In modern biology, the correct identification of cell types is required for the developmental study of tissues and organs and the production of functional cells for cell therapies and disease ...modeling. For decades, cell types have been defined on the basis of morphological and physiological markers and, more recently, immunological markers and molecular properties. Recent advances in single-cell RNA sequencing have opened new doors for the characterization of cells at the individual and spatiotemporal levels on the basis of their RNA profiles, vastly transforming our understanding of cell types. The objective of this review is to survey the current progress in the field of cell-type identification, starting with the Human Cell Atlas project, which aims to sequence every cell in the human body, to molecular marker databases for individual cell types and other sources that address cell-type identification for regenerative medicine based on cell data guidelines.
The generation of human embryonic stem cell banking networks has ensured that well-characterized and quality controlled stem cell lines are broadly accessible to researchers worldwide. Here, we ...provide recommendations for engaging these established networks in efforts to build similar resources for the distribution and collection of induced pluripotent stem cells.
The development of human pluripotent stem cell (PSC)‐derived medicinal products has been gathering steam in recent years, but the translation of research protocols into GMP production remains a ...daunting task. The challenges not only reside with the nature of cellular therapeutics but are also rooted in the general inexperience in industry‐scale production of stem cell products. Manufacturers of PSC‐derived products should be aware of the technical nuances and take a holistic approach toward early planning and engagement with their academic partners. While not all issues will be readily resolved soon, the collective knowledge and consensus by the manufacturers and key stakeholders will help to guide rapid progression of the field.
This paper highlights and discusses the range and timing of issues that must be considered in the development of cell‐based medicines. Considerable work can be done to assure the robustness of a manufacturing system during early research and development which can then be refined more smoothly during product development. Development of characterisation and safety testing proceeds from a stage and potency assay development may continue into clinical phases.
The International Stem Cell Banking Initiative(ISCBI) was started in 2007 to bring together the leading stem cell banks distributing human pluripotent stem cell (hPSC) lines for research and ...development, to discuss best practice across a range of issues from donor consent to delivery of cells for use in research, diagnostics and cell-based medicines. ISCBI holds workshops around the world and on-line and regularly publishes summaries of discussions and consensus amongst experts in stem cell biology, biobanking technology, regulation and policy making. To date, experts from more than 28 countries have contributed to ISCBI activities which are frequently run in collaboration with other stem cell organisations and has co-ordinated closely with the International Stem Cell Initiative and the hPSCreg European Commission funded database of hPSC lines and clincal trials.
•EBiSC is a non-profit centralised bank which collects, stores and distributes human iPSC lines generated by different research groups internationally.•EBiSC has developed a robust and flexible ...quality control screening regime suitable for screening high numbers of lines.•Strict release criteria ensure safety and integrity of distributed iPSC lines.•Informational testing provides full characterisation and assessment of performance in culture.•Data is made available to users via the EBiSC catalogue to inform iPSC line selection prior to purchase.•Managed access genomic datasets are available through the EBiSC data access committee.
The European Bank for induced Pluripotent Stem Cells (EBiSC) has collected iPSC lines associated with genetic diseases and healthy controls from across Europe and made these available for research use to international academic and commercial users. Ensuring availability of consistently high quality iPSCs at scale and from various sources requires quality systems which are flexible yet robust, maximising the utilisation of available resources. Here, we outline the establishment and implementation of a quality control regime suitable for a large-scale operational setting. Strict release testing ensures the safety and integrity of distributed iPSC lines, whilst informational testing allows publication of full characterisation and assessment of iPSC lines. Quality control screening is underpinned by a ‘fit-for-purpose’ Quality Management System giving full traceability and supporting continuous scientific and process development. Evaluation and qualification of key assays and techniques ensures that assay sensitivities and limits of detection are acceptable. Use of rapid testing techniques in place of more ‘traditional’ assays allows EBiSC to respond quickly to user demand, generating fully qualified iPSC line banks in a labour-saving and cost-efficient manner.
Pluripotent stem cells may acquire genetic and epigenetic variants during culture following their derivation. At a conference organized by the International Stem Cell Initiative, and held at The ...Jackson Laboratory, Bar Harbor, Maine, October 2016, participants discussed how the appearance of such variants can be monitored and minimized and, crucially, how their significance for the safety of therapeutic applications of these cells can be assessed. A strong recommendation from the meeting was that an international advisory group should be set up to review the genetic and epigenetic changes observed in human pluripotent stem cell lines and establish a framework for evaluating the risks that they may pose for clinical use.
The International Stem Cell Initiative organized a conference to review current understanding of the detection, origins, and consequences of genetic and epigenetic variants that arise in cultures of human pluripotent stem cells. This report provides an overview of the discussions and a recommendation to form an advisory group to help reach an international consensus on risk assessment for clinical applications.
Human pluripotent stem cells (hPSC) have the capability to deliver novel cell‐based medicines that could transform medical treatments for a wide range of diseases including age‐related degenerative ...disorders and traumatic injury. In spite of significant investment in this area, due to the novel nature of these hPSC‐based medicines, there are challenges in almost all aspects of their manufacturing including bioprocessing, characterization and delivery. The Chinese Academy of Sciences and the Chinese Society for Stem Cell Research have collaborated to create a new discussion forum called PSConf 2021 (Pluripotent Stem Cell Conference 2021), intended to promote exchanges in communication on cutting‐edge developments and international coordination in hPSC manufacturing. The PSConf 2021 addressed crucial topics in stem cell‐based manufacturing, including stem cell differentiation, culture scale‐up, product formulation and release. This report summarizes the proceedings and conclusions from the discussion sessions, and it is accompanied by publication of individual papers from the speakers at the PSConf 2021.
Significance Statement
The PSConf 2021 meeting has brought together speakers and delegates from more than 20 countries in an informal discussion forum focusing on the manufacture of cell‐based medicines using hPSCs. The conference discussion sessions enabled an open exchange of information on the latest developments, ideas on key challenges and their potential solutions. It also captured the experiences and lessons learnt by professionals who had been in the field from the earliest applications of human embryonic stem cells, and presented a diverse range of new potential pluripotent stem cell‐based medicines that are now under development, with some already in clinical trials.
Challenges in the manufacture of human plurtipotent stem cell‐based medicines.
Brain degeneration and damage is difficult to cure due to the limited endogenous repair capability of the central nervous system. Furthermore, drug development for treatment of diseases of the ...central nervous system remains a major challenge. However, it now appears that using human pluripotent stem cell‐derived neural cells to replace degenerating cells provides a promising cell‐based medicine for rejuvenation of brain function. Accordingly, a large number of studies have carried out preclinical assessments, which have involved different neural cell types in several neurological diseases. Recent advances in animal models identify the transplantation of neural derivatives from pluripotent stem cells as a promising path toward the clinical application of cell therapies Stem Cells Transl Med 2019;8:681‐693; Drug Discov Today 2019;24:992‐999; Nat Med 2019;25:1045‐1053. Some groups are moving toward clinical testing in humans. However, the difficulty in selection of valuable critical quality criteria for cell products and the lack of functional assays that could indicate suitability for clinical effect continue to hinder neural cell‐based medicine development Biologicals 2019;59:68‐71. In this review, we summarize the current status of preclinical studies progress in this area and outline the biological characteristics of neural cells that have been used in new developing clinical studies. We also discuss the requirements for translation of stem cell‐derived neural cells in examples of stem cell‐based clinical therapy.
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