Chris Mason

A brief definition of regenerative medicine.

While it could be said that regenerative medicine is what this journal publishes, that would be cyclical. It could also be claimed that most people interested in the field have a good grasp of what is entailed, and this is probably correct. But, as the field grows and there is a need to carry governments and public opinion along, it is probably worth having a simple explanation of regenerative medicine. And, it is simplicity that is the nub of the matter. There are already a lot of definitions [1–3] but all are lengthy and not the sort of thing scientists, start-ups or advocates can say succinctly when a pharma executive, government minister or member of the public asks for clarification. Here, we address this and the origins and relationships that help to define the field. One of the complications is that regenerative medicine has grown out of a good deal of prior activity. This includes surgery, surgical implants, such as artificial hips, and increasingly sophisticated biomaterial scaffolds. It also draws on hospital procedures such as bone marrow and organ transplants and it relates to tissue engineering. There is no absolute cut-off in the transformation of these into fully developed regenerative medicine but they each leave residues of their input that can mean the patient is not capable of being termed ‘of natural health’ with respect to the treated condition. Organ transplants often demand immune-suppressing drugs and metal hips can become loose with time, engineered tissue scaffolds can provoke inflammation and bone marrow sources are variable mixtures that also can be contaminated quite easily by the nature of the cell aspiration procedure. The central focus of regenerative medicine is human cells. These may be somatic, adult stem or embryo-derived cells and now there are versions

The potential of optical coherence tomography in the engineering of living tissue

The better repair of human tissue is an urgent medical goal and in order to achieve a safe outcome there is a parallel need for sensitive, non-invasive methods of assessing the quality of the engineered tissues and organs prior to surgical implantation. Optical coherence tomography (OCT) can potentially fulfil this role. The current status of OCT as an advanced imaging tool in clinical medicine, developmental biology and material science is reviewed and the parallels to the engineering of living tissue and organs are discussed. Preliminary data are also presented for a tissue engineering bioreactor with in situ OCT imaging. The data suggest that OCT can be utilized as a real time, non-destructive, non-invasive tool to critically monitor the morphology of tissue-engineered constructs during their fabrication and growth.

Regenerative medicine 2.0

This editorial started life as an ‘end of year report’ style review of the stem cell and regenerative medicine sector. However, during its preparation it became very apparent that 2006 was not just a further 365 days in the gradual continuum from its origins in the laboratories at the Massachusetts Institute of Technology in the 1980s through to a mature industrial sector. 2006 was the year that regenerative medicine started to enter the next phase in its development into a successful and sustainable global healthcare industry. This editorial proposes that the regenerative medicine sector is not moving continuously in one direction from the tissue engineering pioneers through to the establishment of a new commercial sector, but that it is undergoing a similar disjointed journey to that of the World Wide Web. Does this quote from Tim O’Reilly, a leading web commentator and IT book publisher [101], sound familiar?

International community consensus standard for reporting derivation of human embryonic stem cell lines

The development and implementation of new methods in human embryonic stem cell (hESC) research is fraught with difficulties, not least of which is the highly variable reporting of the number and quality of embryos used to derive hESC lines. Without a clear minimum information convention among the derivation teams, understanding and comparing derivation methods and their potential impact on the resulting stem cell line will continue to be extremely difficult. In order to address this issue, we consulted international teams regarding the implementation of a minimum information convention for derivation with the aim of universal use, data collection and central analysis, followed by a multi-author publication. The responses demonstrated overwhelming support for such a system; over 90% of the respondents agreed that a universal standard for reporting the derivation of hESC lines was essential as part of the international effort to advance the field efficiently, and over 87% plan to use this standard and share collected data in Spring 2008 for central analysis and public dissemination. A number of future steps are planned in order to ensure that this standard evolves with the field and remains relevant and up-to-date. Our aim is to incorporate these data within existing international initiatives aimed at improving derivation standards. This article is an open-access publication in order to make the convention freely available to the international community and encourage universal participation.

Cell therapy medical tourism: time for action.

1 Department of Research and Development, Hospira Inc., Lake Forest, Illinois, USA, 2 Department of Medical Ethics, University of Pennsylvania, Philadelphia, Pennsylvania, USA, 3 Advanced Centre for Biochemical Engineering, University College London, London, UK, 4 The Stop ALD Foundation, Houston, Texas, USA, 5 Interdisciplinary Oncology Program, H. Lee Moffi tt Cancer Center & Research Institute, Tampa, Florida, USA, 6 Department of Regulatory Affairs, Perkin Elmer Inc., Cambridge, Massachusetts, USA, 7 Bone Marrow Transplantation Unit, National Cancer Institute, Rio de Janeiro, Brazil, 8 Section of Hematology and Bone Marrow Transplantation Unit, University Hospital, Cremona, Italy, 9 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA, 10 Department of Cell and Molecular Therapies, Royal Prince Alfred Hospital RPA Hospital and Centenary Institute, Newtown, NSW, Australia, 11 Research Foundation for Community Medicine, Tokyo, Japan, and 12 Children ’ s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

Regenerative medicine bioprocessing: the need to learn from the experience of other fields

