner of platelet concentrate-derived lysates

Platelet concentrates (PCs) including platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are extensively used as autologous products in regenerative medicine. In this study, the effects of different concentrations of platelet concentrate-derived lysates (PC-Ls) including PRP-derived lysate (PRP-L) and PRF-derived lysate (PRF-L) were demonstrated separately on the oocyte maturation. Since then, the effectiveness and appropriate concentration of PC-Ls will be confirmed which will be the premise for studies on improving the composition of oocyte maturation medium utilizing active components of autologous origin. The complexes of oocyte-cumulus-granulosa (COCGs) were collected from mature female mice (6-8 weeks old, Mus musculus var. Albino). The maturation medium (M-199 medium) for the COCGs was supplemented with 5%, 10%, 15% PRP-L and 5%, 10% and 15% PRF-L. Oocytes were assessed for maturity after 24 hours and 48 hours of culture through morphological (polar body appearance and developmental stage of oocyte, follicular cell morphology) and functional (in vitro fertility) evaluation. First, all groups showed the same oocyte morphology which included the first polar body. However, the development of follicular cells only happened in the groups treated with 10%, 15% PRP-L and 10%, 15% PRF-L during the culture phase. The 15% PRF-L group had the most significant proportion of mature oocytes after 24 hours of culture which was 22.88%. After 48 hours of culture, this number rose to 50.67% in the 10% PRF-L treatment group (P-value 0.05). The percentage of developed oocytes from the 10% PRF-L treatment that could be fertilized was 41.67%. The platelet concentrates-derived lysates promoted oocyte maturation independently and PRF-L supported oocyte development better than PRP-L. This study suggested a novel role for second-generation platelet concentrates (PRF) in in vitro oocyte maturation. The culture time should not be extended to 48 hours.

Beneficial Effects of Castanea sativa Wood Extract on the Human Body and Possible Food and Pharmaceutical Applications.

The aim of this review was to investigate the potential use of Castanea sativa wood extract as a food supplement and to evaluate its beneficial properties for human health. The results of the limited amount of studies suggest promising properties, including potential anti-inflammatory effects. The literature indicates that the extract, which is rich in bioactive compounds such as tannins, offers promising therapeutic possibilities for the treatment of conditions associated with chronic inflammation. Consequently, interest in its use in food and pharmaceuticals is growing. Phytochemical studies have reported antioxidant and antimicrobial activities, and anti-inflammatory, anticancer, hypolipidemic, hypoglycemic, and neuroprotective activities. A suitable extraction method and solvent is crucial for the isolation of bioactive compounds, being green extraction technologies outstanding for the industrial recovery of chestnut wood's bioactive compounds. Nevertheless, it is important to emphasize the importance of adhering to regulatory guidelines and obtaining the necessary approvals from regulatory authorities to ensure product safety and compliance. The regulation of herbal medicinal products with proven efficacy and traditional herbal medicinal products is well defined, monitored by authorized bodies, and subject to strict control measures. It is noteworthy that medicinal products are subject to stringent quality testing to ensure safety and efficacy in use, whereas there are no comparable regulatory standards and specific labeling requirements for dietary supplements. When using herbal products, compliance with established standards in health research is essential.

Size Control of Biomimetic Curved-Edge Vaterite with Chiral Toroid Morphology via Sonochemical Synthesis.

The metastable vaterite polymorph of calcium carbonate (CaCO3) holds significant practical importance, particularly in regenerative medicine, drug delivery, and various personal care products. Controlling the size and morphology of vaterite particles is crucial for biomedical applications. This study explored the synergistic effect of ultrasonic (US) irradiation and acidic amino acids on CaCO3 synthesis, specifically the size, dispersity, and crystallographic phase of curved-edge vaterite with chiral toroids (chiral-curved vaterite). We employed 40 kHz US irradiation and introduced L- or D-aspartic acid as an additive for the formation of spheroidal chiral-curved vaterite in an aqueous solution of CaCl2 and Na2CO3 at 20 ± 1 °C. Chiral-curved vaterites precipitated through mechanical stirring (without US irradiation) exhibited a particle size of approximately 15 μm, whereas those formed under US irradiation were approximately 6 μm in size and retained their chiral topoid morphology. When a fluorescent dye was used for the analysis of loading efficiency, the size-reduced vaterites with chiral morphology, produced through US irradiation, exhibited a larger loading efficiency than the vaterites produced without US irradiation. These results hold significant value for the preparation of biomimetic chiral-curved CaCO3, specifically size-reduced vaterites, as versatile biomaterials for material filling, drug delivery, and bone regeneration.

