Generation of clinical grade human pluripotent stem cells (iPSCs) using safe mRNA reprogramming strategy

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"Since their discovery in 2006, induced pluripotent stem cells (iPSC) have demonstrated their importance to disease modelling, drug discovery and regenerative medicine. Using genes/transcription factors associated with embryonic maintenance, 'adult' somatic cells are reprogrammed or induced to an embryonic-like state. This creates cells with the properties of self-renewal and pluripotent potential (meaning they can be used to create any cell type) whilst alleviating the ethical constraints often associated with embryonic derived material. In addition, iPSCs cells may be used for autologous therapies (using the patient's own cells) or, with careful selection of the donor, allow HLA matched, O negative cell banks for multiple recipients (allogeneic therapies which use cells from different donors that are compatible with the immune system of the patient receiving the stem cell therapy).To date, most research in iPSCs has been conducted at an early pre-clinical stage; a major challenge is to make the protocols for generating iPSCs suitable for clinical use. Many of the existing protocols require an enormous amount of quality testing because the viruses/genes/transcription factors may integrate into the genome, causing undesirable changes and increasing the risk of tumours if they are not cleared from the cells. mRNA reprogramming avoids these safety concerns as mRNA does not integrate into the genome and remains within the cell for only a short period. However, suitable clinical-grade protocols have not yet been fully developed for the manufacturing processes.This project proposes a novel strategy for the derivation of clinical iPSCs which have the properties associated with human embryonic stem cells whilst being derived from minimal blood from adults. By using a non-integrating mRNA reprogramming method, the risk of tumour formation usually associated with other methods is avoided.To make the process economically attractive, manufacturing procedures will be standardised to allow an automated work flow from donor material, reprogramming, iPSC generation and cell-banking. This will allow quicker and safer generation of clinical grade iPSCs for both allogeneic and autologous therapies and provide scope for commercialisation and licensing of the generated cell lines to the biotechnology sector.Bringing together the expertise of RoslinCT and REPROCELL will provide a step change in the production of clinical grade iPSCs and centre this know-how and manufacturing within the UK."