• cell therapy
• ethical concerns
• exosomes
• extracellular vesicles
• mitochondrial dysfunction
• mitochondrial medicine
• neurodegenerative diseases
• stem cells

• R21 NS128751 NINDS NIH HHS

• advanced therapies
• autologous cell-based therapy
• cell therapy
• clinical trial ethics
• health product regulation
• healthcare providers
• patient education
• patient experience
• pay-to-participate trials
• regenerative medicines
• stem cell regulation
• stem cells

• Humans
• Male
• Cell- and Tissue-Based Therapy/ethics
• Cell- and Tissue-Based Therapy/methods
• Adult
• Transplantation, Autologous
• Middle Aged
• Female
• Surveys and Questionnaires
• Aged
• Perception
• Young Adult
• Adolescent

• clinical application
• regenerative medicine
• standardisation
• stem cell therapy

• Humans
• Stem Cell Transplantation
• Reference Standards

• 2022JJ12SN045 Science and Technology Innovation Foundation of Dalian
• 2022-MS-322 Natural Science Foundation of Liaoning Province
• Natural Science Foundation of Liaoning Province

• fat
• inflammation
• injury
• neuroprotection
• paraplegia
• reflex
• sensorimotor

• Humans
• Rats
• Male
• Animals
• Sodium Chloride
• Rats, Sprague-Dawley
• Spinal Cord Injuries/therapy
• Adipose Tissue
• Contusions/therapy
• Inflammation

• 00976-NeuroStem-2021-09 NeuroGel en Marche Association

• Extracellular vesicles (EV)
• Inflammaging
• Mesenchymal stem cells (MSC)
• Senescence-associated secretory phenotype (SASP)
• Syndecan-1 (SDC1)
• miR-21-5p (miR-21)

• Humans
• Proteomics
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Inflammation/metabolism
• Extracellular Vesicles/metabolism
• Mesenchymal Stem Cells/metabolism

• ED481D-2021-020. Xunta de Galicia
• 11_IN858A_2021_1141142 Xunta de Galicia
• PI20/00497 Instituto de Salud Carlos III

• Stem Cell Research
• Translational Research, Biomedical

• K23 AI157875 NIAID NIH HHS
• L30 AI147159 NIAID NIH HHS
• UM1 AI164560 NIAID NIH HHS

• Diabetic wounds
• Exosomes
• Mesenchymal stem cells
• Pre-conditioning
• Preclinical translation
• Wound and injuries

• bio-artificial organs
• bioengineering
• clinical trials
• early-phase clinical trials
• ethics
• first-in-human clinical trials
• regenerative medicine
• research ethics

Biomaterials--from implanted iron teeth in the second century to intraocular lenses, artificial joints, and stents today--have long been used clinically. Today, biomaterials researchers and biomedical engineers are pushing beyond these inert synthetic alternatives and incorporating complex multifunctional materials to control biological interactions and direct physiological processes. These advances are leading to novel strategies for targeted drug delivery, drug screening, diagnostics and imaging, gene therapy, tissue regeneration, and cell transplantation. While the field has survived ethical transgressions in the past, the rapidly expanding scope of biomaterials science, combined with the accelerating clinical translation of this diverse field calls for urgent attention to the complex and challenging ethical dilemmas these advances pose. This perspective responds to this call, examining the intersection of research ethics -- the sets of rules, principles and norms guiding responsible scientific inquiry -- and ongoing advances in biomaterials. While acknowledging the inherent tensions between certain ethical norms and the pressures of the modern scientific and engineering enterprise, we argue that the biomaterials community needs to proactively address ethical issues in the field by, for example, updating or adding specificity to codes of ethics, modifying training programs to highlight the importance of ethical research practices, and partnering with funding agencies and journals to adopt policies prioritizing the ethical conduct of biomaterials research. Together these actions can strengthen and support biomaterials as its advances are increasingly commercialized and impacting the health care system.

