Pancreas-derived mesenchymal stromal cells share immune response-modulating and angiogenic potential with bone marrow mesenchymal stromal cells and can be grown to therapeutic scale under Good Manufacturing Practice conditions.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) isolated from various tissues are under investigation as cellular therapeutics in a wide range of diseases. It is appreciated that the basic biological functions of MSCs vary depending on tissue source. However, in-depth comparative analyses between MSCs isolated from different tissue sources under Good Manufacturing Practice (GMP) conditions are lacking. Human clinical-grade low-purity islet (LPI) fractions are generated as a byproduct of islet isolation for transplantation. MSC isolates were derived from LPI fractions with the aim of performing a systematic, standardized comparative analysis of these cells with clinically relevant bone marrow-derived MSCs (BM MSCs). METHODS: MSC isolates were derived from LPI fractions and expanded in platelet lysate-supplemented medium or in commercially available xenogeneic-free medium. Doubling rate, phenotype, differentiation potential, gene expression, protein production and immunomodulatory capacity of LPIs were compared with those of BM MSCs. RESULTS: MSCs can be readily derived in vitro from non-transplanted fractions resulting from islet cell processing (i.e., LPI MSCs). LPI MSCs grow stably in serum-free or platelet lysate-supplemented media and demonstrate in vitro self-renewal, as measured by colony-forming unit assay. LPI MSCs express patterns of chemokines and pro-regenerative factors similar to those of BM MSCs and, importantly, are equally able to attract immune cells in vitro and in vivo and suppress T-cell proliferation in vitro. Additionally, LPI MSCs can be expanded to therapeutically relevant doses at low passage under GMP conditions. CONCLUSIONS: LPI MSCs represent an alternative source of GMP MSCs with functions comparable to BM MSCs.

Human umbilical cord perivascular cells improve human pancreatic islet transplant function by increasing vascularization.

Islet transplantation is an efficacious therapy for type 1 diabetes; however, islets from multiple donor pancreata are required, and a gradual attrition in transplant function is seen. Here, we manufactured human umbilical cord perivascular mesenchymal stromal cells (HUCPVCs) to Good Manufacturing Practice (GMP) standards. HUCPVCs showed a stable phenotype while undergoing rapid ex vivo expansion at passage 2 (p2) to passage 4 (p4) and produced proregenerative factors, strongly suppressing T cell responses in the resting state and in response to inflammation. Transplanting an islet equivalent (IEQ):HUCPVC ratio of 1:30 under the kidney capsule in diabetic NSG mice demonstrated the fastest return to normoglycemia by 3 days after transplant: Superior glycemic control was seen at both early (2.7 weeks) and later stages (7, 12, and 16 weeks) versus ratios of 1:0, 1:10, and 1:50, respectively. Syngeneic islet transplantation in immunocompetent mice using the clinically relevant hepatic portal route with a marginal islet mass showed that mice transplanted with an IEQ:HUCPVC ratio of 1:150 had superior glycemic control versus ratios of 1:0, 1:90, and 1:210 up to 6 weeks after transplant. Immunodeficient mice transplanted with human islets (IEQ:HUCPVC ratio of 1:150) exhibited better glycemic control for 7 weeks after transplant versus islet transplant alone, and islets transplanted via the hepatic portal vein in an allogeneic mouse model using a curative islet mass demonstrated delayed rejection of islets when cotransplanted with HUCPVCs (IEQ:HUCPVC ratio of 1:150). The immunosuppressive and proregenerative properties of HUCPVCs demonstrated long-term positive effects on graft function in vivo, indicating that they may improve long-term human islet allotransplantation outcomes.

Scotblood 2015: Improving and delivering blood products, novel cellular therapies, and celebrating patients and donor engagement within transfusion services.

Blood Transfusion Services are striving to continually improve the efficacy and quality of their blood products whilst also simultaneously diversifying into novel cellular products. For this to be successful the relationships between the various arms of the organisation must be strong and interlinked. As new technologies impact on the products that blood transfusion services supply it should be noted that the interaction between the service and its donor base is also affected by advancing technologies. Social media has fundamentally altered the way in which the public can access information and news, as such blood services must engage and interact appropriately with these new forms of media. As a reflection of these challenges the Scotblood 2015 programme was focussed on service and product improvement, donor engagement and people centred transfusion. This commentary comprises summaries of the presentations, based in part on the abstracts provided by the speakers.