10.2217/17460751.1.5.615

Proposal for a universal minimum information convention for the reporting on the derivation of human embryonic stem cell lines

The implementation of novel methodologyacross the human embryonic stem cell (hESC)field is fraught with difficulties, not least ofwhich is the highly variable reporting of thenumber and quality of embryos used to deriveeach new hESC line. It is almost impossible toascertain from the literatu re a true efficiency forderiving a hESC line. Until there is a clear min-imum information (MI) convention amongstthe derivation teams, understanding and com-paring novel derivation methodologies andtheir potential impact on the resulting stem cellline will continue to be impossible or at bestextremely difficult. In this editorial, we high-light the variation in data published and voicesuggestions as to how the reporting can becomestandardized and so facilitate progress inhuman embryonic stem cell derivation. Theauthors request that interested parties commenton the system proposed, in order that a consen-sus article can be published in approximately4 months time.There is no universally agreed method forreporting the quality and type of embryo usedas starting material for hESC line derivation.Whilst many groups have published their hESCderivation data and protocols, few have statedin their manuscripts the complete essentialunderlying metadata with respect to theirsource material to enable reliable comparisonsto be made. However, it is beginning to beacknowledged that this lack of an accepted andestablished reporting system results in severalhurdles for stem cell researchers. In clinical-assisted reproduction, standards for embryo andblastocyst quality have been devised that corre-late with likelihood of implantation, and mightbeneficially be applied to stem cell derivation.Many advanced fields of biology have bene-fited greatly from the creation of their ownbespoke reporting standards. These evolvingstandards have enabled all the researchers in aparticular field to make the most of oneanother’s data. Successful examples include theStandard Metabolic Reporting StructuresWorking Group

Preimplantation genetic diagnosis as a source of human embryonic stem cells for disease research and drug discovery

Embryos surplus to therapeutic requirements following preimplantation genetic diagnosis can be used to derive human embryonic stem cell (hESC) lines carrying mutations significant to human disease. These cells provide a powerful in vitro tool for modelling disease progression in a number of cell types as well as having the potential to revolutionise drug discovery. Robust and reproducible directed differentiation protocols are needed to maximise the potential of these cells. In this review, we explore the current use of hESC and induced pluripotent stem cells in disease‐specific research and discuss the use of stem cell technology in drug discovery and toxicity testing.

Regenerative medicine bioprocessing: concentration and behavior of adherent cell suspensions and pastes.

Regenerative medicines based on human cells demand their harvesting, culture, and processing. Manufacturing processes are likely to include cell concentration and subsequent controlled dosing of concentrates, for example, to the patient or tissue construct. The integrity and functionality of the cells must be maintained during these processing stages. In this study the performance of two different cell concentration protocols (involving centrifugation and resuspension) are compared and consideration given to possible causes of cell loss. Further studies examine cell size and rheological behavior of anchorage‐dependent mammalian cell suspensions, and the effect of capillary flow stress (0.5–15u2009Pa, laminar flow regime) on cell number and membrane integrity as quantified by flow cytometry. The cell concentration protocols achieved maximum cell volume fraction of around 0.3 and the improved protocol exhibited intact cell yield of 80u2009±u200913%, demonstrating proof‐of principle for achieving tissue‐like cell concentrations by a process of centrifugation and orbital shaking. Volume mean cell diameter (cell diameter at the mean cell volume) for the rat aortic smooth muscle cells (CRL‐1444) used in this study was 22.4u2009µm. Concentrated cell suspension rheology approximated to power law behavior and exhibited similar trends to reports for plant and yeast cells. Capillary transfer at 2–15u2009Pa (wall shear stress) did not significantly affect cell number or membrane integrity while losses observed at low shear (0.5, 1.0u2009Pa) were probably due to surface attachment of cells in the apparatus. Biotechnol. Bioeng. 2009;103: 1236–1247.

The need for a regen industry voice

The regen industry which develops, manufactures and sells regenerative medicine products is moving forward. Like biotech before it, the challenges to pioneering companies are large but the vision of a medicine that can regenerate is gaining momentum. In this exciting situation the nascent industry needs a way to articulate its vision and to marshal its arguments. It needs a voice. When the biotechnology sector began, startup companies found it very hard to get their arguments heard. Most people in the classical pharmaceutical industry were dismissive of the possibility that protein-based medicines that had to be injected could represent a business. To the chemists who dominated the pharma sector the biology entailed was also alien. The dominant positions in industry associations were all held by such people so that the new breed of biopharmaceutical entrepreneurs had no real forum and over time, and quite painfully in the early days, they built their own. Now, in the USA, the Biotechnology Industry Organization (BIO) [101] is powerful and well organized and there are parallel organizations in Europe linked by the European Association for Bioindustries (EuropaBio) [102]. These organizations have not treated the beginnings of regenerative medicine with disdain, quite the reverse, and their activities contain elements related to stem cells and tissue engineering, albeit small parts of the whole. Although we are not principally concerned here with scientific organizations, it is noticeable also that more established societies are all moving to embrace regenerative medicine. Therefore, researchers do not have a problem in being heard, although here too it is quite often diluted.