Regulatory capacity building and the governance of clinical stem cell research in China

While other works have explained difficulties in applying ‘international’ guidelines in the field of regenerative medicine in so-called low- and middle-income countries (LMICs) in terms of ‘international hegemony’, ‘political and ethical governance’ and ‘cosmopolitisation’, this article on stem cell regulation in China emphasises the particular complexities faced by large LMICs: the emergence of alternative regulatory arrangements made by stakeholders at a provincial level at home. On the basis of ethnographic and archival research of clinical stem cell research hubs, we have characterized six types of entrepreneurial ‘bionetworks’, each of which embodies a regulatory orientation that developed in interaction with China’s regulatory dilemmas. Rather than adopting guidelines from other countries, we argue that regulatory capacity building is more appropriately viewed as a relational concept, referring to the ability to develop regulatory requirements that can cater for different regulatory research needs on an international level and at home

The large grey area between ‘bona fide’ and ‘rogue’ stem cell interventions — ethical acceptability and the need to include local variability

This article aims to put into perspective the binary opposition between ‘scientific’ clinical research trials and ‘rogue’ experimental stem cell therapies, and to show why the ethics criteria used by the dominant science community are not suitable for distinguishing between adequate and inadequate treatments. By focusing on the grey area between clinical stem cell trials and stem cell experimentation, the experimental space where patients, medical professionals and life scientists negotiate for diverging reasons and aims, I show why idealised notions of ethics are not feasible for many stem cell scientists in low- and middle-income countries. Drawing on fieldwork in China from 2012 to 2013, the article asks why ‘the unethical’ according to some is acceptable to Chinese life scientists. The case study of stem cell service provider Beike Biotech illustrates how stem cell interventions take place in a large grey area, where narrow notions of ethics are blurred with and supplanted by broader notions of ethics, co-determined by estimations of socio-economic, political and cultural understandings of risk, opportunity and benefit. I borrow the term ‘bionetworking’, understood as the entrepreneurial aspects of scientific networks that engage in creating biomedical products, to analyse various forms of medical experimentation. I speak of the ‘externalisation’ and ‘internalisation’ of local factors to elucidate how features of patient populations and their environments are subsumed in clinical research applications. Compared to polarised views of stem cell therapy, this approach increases the transparency of clinical interventions and broadens our understanding of why ‘stem cell tourism’ to some is ‘stem cell therapy’ to others

A scaffold-free graft for large critical size bone defect: preclinical evidence to clinical proof of concept

Background & Aim : Large critical-sized bone defect (CBD) remains a challenging pathology in orthopaedics. The direct application of adipose stem cells (ASCs) remains limited by a low homing efficiency and a low survival rate. This study aims to show the osteogenic role of ASCs in a scaffold-free approach. [...

Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases : updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE)

These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune-mediated neurological diseases and provide recommendations for patient selection, transplant technique, follow-up and future development. The major focus is on autologous HSCT (aHSCT), used in MS for over two decades and currently the fastest growing indication for this treatment in Europe, with increasing evidence to support its use in highly active relapsing remitting MS failing to respond to disease modifying therapies. aHSCT may have a potential role in the treatment of the progressive forms of MS with a significant inflammatory component and other immune-mediated neurological diseases, including chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica, myasthenia gravis and stiff person syndrome. Allogeneic HSCT should only be considered where potential risks are justified. Compared with other immunomodulatory treatments, HSCT is associated with greater short-term risks and requires close interspeciality collaboration between transplant physicians and neurologists with a special interest in these neurological conditions before, during and after treatment in accredited HSCT centres. Other experimental cell therapies are developmental for these diseases and patients should only be treated on clinical trials

Single cell transcriptomics reveals heterogeneity and zonation in the adult and infant human liver

Background & Aim: The multiple vital functions of the human liver are tightly linked to its complex organization of highly specialized parenchymal and non-parenchymal cells within the liver lobule. Following the recent advances in next generation sequencing at the resolution of isolated cells, whole liver heterogeneity can currently be studied without the need to sort cells, thereby providing a comprehensive atlas of different hepatic populations, for a better understanding of liver functions and potential implications in liver cell transplantation and regenerative medicine. In this study, we aimed at describing a first high-resolution transcriptomic map of the infant and adult human liver by single-cell transcriptomics. Methods, Results & Conclusion: 80,000 liver cells obtained after collagenase digestion of two human livers(Hepatic Biobank; Cliniques Universitaires Saint-Luc) were loaded in a 10X Genomics instrument to generate 8 independent liver cell libraries. The libraries were sequenced using the Illumina technology in order to reach an average of 65,000 reads/cells. The data generated for both donors were analyzed separately and cell clusters were identified and zonated according to previously established functional, transcriptional and histological studies performed in mice and human. A total of ~28,000 single-cell transcriptomes were obtained from the 8 libraries, of which ~78%, 3% and 18% corresponds to hepatocytes, cholangiocytes and non-parenchymal cells, respectively. Taking specific gene expression patterns related to well-known zonated liver metabolic functions as a reference, the single-cell transcriptomes obtained for hepatocytes have been localized along the portocentral axis, revealing the pericentral-, periportal- and midzonal-specific hepatocyte transcriptomes. Within the clusters of cholangiocytes and non-parenchymal cells, our preliminary results identified multiple subpopulations, including 2 distinct populations of hepatic stellate cells, of which the transcriptomic disparities suggests functional specializations. Thus, our study provides a comprehensive transcriptomic map of the native human liver at a high resolution. It contributes to a better understanding of the heterogeneity and complex organization of the liver cell (sub)populations that underlies the physiology of the human liver, i.e. a prerequisite for the development of next generation applications in liver cell therapy

Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE)

These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune-mediated neurological diseases and provide recommendations for patient selection, transplant technique, follow-up and future development. The major focus is on autologous HSCT (aHSCT), used in MS for over two decades and currently the fastest growing indication for this treatment in Europe, with increasing evidence to support its use in highly active relapsing remitting MS failing to respond to disease modifying therapies. aHSCT may have a potential role in the treatment of the progressive forms of MS with a significant inflammatory component and other immune-mediated neurological diseases, including chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica, myasthenia gravis and stiff person syndrome. Allogeneic HSCT should only be considered where potential risks are justified. Compared with other immunomodulatory treatments, HSCT is associated with greater short-term risks and requires close interspeciality collaboration between transplant physicians and neurologists with a special interest in these neurological conditions before, during and after treatment in accredited HSCT centres. Other experimental cell therapies are developmental for these diseases and patients should only be treated on clinical trials