Selective elimination of tumorigenic cells from mixed culture of normal and tumorigenic cells using hybrid liposomes aimed at realizing of cell therapy

While induced pluripotent stem (iPS) cells are expected to be a cell source for regenerative medicine, they also have tumorigenic properties owing to their proliferative potential. During the manufacturing of regenerative medicine products, undifferentiated iPS cells and malignant transformed cells may be mixed in the cell culture population. Therefore, it is essential to eliminate tumorigenic cells selectively. In this study, a mixed culture of normal human fetal hepatocytes (Hc cells) and human hepatocellular carcinoma cells (HuH-7 cells) was used as a cell population model to be used as regenerative medicine products, and the selective elimination of HuH-7 cells by hybrid liposomes (HL) was analyzed. HL tended to fuse and accumulate more in HuH-7 cells due to larger fluidity of plasma membrane for HuH-7 cells than that for Hc cells. In a mixed culture of Hc and HuH-7 cells, HL selectively eliminated HuH-7 cells while allowing Hc cells to remain viable. In addition, HL treatment for the mixed culture of Hc and HuH-7 cells suppressed the tumorigenicity of HuH-7 cells. Therefore, HL selectively fused and accumulated in tumorigenic cells in a mixed cell culture of normal and tumorigenic cells, and eliminated tumorigenic cells while allowing normal cells to remain viable. The results of this study suggest the potential of HL in eliminating tumorigenic cells during the manufacturing of regenerative medicine products. Thus, HL could be expected to contribute to the development of safe regenerative medical products.

Specifics of Cryopreservation of Hydrogel Biopolymer Scaffolds with Encapsulated Mesenchymal Stem Cells.

The demand for regenerative medicine products is growing rapidly in clinical practice. Unfortunately, their use has certain limitations. One of these, which significantly constrains the widespread distribution and commercialization of such materials, is their short life span. For products containing suspensions of cells, this issue can be solved by using cryopreservation. However, this approach is rarely used for multicomponent tissue-engineered products due to the complexity of selecting appropriate cryopreservation protocols and the lack of established criteria for assessing the quality of such products once defrosted. Our research is aimed at developing a cryopreservation protocol for an original hydrogel scaffold with encapsulated MSCs and developing a set of criteria for assessing the quality of their functional activity in vitro. The scaffolds were frozen using two alternative types of cryocontainers and stored at either -40 °C or -80 °C. After cryopreservation, the external state of the scaffolds was evaluated in addition to recording the cell viability, visible changes during subsequent cultivation, and any alterations in proliferative and secretory activity. These observations were compared to those of scaffolds cultivated without cryopreservation. It was shown that cryopreservation at -80 °C in an appropriate type of cryocontainer was optimal for the hydrogels/adipose-derived stem cells (ASCs) tested if it provided a smooth temperature decrease during freezing over a period of at least three hours until the target values of the cryopreservation temperature regimen were reached. It was shown that evaluating a set of indicators, including the viability, the morphology, and the proliferative and secretory activity of the cells, enables the characterization of the quality of a tissue-engineered construct after its withdrawal from cryopreservation, as well as indicating the effectiveness of the cryopreservation protocol.

Программы раннего доступа лекарственных препаратов: опыт БРИКС, Европейского Союза, Соединенных Штатов Америки

Timely accessibility of effective and safe medicinal products is one of the main tasks of healthcare. The goal of the present review is to assess various approaches that provide an early access to medicinal products within the BRICS group (list of participants as of 01.10.2023), European Union and United States of America. The stage of the life cycle of medicinal products is closely associated with their further movement in the market, patient access rate, and partially with the issues of their financing and reimbursement, which directly influence their affordability for population. The article contains data about the specifics of expanded access to unregistered medicinal products used on a compassionate basis and presenting therapy under early access programs financed by pharmaceutical companies; it also describes approaches to accelerated registration and registration of medicinal products in case of limited clinical data. Experience of the reviewed countries in early access programs is described.

ПРАВИЛА РЕГИСТРАЦИИ И ЭКСПЕРТИЗЫ ЛЕКАРСТВЕННЫХ СРЕДСТВ В РАМКАХ ЕВРАЗИЙСКОГО ЭКОНОМИЧЕСКОГО СОЮЗА: ОЦЕНКА КЛЮЧЕВЫХ ИЗМЕНЕНИЙ

