Regenerative Medicine Products Research Articles

Peak MSC-Are We There Yet?

Human mesenchymal stem cells (hMSCs) are a critical raw material for many regenerative medicine products, including cell-based therapies, engineered tissues, or combination products, and are on the brink of radically changing how the world of medicine operates. Their unique characteristics, potential to treat many indications, and established safety profile in more than 800 clinical trials have contributed to their current consumption and will only fuel future demand. Given the large target patient populations with typical dose sizes of 10's to 100's of millions of cells per patient, and engineered tissues being constructed with 100's of millions to billions of cells, an unprecedented demand has been created for hMSCs. The fulfillment of this demand faces an uphill challenge in the limited availability of large quantities of pharmaceutical grade hMSCs for the industry—fueling the need for parallel rapid advancements in the biomanufacturing of this living critical raw material. Simply put, hMSCs are no different than technologies like transistors, as they are a highly technical and modular product that requires stringent control over manufacturing that can allow for high quality and consistent performance. As hMSC manufacturing processes are optimized, it predicts a future time of abundance for hMSCs, where scientists and researchers around the world will have access to a consistent and readily available supply of high quality, standardized, and economical pharmaceutical grade product to buy off the shelf for their applications and drive product development—this is “Peak MSC.”

Too Much Carrot and Not Enough Stick in New Stem Cell Oversight Trends.

Regulators are now more often distinguishing between perceived good citizens and "bad actors" in stem cell and regenerative medicine clinical research, resulting in relatively more polar, carrot-and-stick oversight approaches. Here, I discuss why there may be too much carrot and not enough stick by regulators for effective enforcement.

Regulation of Medicines in Bhutan: Current Status, Challenges and Opportunities

Medicines Regulatory Agencies (MRAs) are responsible for evaluation of quality, safety and efficacy of medicinal products before it is approved for consumption. The regulatory procedures, however, differs from one country to another. Medical products including vaccines, blood and blood products, diagnostics and medical devices are essential for healthcare delivery across the world. The Drug Regulatory Authority (DRA) is an independent national agency for regulation of medicinal products in Bhutan and reports to Bhutan Medicines Board (BMB), the highest policy making body for regulation of medicinal products in the country.
 Medicines Act of the Kingdom of Bhutan is the legal tool for regulation of medicines in Bhutan. Medicinal products are regulated through premarketing and post-marketing control systems. All medicinal products available in the Bhutanese market are registered. DRA regulates all the medicinal products including vaccines, blood products and traditional medicines used for human and veterinary.
 DRA is fully financed by the Government of Bhutan. Bhutan’s medicines regulatory system has evolved over the last one decade. However, as the regulatory mandate continues to increase, DRA is faced with several challenges in terms of human resource, infrastructure and testing laboratory among others. There are also opportunities for the DRA to improve its regulatory capacities to ensure availability of quality and safe medicines for the public.
 Understanding the current practice of medicines regulation in Bhutan can help identify gaps and existing opportunities for improving the regulatory capacity. This article documents the existing practices, challenges and opportunities for regulation of medicinal products in Bhutan.

Concise Review: The Regenerative Journey of Pericytes Toward Clinical Translation.

Coronary artery disease (CAD) is the single leading cause of death worldwide. Advances in treatment and management have significantly improved patient outcomes. On the other hand, although mortality rates have decreased, more people are left with sequelae that require additional treatment and hospitalization. Moreover, patients with severe nonrevascularizable CAD remain with only the option of heart transplantation, which is limited by the shortage of suitable donors. In recent years, cell‐based regenerative therapy has emerged as a possible alternative treatment, with several regenerative medicinal products already in the clinical phase of development and others emerging as competitive preclinical solutions. Recent evidence indicates that pericytes, the mural cells of blood microvessels, represent a promising therapeutic candidate. Pericytes are abundant in the human body, play an active role in angiogenesis, vessel stabilization and blood flow regulation, and possess the capacity to differentiate into multiple cells of the mesenchymal lineage. Moreover, early studies suggest a robustness to hypoxic insult, making them uniquely equipped to withstand the ischemic microenvironment. This review summarizes the rationale behind pericyte‐based cell therapy and the progress that has been made toward its clinical application. We present the different sources of pericytes and the case for harvesting them from tissue leftovers of cardiovascular surgery. We also discuss the healing potential of pericytes in preclinical animal models of myocardial ischemia (MI) and current practices to upgrade the production protocol for translation to the clinic. Standardization of these procedures is of utmost importance, as lack of uniformity in cell manufacturing may influence clinical outcome. Stem Cells 2018;36:1295–1310