• National Science Foundation

• Aspirational ethics
• Biostatistician
• Research governance
• Standard of conduct
• Stem cell researcher
• Virtue ethics

• Ethics, Professional
• Motivation
• Stem Cells

• JSPS KAKENHI
• Ministry of Health, Labour and Welfare
• Uehiro Foundation on Ethics and Education

• Attitude of Health Personnel
• Cross-Sectional Studies
• Female
• Health Knowledge, Attitudes, Practice
• Humans
• Jordan
• Male
• Physicians
• Reproducibility of Results
• Stem Cells
• Surveys and Questionnaires

• Sendai viral reprogramming
• episomal reprogramming
• human induced pluripotent stem cells (hiPSCs)
• reprogramming

The International Society for Stem Cell Research has updated its Guidelines for Stem Cell Research and Clinical Translation in order to address advances in stem cell science and other relevant fields, together with the associated ethical, social, and policy issues that have arisen since the last update in 2016. While growing to encompass the evolving science, clinical applications of stem cells, and the increasingly complex implications of stem cell research for society, the basic principles underlying the Guidelines remain unchanged, and they will continue to serve as the standard for the field and as a resource for scientists, regulators, funders, physicians, and members of the public, including patients. A summary of the key updates and issues is presented here.

The ISSCR’s revised Guidelines for Stem Cell Research and Clinical Translation reflect the organization’s commitment to opposing premature commercialization of stem cell-based interventions and supporting the development of products that meet stringent ethical, scientific, and regulatory standards. The Guidelines contain five important new recommendations concerning clinical translation of stem cell products.

• ethics
• evidence
• physician perspectives
• qualitative research
• responsible translation
• unproven stem cell interventions

No effective treatment is currently available for neurodegenerative diseases, and existing pharmacotherapy is inconsistent with severe side effects. Cell replacement therapy is promising for neurodegenerative disease treatment, and the induction of neurons is an unmet need for such therapy. The present study investigated the potential of a combined medium composed of conditioned medium and eight small molecular compounds in reprogramming human foreskin fibroblasts (HFFs) into neurons. HFFs were cultured from foreskin and then induced by small molecules to generate neurons. The results demonstrated that the conditioned medium containing forskolin, RepSox, SP600125, CHIR99021, Go6983, Y-27632, IXS9 and I-BET151 effectively induced human fibroblasts to change into neurons in vitro. Following a 30-day induction, the cells exhibited neuronal properties as determined by morphological and phenotypical alterations. The induced cells exhibited expression of neuronal markers, including class III β-tubulin, microtubule-associated protein 2, vesicular glutamate transporter 1 and γ-aminobutyric acid, accompanied by increased expression of neuronal transcription factors, including neuronal differentiation 1 and achaete-scute family bHLH transcription factor 1, and decreased expression levels of fibroblast-specific genes. Furthermore, these cells also exhibited electrophysiological properties of neurons. Notably, the course of cell morphological alterations demonstrated the differentiation of fibroblasts into neurons. The present study provided a novel combination of existing small molecular compounds that efficiently reprogramed human fibroblasts into neurons.

Although a large body of information exists relating to cellular therapies, much of this information is either anecdotal or has been obtained from relatively small clinical trials, so that the level of evidence available to direct adoption of therapeutic approaches is quite limited. Despite this, a large number of clinics offer various cellular treatments without having gone through the processes of FDA approval. Florida is considered a “hotspot” of such sites, with a large number of clinics relative to the population.

To better understand the magnitude and scope of this issue with a specific focus on cardiovascular disease, we surveyed clinics in Florida advertising “cell therapy for heart failure”. We identified only 8 clinics that “treat cardiac conditions, including heart failure.” Data on administration route, cell type used, dose, success rate, cost, and training of persons performing procedures were collected when available, via email, telephone, or website information.

A total of 20,135 patients were identified as treated: 2157 for cardiac conditions. All clinics reported administering cells intravenously, using either adipose- or umbilical-derived sources. Doses ranged from 30 to 150 million cells per treatment. The “success rate” ranged from 65 to 85%, with costs from $6000 to $20,700. Procedures were performed by PAs, MDs, and DOs.

Large numbers of patients (> 10% of all 20,135 patients) have been and presumably are still are being treated for “cardiac conditions.” We conclude that implementation of uniform data collection with an outcome registry, as well as creation of a public database listing FDA-approved cell-based clinical trials, would be useful to patients and the cardiovascular field at large.

• Adipose stem cell
• Cardiovascular disease
• Cell therapy
• Heart failure
• Stem cell

Despite years of warnings by the academic community that for most of the stem cell-based therapies offered in the private arena little evidence of efficacy exists, these services have been increasingly offered by Canadian private clinics. Recently, as the culmination of years of clashes between stem cell researchers and therapy providers, Health Canada issued a statement prohibiting any type of cell therapy that is not specifically approved. In this climate of conflict, a small group representing both these communities as well as the government gathered in Vancouver to identify common values, and agree on principles to move forward constructively. This historic moment demonstrated that even in this contentious space a meeting-of-minds in between researchers, clinicians, ethicists, entrepreneurs and other stakeholders is possible.

