Regenerative Medicine Products Research Articles

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.

Degradation of oligo[poly(ethylene glycol) fumarate] hydrogels through stimulus-mediated pendent group cyclization

Hydrogels are of interest for a wide range of applications including drug delivery, regenerative medicine, agriculture, and personal care products. Among the water-soluble synthetic polymers that can be processed to form hydrogels, oligo[poly(ethylene glycol) fumarate] (OPF) has attracted significant attention. The degradation of OPF can be tuned to some extent based on the poly(ethylene glycol) chain length and amount of cross-linker incorporated, but the degradation is generally quite slow, occurring over several months. Here we introduce a new approach to tune and trigger the degradation of OPF. Fumarate alkenes were functionalized to introduce protected pendent amines, that after deprotection could cyclize to 6-membered lactams, thereby cleaving the polymer backbone. Using light as a model stimulus, we demonstrated that the cleavage of an o-nitrobenzyl carbamate protecting group led to more rapid polymer degradation. Remaining unfunctionalized fumarates allowed the functionalized OPF to be cross-linked, forming a hydrogel. Treatment with light led to breakdown of the hydrogels, as indicated by a substantial reduction in the compressive modulus. The functionalization and stimulus-responsive cleavage mechanism should be applicable to other stimuli, providing a versatile approach to control OPF degradation for various applications.

PD19-03 THE DELIVERY OF THE RECOMBINANT PROTEIN COCKTAIL IDENTIFIED BY STEM CELL-DERIVED SECRETOME ANALYSIS ACCELERATES KIDNEY REPAIR AFTER RENAL ISCHEMIA-REPERFUSION INJURY

You have accessJournal of UrologyCME1 Apr 2023PD19-03 THE DELIVERY OF THE RECOMBINANT PROTEIN COCKTAIL IDENTIFIED BY STEM CELL-DERIVED SECRETOME ANALYSIS ACCELERATES KIDNEY REPAIR AFTER RENAL ISCHEMIA-REPERFUSION INJURY Ji Hyun Kim, Heejo Yang, Michael Kim, Kang Su Cho, Doo Sang Kim, Hyung Eun Yim, Zachary Atala, John Jackson, In Kap Ko, and James Yoo Ji Hyun KimJi Hyun Kim More articles by this author , Heejo YangHeejo Yang More articles by this author , Michael KimMichael Kim More articles by this author , Kang Su ChoKang Su Cho More articles by this author , Doo Sang KimDoo Sang Kim More articles by this author , Hyung Eun YimHyung Eun Yim More articles by this author , Zachary AtalaZachary Atala More articles by this author , John JacksonJohn Jackson More articles by this author , In Kap KoIn Kap Ko More articles by this author , and James YooJames Yoo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003285.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Renal disease is a worldwide health issue. Stem cell therapies have been proposed to restore damaged kidneys as an alternative to renal replacement therapies. In addition to stem cell therapies, recent studies have shown that stem cell-derived secretomes or conditioned media (CM) can enhance tissue regeneration. Our previous study demonstrated that the controlled delivery of human placental stem cells (hPSC)-derived CM using platelet-rich plasma (PRP) improved histological and functional recovery in an acute kidney injury (AKI) model in rats. The protein analysis of hPSC-CM showed the five highly expressed proteins that promote kidney repair. Based on our results, we propose that these proteins could be used as a recombinant protein cocktail to treat kidney diseases as an alternative to using CM. This study investigated the feasibility of delivering the recombinant protein cocktail for kidney repair after AKI. METHODS: The effects of the recombinant protein cocktail on human renal cell survival, proliferation, and apoptosis were compared with the CM in vitro. The feasibility of delivering the recombinant protein cocktail with a PRP system to achieve structural and functional recovery after AKI was investigated. RESULTS: The pro-proliferative and anti-apoptotic effects of the protein cocktail on renal cells were demonstrated in vitro and in vivo. The intrarenal delivery of these proteins with PRP ameliorates the renal tubular damage and improved renal function in the AKI-induced rats, yielding similar therapeutic effects compared to the CM delivery. CONCLUSIONS: The delivery of RPC can support renal cell survival and proliferation in vitro and in vivo, resulting in the attenuation of renal tubular damages and amelioration of renal function in the AKI model in rats. Our strategy may provide a therapeutic solution to many challenges associated with kidney repair resulting from the lack of suitable off-the-shelf regenerative medicine products. Source of Funding: This work was supported by the State of North Carolina © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e577 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ji Hyun Kim More articles by this author Heejo Yang More articles by this author Michael Kim More articles by this author Kang Su Cho More articles by this author Doo Sang Kim More articles by this author Hyung Eun Yim More articles by this author Zachary Atala More articles by this author John Jackson More articles by this author In Kap Ko More articles by this author James Yoo More articles by this author Expand All Advertisement PDF downloadLoading ...

Drug Regulatory Affairs: Short Review

Drug regulatory affairs are an important part of the pharmaceutical industry. As usual The pharmaceutical industry is growing very fast, and there is a need Regulatory affairs experts to meet current needs industry for global competition. Drug Regulatory Affairs Specialists are an important link between the pharmaceutical industry And regulatory agencies around the world. Drug product approval Should be an important step to ensure that the process is safe and effective Drug. Central Narcotics Control Organization (CDSCO), India Decided to adopt the CTD format for the technical requirements for Registration of medicinal products for human use. Implementation CTD is expected to significantly reduce the time and resources required By industry to prepare applications for global registration. In this article Evolution of Drug Regulatory Issues, Roles and Relationships in the Pharmaceutical Industry to implement CTD guidelines to regulate and improve drug marketing industrial development

Growth of mesenchymal stem cells at the surface of silicone, mineral and plant-based oils

Bioemulsions are attractive platforms for the expansion of adherent cells in bioreactors. Their design relies on the self-assembly of protein nanosheets at liquid–liquid interfaces, displaying strong interfacial mechanical properties and promoting integrin-mediated cell adhesion. However, most systems developed to date have focused on fluorinated oils, which are unlikely to be accepted for direct implantation of resulting cell products for regenerative medicine, and protein nanosheets self-assembly at other interfaces has not been investigated. In this report, the composition of aliphatic pro-surfactants palmitoyl chloride and sebacoyl chloride, on the assembly kinetics of poly(L-lysine) at silicone oil interfaces and characterisation of ultimate interfacial shear mechanics and viscoelasticity is presented. The impact of the resulting nanosheets on the adhesion of mesenchymal stem cells (MSCs) is investigated via immunostaining and fluorescence microscopy, demonstrating the engagement of the classic focal adhesion-actin cytoskeleton machinery. The ability of MSCs to proliferate at the corresponding interfaces is quantified. In addition, expansion of MSCs at other non-fluorinated oil interfaces, based on mineral and plant-based oils is investigated. Finally, the proof-of-concept of such non-fluorinated oil systems for the formulation of bioemulsions supporting stem cell adhesion and expansion is demonstrated.

Clinical trials in the Eurasian Economic Union

In January 2021, the single market of medicines of the Eurasian Economic Union (EAEU) was launched. This article describes the current status of the transition to unified rules for the registration of medicinal products and the main regulatory documents for conducting clinical trials in the EAEU region.