FDA and NIST collaboration on standards development activities supporting innovation and translation of regenerative medicine products

The development of standards for the field of regenerative medicine has been noted as a high priority by several road-mapping activities. Additionally, the U.S. Congress recognizes the importance of standards in the 21st Century Cure Act. Standards will help to accelerate and streamline cell and gene therapy product development, ensure the quality and consistency of processes and products, and facilitate their regulatory approval. Although there is general agreement for the need of additional standards for regenerative medicine products, a shared understanding of standards is required for real progress toward the development of standards to advance regenerative medicine. Here, we describe the roles of standards in regenerative medicine as well as the process for standards development and the interactions of different entities in the standards development process. Highlighted are recent coordinated efforts between the U.S. Food and Drug Administration and the National Institute of Standards and Technology to facilitate standards development and foster science that underpins standards development.

Accelerating Cell Therapy for Stroke in Japan

In recent years, the clinical application of regenerative medicine using stem cells has been heralded as a new approach to the treatment of cerebral infarction.1 In Japan, various clinical trials on cell-based products are being initiated in patients with the disease.2,3 However, the full-scale clinical use of such products remains a major challenge. Unsolved questions include how nonclinical studies should be conducted and what type of designs should be used in clinical trials. Similar questions have remained in the United States. Researchers in the academia, industry leaders, and regulatory representatives organized the Stem Cell Therapeutics as an Emerging Paradigm in Stroke (STEPS) program, which proposed basic approaches to quality assurance, nonclinical studies, and clinical trials in the development of cell-based products for the treatment of cerebral infarction.4–6 In Japan, the government has published guidelines for ensuring the quality and safety of individual cell-based products that are used as raw materials. However, no specific guidelines have been established for cell-based products for the treatment of cerebral infarction. Although the STEPS has proposed helpful basic approaches to the development of such regenerative medicine products, guidelines are needed that are based on Japanese regulations, taking into consideration the clinical setting of cerebral infarction treatment in the country.7 Such guidelines would be useful to facilitate appropriate development of the products. For these reasons, we prepared the Guidelines on Development of Cell-based Products for the Treatment of Cerebral Infarction. The guidelines comprised consensus about quality assurance, nonclinical studies, cell delivery methods, and clinical trials on products that were discussed in relevant individual working groups, while considering disease-specific issues and the existing Japanese guidelines on ensuring quality and safety of cell-based products for individual cell types. The original guidelines in Japanese language were framed by Working Group for …

Reklama suplementów diety – analiza prawna

Celem niniejszego artykułu jest analiza prawna reklamy suplementów diety i problemów jakie napotykają konsumenci oraz przedsiębiorcy z uwagi na brak kompleksowego uregulowania przedmiotowych produktów. Nacisk został położony na przeanalizowanie aktów prawnych ustanowionych na poziomie Unii Europejskiej oraz aktów obowiązujących w prawie krajowym, a także przykładach zastosowania powyższych regulacji w orzecznictwie sądów oraz decyzji kompetentnych organów. W obliczu częstych problemów z zastosowaniem się do przepisów właściwych suplementom diety, analiza taka okazuje się niezbędna dla porównania różnych reżimów prawnych rządzących reklamą suplementów diety oraz kompleksowego uregulowania dotyczącego produktów leczniczych.

The Transition of Cellular Medicine Products and Our Future with Regenerative Medicine Products

Everyone wants to stay healthy. Humans have put great effort into researching and developing better medicines and treatment methods in order to promote and maintain their health.

World Integrated Medicine Forum 2017: A feedback survey analysis

Introduction: The first-of-its-kind World Integrated Medicine Forum (WIMF) on the regulation of homoeopathic medicinal products (HMPs) which was attended by various stakeholders from 23 countries witnessed rigorous discussions to strengthen existing regulatory framework of homoeopathic medicines in the world, as well as to bring harmony within the Homoeopathy market for drug manufacture standards including pharmacopoeial convergence. Materials and Methods: A feedback questionnaire was shared with the participants through SurveyMonkey online platform to seek their opinion about the Forum, obtain their country-specific views about regulations of HMPs, to evaluate the extent to which the Forum could meet its objectives and also to identify areas of improvements which may be taken note for organising a future WIMF. Results: Sixty-one percent participants from 18 countries returned the survey. Analysis of the responses revealed a group consensus about the remarkable organisation of the Forum, its usefulness from a national perspective, etc. The questions could also fetch insight about country-specific reforms that are required in the availability and regulations of HMPs. All the respondents who took the survey recommended a next Forum on the same lines, out of which 92% said they would recommend it to other colleagues. Conclusion: Homoeopathy is a widely recognised and accepted system worldwide. Based on its increasing demand, a harmonised regulatory system for homeopathic medicines must be developed to ensure good quality of HMPs, and this can be achieved through cooperative interactions among various stakeholders, both nationally and globally. A Forum such as this, at least once every 2 years, can provide the right push on this front.