• Clinical
• Ethics
• Health policy
• Medicine and the law
• Stem cell therapies

For decades, stem cells and their byproducts have shown efficacy in repairing tissues and organs in numerous pre-clinical studies and some clinical trials, providing hope for possible cures for many important diseases. However, the translation of stem cell therapy for heart diseases from bench to bed is still hampered by several limitations. The therapeutic benefits of stem cells are mediated by a combo of mechanisms. In this review, we will provide a brief summary of stem cell therapies for ischemic heart disease. Basically, we will talk about these barriers for the clinical application of stem cell-based therapies, the investigation of mechanisms behind stem-cell based cardiac regeneration and also, what bioengineers can do and have been doing on the translational stage of stem cell therapies for heart repair.

• Stem cell therapy
• bioengineering strategies
• clinical translation
• ischemic heart diseases

• Animals
• Cell Engineering
• Cell- and Tissue-Based Therapy/methods
• Humans
• Mesenchymal Stem Cells/cytology
• Neoplasms/pathology
• Neoplasms/therapy
• Translational Research, Biomedical

• R01 EB022558 NIBIB NIH HHS

• CRISPR
• Gene editing
• embryo ethics
• genetic and ethics
• governance
• research ethics

• Acute paraplegia
• Cellular interventions
• Clinical trial
• Guidelines
• Position statement
• Regulations
• Spinal cord injury
• Stem cell

Spinal cord injury (SCI) is a devastating disease, which leads to paralysis and is associated to substantially high costs for the individual and society. At present, no effective therapies are available. Here, the use of mechanically-activated lipoaspirate adipose tissue (MALS) in a murine experimental model of SCI is presented. Our results show that, following acute intraspinal MALS transplantation, there is an engraftment at injury site with the acute powerful inhibition of the posttraumatic inflammatory response, followed by a significant progressive improvement in recovery of function. This is accompanied by spinal cord tissue preservation at the lesion site with the promotion of endogenous neurogenesis as indicated by the significant increase of Nestin-positive cells in perilesional areas. Cells originated from MALS infiltrate profoundly the recipient cord, while the extra-dural fat transplant is gradually impoverished in stromal cells. Altogether, these novel results suggest the potential of MALS application in the promotion of recovery in SCI.

• adipose tissue
• cell therapies
• inflammation
• mechanical activation
• neurogenesis
• neuroprotection
• spinal cord injury

New health technologies are rapidly emerging from various areas of bioscience research, such as gene editing, regenerative medicine and synthetic biology. These technologies raise promising medical possibilities but also a range of ethical considerations. Apart from the issues involved in considering whether novel health technologies can or should become part of mainstream medical treatment once established, the process of research translation to develop such therapies itself entails particular ethical concerns. In this paper I use synthetic biology as an example of a new and largely unexplored area of health technology to consider the ways in which novel health technologies are likely to emerge and the ethical challenges these will present. I argue that such developments require us to rethink conventional attitudes towards clinical research, the roles of doctors/researchers and patients/participants with respect to research, and the relationship between science and society; and that a broader framework is required to address the plurality of stakeholder roles and interests involved in the development of treatments based on novel technologies.

• Experimental therapy
• Health technology
• Medical innovation
• Research ethics
• Research translation
• Synthetic biology

• Parkinson's disease
• cell therapy
• dopaminergic neuron
• embryonic stem cell
• monkey
• nonhuman primate

• Animals
• Behavior, Animal
• Biomarkers
• Brain/cytology
• Brain/metabolism
• Cell Differentiation
• Cell Line
• Cell Movement
• Cell Survival
• Cell Transformation, Neoplastic
• Cell- and Tissue-Based Therapy
• Disease Models, Animal
• Dopamine/metabolism
• Dopaminergic Neurons/cytology
• Dopaminergic Neurons/physiology
• Embryonic Stem Cells/cytology
• Humans
• Locomotion
• Neural Stem Cells/cytology
• Neural Stem Cells/metabolism
• Parkinson Disease/etiology
• Parkinson Disease/physiopathology
• Parkinson Disease/therapy
• Phenotype
• Primates
• Putamen/metabolism
• Putamen/physiopathology

Direct to consumer offerings of unproven stem cell interventions (SCIs) is a pressing scientific and policy issue. According to media reports, providers of SCIs have emerged in Canada. This study provides the first systematic scan of Canadian providers and associated trends and claims.