The formation of a common pharmaceutical market within the framework of the Eurasian Economic Union requires the harmonization and unification of procedures for registration and examination of medicines. Changes made annually to the Rules for Registration and Expertise, their analysis and evaluation contribute to the optimization of this process. The goal is to evaluate the key changes made to the Rules for Registration and Expertise of Medicines over the past two years by a group of experts. Materials and methods. The expert group included 38 specialists with experience in registration of medicinal products and making changes to the registration dossier. The evaluation was carried out according to the Likert scale using the developed expert evaluation card. Results. It is shown that, in general, experts are very positive about the changes, both from the standpoint of their practical significance and the optimal ratio of stability and flexibility, and in terms of accuracy, correctness and clarity of formulations. Particularly noted were the creation of the necessary conditions for the active circulation of orphan drugs, their accelerated use in a number of individual cases, the increase in the availability of unregistered drugs in special cases, the exclusion of the annual re-evaluation of the “benefit-risk” indicator for a number of drugs, accelerating mutual recognition procedures in several Member States through simultaneous initiation. Conclusion. The strengths and weaknesses of the amendments to the Rules for Registration and Expertise of Medicines have been established. The need for a more detailed consideration of the amendments concerning the terms of the procedures for registration and expertise of medicines, as well as the assessment of changes in the annexes to the Rules, is shown.

Attitudes Towards Standardization of Mesenchymal Stromal Cells-A Qualitative Exploration of Expert Views.

Pharmacopoeial standards ensure quality control of established medicines. It is widely believed that translation of cell therapy medicines will be facilitated by defining and adopting relevant standards. Mesenchymal stromal cells (MSCs) are used extensively for multiple indications in regenerative medicine. They are highly heterogeneous in terms of their biological characteristics and their mechanisms of action, making standardization a challenging undertaking. Furthermore, the use of MSCs in therapy appears to attract diverse views, ranging from concern and caution to enthusiastic positivity. We conducted semi-structured interviews with 20 expert stakeholders from academia, industry, regulatory agencies, non-governmental organizations and clinicians to explore their views, experiences, recommendations, and concerns regarding standardization of MSCs. Qualitative thematic analysis of transcribed records led to development of a consensus framework, which identified 5 key themes to facilitate exploration of the interviews' content. On the basis of our findings, we conclude that (1) there is undoubtedly an appetite for standardization, particularly in development of assays that enable comparison or benchmarking across manufacturers, processes, and cell sources; (2) stakeholder groups are not homogeneous in their concerns and attitudes; (3) careful consideration must be given to the points along the development timeline at which different standardization approaches could be beneficial; and (4) the roles of standards could be promoted further for specific aspects of advanced therapy medicinal product (ATMP) development and regulation such as qualification of decentralized manufacturing sites. A unified cross-stakeholder approach will help to advance MSC therapeutics and other cell therapy medicines.

Development of 3D cellular products based on unique AM technology, and its contribution to medical care

Cyfuse Biomedical K.K. is a R&D venture company established in 2010 aiming at industrialization of its 3D cellular products for regenerative medicine based on innovative 3D cell stacking technology, and has newly listed on the Growth Market of the Tokyo Stock Exchange in December 2022. We are developing 3D cellular products consisted of only human cells through our unique platform technology created from the fusion of two disparate technologies; engineering and biology. Three pipelines aiming for approval as products for regenerative medicine have already advanced to the stage of human clinical trials, and are expected to implemented in society in the near future. In addition, we also have been developing functional cellular devices (FCD) using our core technology, the Kenzan method, and have begun marketing FCD as support tools that contribute to the development of new drugs. We will introduce in detail our contribution to the medical field that we are aiming for, with specific examples, also referring to the unique additive manufacturing (AM) technology that supports the realization of our cellular products as above.

Advances in corneal regenerative medicine with iPS cells.

The cornea is a pioneering area of regenerative medicine, and Japanese researchers have led the world in this field. In Japan, 3 different epithelial sheet regenerative medicine products have been approved for corneal epithelial stem cell deficiency, and the first-in-human studies of cultured corneal endothelial cell suspension transplants, induced pluripotent stem cell (iPS cell)-derived corneal epithelial sheet transplants, and iPS cell-derived corneal endothelial substitute cell transplants were all conducted and reported globally for the first time by Japanese researchers. In the field of corneal epithelial regenerative medicine, Pellegrini et al. (Lancet 349:990-3, 1997) performed the first in-human transplant of autologous cultured corneal epithelial sheets. More than 20 years later, autologous cultivated corneal epithelium and autologous cultivated oral mucosal epithelium products were launched in Japan. In addition, clinical studies of iPS cell-derived corneal epithelial cell sheet transplant have begun, which may solve the issues with conventional autologous epithelial sheets. In corneal endothelium regenerative medicine, a clinical study of transplant of allogenic cultured corneal endothelial cell suspension for bullous keratopathy was reported, in which corneal endothelial cells derived from donor corneas were grown in culture and then injected into the anterior chamber with a ROCK inhibitor (Kinoshita et al. in N Engl J Med 378:995-1003, 2018). Our research group is also developing iPS-cell-derived corneal endothelium-like cells, termed corneal endothelial cell substitute from iPS cells (CECSi cells), and we are conducting a clinical study to treat bullous keratopathy with these cells (Hatou et al. in Stem Cell Res 55:102497, 2021). This review describes the progress and challenges of corneal epithelial and endothelial regenerative medicine and the promising future of corneal regenerative medicine with iPS cells.