ОСОБЛИВОСТІ РЕЄСТРАЦІЇ ЛІКАРСЬКИХ ЗАСОБІВ В УКРАЇНІ

ОСОБЛИВОСТІ РЕЄСТРАЦІЇ ЛІКАРСЬКИХ ЗАСОБІВ В УКРАЇНІ

Medical Applications of Collagen and Hyaluronan in Regenerative Medicine.

In order to develop and commercialize for the regenerative medicinal products, smart biomaterials with biocompatibility must be needed. In this chapter, we introduce collagen and hyaluronic acid (HA) as extracellular matrix as well as deal with the molecular mechanism as microenvironment, mechanistic effects, and gene expression. Application of collagen and HA have been reviewed in the area of orthopedics, orthopedics, ophthalmology, dermatology and plastic surgery. Finally, the ongoing and commercial products of collagen and HA for regenerative medicine have been introduced.

Regulation of Regenerative Medicine Products.

Cellular therapies have moved to the forefront based upon promising results from clinical trials using both chimeric antigen receptor T lymphocytes to treat leukemia and other cell types to restore structure and function to tissues that have been damaged by disease or physical injury. The pace at which these treatments have evolved has posed a regulatory challenge to agencies, such as the Food and Drug Administration (FDA). This chapter describes how a specific regulatory strategy was developed and how it has evolved in response to the demand for these new therapies.

Neural stem/progenitor cells maintained in vitro under different culture conditions alter differentiation capacity of monocytes to generate dendritic cells

Cell therapy of the nervous system disorders using neural stem/progenitor cells (NSPCs) proved its efficacy in preclinical and pilot clinical studies. The mechanisms of the beneficial effects of NSPCs transplantation include replacement of damaged cells, paracrine activation of the regeneration, and immunomodulation. Detailed assessment of NSPCs-induced immunomodulation can contribute to better control of autoimmune reactions and inflammation in patients with neurodegenerative diseases. Interactions of NSPCs with dendritic cells (DCs), the key players in the induction of the immune system response to antigens are of particular interest. Here, we demonstrate that co-culturing of monocytes with NSPCs obtained and grown utilizing serum-containing medium instead of growth factor-containing serum-free medium, results in total suppression of monocyte differentiation into DCs. The effect is similar to the action of mesenchymal stem cells (MSCs). No significant effect on DCs maturation was observed. Cultures of NSPCs set up and maintained in serum-free medium have no influence on monocyte differentiation and DCs maturation. Therefore, the effects of NSPCs upon DC differentiation from monocytes strongly depend on culture conditions, whereas the molecular marker expression patterns are similar in both types of NSPCs cultures. In broader prospective, it means that cells with almost identical phenotypes can display opposite immunological properties depending upon culture conditions. It should be taken into account when developing NSPCs-based cell products for regenerative medicine.

Faecal microbiota transplantation: a regulatory hurdle?

During faecal microbiota transplantation, stool from a healthy donor is transplanted to treat a variety of dysbiosis-associated gut diseases. Competent authorities are faced with the challenge to provide adequate regulation. Currently, regulatory harmonization is completely lacking and authorities apply non-existing to most stringent requirements. A regulatory approach for faecal microbiota transplantation could be inserting faecal microbiota transplantation in the gene-, cell- and tissue regulations, including the hospital exemption system in the European Advanced Therapy Medicinal Products regulation, providing a pragmatic and efficacy-risk balanced approach and granting all patients as a matter of principle access to this therapy.

Challenges of running a GMP facility for regenerative medicine in a public hospital.

Advanced therapy medicinal products represent a new generation of medicinal products for regenerative medicine. Since the implementation of the EU regulation for this innovative class of drugs, the academic and hospital institutions have played a central role in their development and manufacture. For these institutions that are not familiar with the industrial context, being in compliance with the pharmaceutical standards is extremely challenging. This report describes how we dealt with some specific issues during our hospital-based GMP experience. Furthermore, we identify as a future perspective the consistent stimulating contribution that a public entity can ensure for advanced therapy medicinal product development and licensing.