The study sample consisted of 15 websites retrieved from a Google™ keyword search. The websites were assessed by a rater using a peer-reviewed coding frame that queried treatment location, stem cell offerings, treatment claims, supporting evidence, and legal and regulatory compliance. A second rater reviewed a subset of the websites for purposes of inter-rater reliability. Disagreements between raters were resolved by consensus. Data collected by the raters was analyzed in SPSS.

Physicians are the dominant treatment providers in Canada. Providers operate in urban and semi-urban areas in the most populous provinces. SCIs provided are mainly autologous adult stem cells for multiple conditions including musculoskeletal disorders, spinal cord injury (SCI) and diabetes. Efficacy and benefits of treatment are prominently and positively portrayed, while risks are not mentioned or portrayed as trivial. Regulatory concerns are not discussed.

The involvement of physicians in promoting and providing unproven and unapproved SCIs raises significant ethical, legal and regulatory concerns. Treatment claims and trends appear to contravene applicable professional standards, statutory obligations, and consumer protection laws. While the number of providers observed is still marginal, urgent and proactive regulatory response is needed to prevent proliferation of a potentially exploitative and harmful market for unproven SCIs in Canada.

The online version of this article (10.1186/s12910-018-0273-6) contains supplementary material, which is available to authorized users.

• Canada
• False advertising
• Physicians
• Stem cell
• Stem cell interventions (SCIs)
• Stem cell tourism
• Stem cell treatment
• Unproven treatments

• health assessment
• preclinical
• mar
• offspring
• transgenerational inheritance
• dohad

• Female
• Follow-Up Studies
• Humans
• Infant, Newborn
• Longitudinal Studies
• Pregnancy
• Pregnancy Outcome
• Prospective Studies
• Reproductive Techniques, Assisted/adverse effects
• Research Design

• Adult
• Animals
• Bone Marrow Transplantation/legislation & jurisprudence
• Bone Marrow Transplantation/methods
• Burns/surgery
• Burns/therapy
• Clinical Trials as Topic
• Cost-Benefit Analysis/statistics & numerical data
• Embryonic Stem Cells/transplantation
• Epidermis/transplantation
• Genetic Therapy/economics
• Genetic Therapy/methods
• Health Services Accessibility/standards
• Health Systems Agencies/economics
• Health Systems Agencies/legislation & jurisprudence
• Hematologic Diseases/surgery
• Hematologic Diseases/therapy
• Humans
• Induced Pluripotent Stem Cells/transplantation
• Models, Animal
• Regenerative Medicine/economics
• Regenerative Medicine/legislation & jurisprudence
• Regenerative Medicine/trends
• Stem Cell Research/ethics
• Stem Cells/physiology
• Therapies, Investigational/ethics
• Tissue Engineering/economics
• Tissue Engineering/legislation & jurisprudence
• Tissue Engineering/trends

• MR/K026453/1 Medical Research Council
• RP_2014-04-046 Department of Health
• Wellcome Trust
• MR/P016006/1 Medical Research Council
• G1001539 Medical Research Council
• PG/14/1/30549 British Heart Foundation

• cholinergic neuron
• human brain vascular pericytes
• neurodegenerative disease
• reprogramming
• transcription factors

• Ethics
• Governance
• Guardianship
• Harmonization
• Regulation
• Standardization
• Stem cell banks

• Animals
• Biological Specimen Banks/ethics
• Biological Specimen Banks/standards
• Humans
• Stem Cells/cytology

• adipose tissue
• gene activation
• inflammation
• mechanical activation
• mesenchymal stem cells

• Adipogenesis
• Adipose Tissue/cytology
• Anti-Inflammatory Agents/metabolism
• Cell Separation
• Cells, Cultured
• Cytokines/genetics
• Cytokines/metabolism
• Gene Expression Regulation
• Humans
• Lipectomy
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Osteogenesis
• Pluripotent Stem Cells/metabolism
• Stress, Mechanical

We previously showed the efficacy of multiple research cell lines (RCLs) of human CNS neural stem cells (HuCNS-SCs) in mouse and rat models of thoracic spinal cord injury (SCI), supporting a thoracic SCI clinical trial. Experts recommend in vivo preclinical testing of the intended clinical cell lot/line (CCL) in models with validity for the planned clinical target. We therefore tested the efficacy of two HuCNS-SC lines in cervical SCI: one RCL, and one CCL intended for use in the Pathway Study of cervical SCI in man. We assessed locomotor recovery and sensory function, as well as engraftment, migration, and fate. No evidence of efficacy of the CCL was observed; some data suggested a negative impact of the CCL on outcomes. These data raise questions about the development and validation of potency/comparability assays for clinical testing of cell products, and lack of US Food and Drug Administration requirements for in vivo testing of intended clinical cell lines.