Mesenchymal Stem Cells and Regenerative Therapy with Bilateral Gracilis Flaps for Perineal Reconstruction of a Wound Infection in the Setting of Anal Squamous Cell Carcinoma.

Many patients are affected by HIV/AIDS, and these conditions are highly prevalent worldwide. Patients with HIV/AIDS can experience debilitating wound infections that often require flap reconstruction and become challenging for surgeons to treat. In the past 5 years, mesenchymal stem cells have been tested and used as regenerative therapy to promote the growth of tissues throughout the body because of their ability to successfully promote cellular mitogenesis. To the authors' knowledge, the use of mesenchymal stem cell grafting following necrosis of a myocutaneous gracilis flap (as part of perineal wound reconstruction) has never been reported in the literature.In addition, the use of mesenchymal stem cells and regenerative medicine combined in the setting of squamous cell carcinoma of the anus with prior radiation (along with comorbid AIDS) has not been previously documented.In this report, the authors outline the case of a 60-year-old patient who had a recipient bed (perineum) complication from prior radiation therapy. Complicating the clinical picture, the patient also developed a Pseudomonal organ space infection of the pelvis leading to the failure of a vertical rectus abdominis myocutaneous flap and myocutaneous gracilis flaps. As a result, the patient underwent serial operative debridements for source control, with the application of mesenchymal stem cells, fetal bovine dermis, porcine urinary bladder xenograft, and other regenerative medicine products, achieving a highly successful clinical outcome. A procedural description for future use and replication of this method is provided.

Access to clinical trial dossiers and documents submitted for the marketing authorisation of a medicinal product under the provisions on access to public information

This article is devoted to an analysis of the current regulations on the disclosure of clinical trial documentation of a medicinal product and documents submitted for the marketing authorisation of a medicinal product. Undoubtedly, due to the very high commercial value of the data obtained in the course of a clinical trial, the sponsor of such a clinical trial is interested in the widest possible coverage of its business secrecy. On the other hand, however, it is in the interest of patients and the public's health protection at large to have the widest possible access to this information.This article is devoted to an analysis of the current legal provisions on the conduct of clinical trials on medicinal products for human use and the registration of these products, both at EU and Polish level, as well as regulations on access to public information. In order to better illustrate the scale of information that may be covered by a request for access, the scope of documentation created in the course of conducting a clinical trial is also presented.The article also presents the rulings of the Court of Justice of the European Union concerning the scope of the obligation to provide access to this type of documentation and possible exceptions to the general principle of access to all documents processed by EU or national authorities. The purpose of the article is to juxtapose the interests of patients (the widest possible access to data on clinical trials and registration of medicinal products) with the interests of companies conducting clinical trials and to confront the practice of Polish regulators - the President of the Office for Medicinal Products, Medical Devices and Biocidal Products and the European Medicines Agency - with the case-law of the Court of Justice of the European Union in this respect.

Japanese Laws and the Current Status of Regenerative Medicine in the Tohoku Region.

The aim of this study was to review Japanese laws regarding regenerative medicine and the current status of clinical application of regenerative medicine, to learn about the advantages and problems, and to thereby serve as a reference for measures necessary for the development of regenerative medicine. Regenerative medicine started in 1957 with the transplantation of hematopoietic stem cells, followed by the establishment of embryonic stem cells in 1981 and induced pluripotent stem cells in 2006, and continues to evolve progressively. At the same time, however, problems have emerged due to lax legal regulations, such as the use of treatments that lack scientific evidence. The Japanese government enacted two laws to regulate regenerative medicine: the Law to Ensure the Safety of Regenerative Medicine and the Amend the Pharmaceutical Affairs Law in 2013. These laws were enacted with the aim of providing safe regenerative medicine promptly and smoothly and developing many regenerative medicine products. In these laws, regenerative medicine is defined as medical treatment that restores lost functions of damaged organs and tissues with the help of cellular and tissue-based products. Nowadays, there are two major methods of regenerative medicine. One representative method involves the transplantation of devices that activates self-regenerative ability by introducing living cells into patients' body. The other method is the activation and differentiation of endogenous stem cells with cell growth and differentiation factors. The current status of regenerative medicine in the Tohoku region after the enactment of these laws is described in detail. This clarified the advantages and disadvantages associated with regenerative medicine as it is currently practiced in Japan. Development of regenerative medicine in dentistry will be advanced by learning about its clinical application in medicine.