The unique characteristics of regulations and clinical practice to be considered in developments of regenerative medicine products in Japan

The unique characteristics of regulations and clinical practice to be considered in developments of regenerative medicine products in Japan

Novel Tenascin-C Haplotype Modifies the Risk for a Failure to Heal After Rotator Cuff Repair

Background: Several single-nucleotide polymorphisms (SNPs) in the TNC gene have recently been found to be associated with degenerative rotator cuff tears. Hypothesis: Exonic SNPs in the TNC gene are related to the risk for a failure to heal after rotator cuff repair. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 302 patients from the Vienna area and European Caucasian ancestry underwent mini-open rotator cuff repair for a full-thickness superior or posterosuperior tear and were assessed for the integrity of the repair 1 year postoperatively with a real-time 7.5- to 10-MHz ultrasound linear array transducer. Outcomes were classified as intact (complete footprint coverage), small (<200 mm2), or large (≥200 mm2) recurrent defect. Patients were genotyped for 15 previously identified risk SNPs within a 49-kbp segment of the TNC gene with the KASP genotyping technology or the Ion-Torrent Personal Genome Machine System. Results: All recurrent defects were atraumatic failures, and the overall failure rate was 39.7%. Of the traditional risk factors, only the initial tear size was significantly associated with a failure to heal. In a multinomial logistic regression model, the T allele at rs1138545 [C>T] was protective for a large recurrent defect (odds ratio = 0.16; 95% CI, 0.09-0.31). The role of rs1138545 was further backed by haplotype analysis, which showed that the combination of the C allele at rs1138545 [C>T], the A allele at rs2104772 [A>T], and the G allele at rs10759752 [A>G] formed the risk-related haplotype [CAG]. The CAG haplotype was associated with large recurrent defects (P < .0001; haplotype frequency, 0.394; haplotype score, 4.518). Exonic marker rs1138545 transcribed into all isoforms of the TNC protein, whereas exonic marker rs2104772, which has been associated with Achilles tendinopathy before, transcribed only into large isoforms of the TNC protein. Conclusion: Recurrent defects after rotator cuff repairs are clinically relevant, and a heritable component of the disorder is plausible on the basis of a genetic association with 8 TNC variants. Characterization of TNC sequences that favor tendon healing will help engineer new products in regenerative medicine.

The emerging landscape of reimbursement of regenerative medicine products in the UK: publications, policies and politics.

This paper aims to map the trends and analyze key institutional dynamics that constitute the policies for reimbursement of regenerative medicine (RM), especially in the UK. Two quantitative publications studies using Google Scholar and a qualitative study based on a larger study of 43 semi-structured interviews. Reimbursement has been a growing topic of publications specific to RM and independent from orphan drugs. Risk-sharing schemes receive attention among others for dealing with RM reimbursement. Trade organizations have been especially involved on RM reimbursement issues and have proposed solutions. The policy and institutional landscape of reimbursement studies in RM is a highly variegated and conflictual one and in its infancy.

Accelerating regenerative medicine: the Japanese experiment in ethics and regulation.

In 2014, the Japanese National Diet introduced new laws aimed at promoting the clinical translation of stem cells and regenerative medicine. The basic action of these laws is to allow the early introduction of regenerative medicine products into the Japanese market through an accelerated approval process, while providing patients with access to certain types of stem cell and cell-based therapies in the context of private clinical practice. While this framework appears to offer enormous opportunities for the translation of stem cell science, it raises ethical challenges that have not yet been fully explored. This paper critically analyzes this framework with respect to the prioritization of safety over clinical benefit, distributive justice and public trust in science and medicine. It is argued that the framework unfairly burdens patients and strained healthcare systems without any clear benefits, and may undermine the credibility of the regenerative medicine field as it emerges.

Human resource development contributes to the creation of outstanding regenerative medicine products.

Regenerative medicine is currently the focus of global attention. Countries all around the world are actively working to create new regenerative treatment modalities through pioneering research and novel technologies. This is wonderful news for patients who could not be treated with existing medical options. New venture businesses and companies are being established in regenerative medicine and their rapid industrialization is anticipated. However, to ensure high-quality products, human resources qualified in research and development and the manufacturing of these products are essential. The Forum for Innovative Regenerative Medicine (FIRM) conducted a questionnaire of its industry members to examine the training and hiring of people in research and development, product creation, manufacturing, and more. Regenerative medicine is a brand new field; thus, many different businesses will need to cooperate together. People with a broad range of technical skills, abilities, and knowledge will be in demand, with various levels of expertise, from basic to advanced.