•

Human CNS stem cells (HuCNS-SCs) have been used in multiple clinical trials

• FDA guidelines for cell therapies
• RIGOR
• cervical
• efficacy
• good manufacturing practices (GMP)
• human neural stem cells (hNSC)
• spinal cord injury (SCI)

• clinical trials
• medical ethics
• multiple sclerosis and neuroinflammation
• remyelination
• stem cells

• Hematopoietic Stem Cell Transplantation/methods
• Humans
• Induced Pluripotent Stem Cells/transplantation
• Mesenchymal Stem Cell Transplantation/methods
• Multiple Sclerosis/therapy
• Myelin Sheath
• Oligodendroglia
• Regeneration
• Stem Cell Transplantation/methods
• Stem Cells
• Transplantation, Autologous

• G0300336 Medical Research Council
• G0802545 Medical Research Council
• MC_PC_12009 Medical Research Council
• MR/K004166/1 Medical Research Council

• Barriers to regeneration after SCI
• Bone marrow
• Cellular interventions
• Clinical evidence
• Clinical trials
• Mesenchymal stem cells
• Preclinical evidence
• Unproven therapies

• ethics
• regenerative medicine
• regulation
• research translation
• stem cells

• Bioethics
• Health Services Accessibility
• Humans
• Internationality
• Marketing of Health Services
• Medical Tourism
• Patient Rights
• Regenerative Medicine/ethics
• Stem Cell Transplantation/ethics
• Translational Research, Biomedical/ethics

• Wellcome Trust
• 204403/Z/16 Wellcome Trust

• PBBI
• TBI
• behavior deficit
• cell transplantation
• hNSC
• neuronal differentiation

• Animals
• Brain Injuries, Traumatic/diagnosis
• Brain Injuries, Traumatic/therapy
• Cell Differentiation/physiology
• Cognition Disorders/diagnosis
• Cognition Disorders/therapy
• Head Injuries, Penetrating/diagnosis
• Head Injuries, Penetrating/therapy
• Humans
• Neural Stem Cells/transplantation
• Neurons/physiology
• Random Allocation
• Rats
• Rats, Inbred F344
• Rats, Nude
• Rats, Sprague-Dawley
• Stem Cell Transplantation/methods

• F32 NS041710 NINDS NIH HHS
• R25 NS083064 NINDS NIH HHS

Human embryonic stem cells (hESCs) are promising in regenerative medicine. Although several hESC-based clinical trials are under way, a widely accepted standard of clinical-grade cells remains obscure. To attain a completely xeno-free clinical-grade cell line, the system must be free of xenogenic components, the cells must have a comprehensive set of functions, and good manufacturing practice conditions must be used. In this study, following these criteria, we successfully derived two hESC lines, which were thereby considered “clinical-grade embryonic stem cells”. In addition to the primary capacity for pluripotency, these two cell lines were efficiently differentiated into various types of clinical-grade progeny. Importantly, the cells were recognized by the National Institutes for Food and Drug Control of China for further eligible accreditation. These data indicate that we have established completely xeno-free clinical-grade hESC lines and their derivatives, which will be valuable for the foundation of an international standard for clinical-grade cells for therapy.

•

Two clinical-grade hESC lines were generated

• biosafety
• chemically defined
• clinical-grade hESCs
• functional differentiation
• xeno-free

Neurologists in their clinical practice are faced with inquiries about the suitability of stem cell approaches by patients with a variety of acute and chronic (namely neurodegenerative) disorders. The challenge is to provide these patients with accurate information about the scope of stem cell use as well as at the same time, empowering patients with the capacity to make an autonomous decision regarding the use of stem cells.

The Indian Academy of Neurology commissioned an Expert Group Meeting to formulate an advisory to practicing neurologists to counsel patients seeking information and advice about stem cell approaches.

In the course of such counselling, it should be emphasized that the information provided by many lay websites might be unsubstantiated. Besides, standard recommendations for the stem cell research, in particular, the application of several layers of oversight should be strictly adhered in order to ensure safety and ethical use of stem cells in neurological disorders.

• Cerebellar ataxias
• Parkinson's disease
• motor neuron disease
• multiple sclerosis
• muscle disorders
• neurological disorders
• spinal cord injury
• stem cells
• stroke