Mesenchymal stromal cells as multifunctional cellular therapeutics - a potential role for extracellular vesicles.

Mesenchymal stromal cells (MSCs), multipotent cells present in tissues throughout the body, can reconstitute adipogenic, osteogenic and chondrogenic tissues, but are also of great interest as mediators of immune modulation and suppression. MSCs are able to improve transplant engraftment, treat graft versus host disease and suppress T cell responses and therefore have great potential as therapeutic agents. Their immune modulatory capacity is mediated through both cell-to-cell contact and cytokine secretion, but it is becoming clear that extracellular vesicles (EV) produced by MSC also possess immunomodulatory properties. These vesicles are easy to prepare and store, do not carry nuclear material and cannot form tumours, and therefore also represent a highly desirable therapeutic agent. This review outlines the formation and characterisation of extracellular vesicles, the reported function of MSC-EVs in vitro and in vivo, and addresses some of the emerging issues with nomenclature, EV therapeutic dose and tissue source. The development of GMP-grade production protocols and effective characterisation of MSC extracellular vesicles is essential to their successful use as immune modulating therapeutic agents, and this review outlines the current status of the research in this area.

Innovative research, improving quality, and celebrating patient successes and the role of donors within transfusion services.

A modern successful Blood service is reliant on numerous elements to continually improve. With the constant increments in regulatory and quality management legislation the backbone to the service requires the implementation and maintenance of a modern Quality management system. It also relies on successful relationships between the various arms of the organisation in driving the service forward, and finally it is dependent on a relationship between its donor base and the staff. It is vital that those involved with transfusion appreciate the impact that they are having on the donors and patients, and it is important to appreciate and engage with donors without whom there would be no transfusion or transplantation. As a reflection of this the Scotblood 2014 programme was focused on service improvement and people centred transfusion. This commentary comprises summaries of the presentations, based in part on the abstracts provided by the speakers.

Optimal use of blood and innovative approaches to stem cells, regenerative medicine and donor recruitment.

The annual scientific meeting of the Scotblood National Blood Transfusion Service, (SNBTS), continues to enjoy success. Scotblood 2013 focused on the contemporary issues affecting the various essential areas of blood transfusion and transfusion medicine. Presentations ranged from the challenges of recruiting young donors, forecasting future blood demand and celebrating the success of the better blood transfusion program. The meeting also discussed potential future developments in regenerative medicine particularly the potential of mesenchymal stromal cells and discussion of the ongoing Bloodpharma project, the ultimate aim of developing cultured red blood cells. This commentary comprises summaries of the presentations, based in part on the abstracts provided by the speakers. The Scotblood Conference began with the welcoming introduction by SNBTS Director Mrs. Mary Morgan, during which she updated the ongoing developments within SNBTS over the last year. Mrs. Morgan described how SNBTS met the challenges and obstacles that have been prevalent in all Blood Transfusion Services, whilst also meeting the transfusion needs of the people of Scotland. Mrs. Morgan then introduced the keynote speaker Dr. Aileen Keel CBE, Deputy Chief Medical Officer of Scotland. Dr. Keel's presentation was entitled "Twenty years in the Scottish Government-edited highlights" in which she described the various challenges that have presented themselves to her throughout her career. Dr. Keel highlighted how the various risks in the blood transfusion field (from HCV, HIV through to nvCJD) have arisen and then reduced to miniscule levels through hard work and perseverance. The highlights of the conference are summarised below.

Scotblood 2012: transfusion/transplant medicine in the 2nd decade of the 21st century.

Transfusion medicine is a technology-based discipline, undergoing continual changes for improvement. It requires staff at all levels to be continually educated and trained in appropriate multidisciplinary skills, in line with the rapid developments in all areas of transfusion practice: from blood/organ collection, through processing and storage to the more advanced cellular and hospital-based transfusion/transplantation therapies. Whilst the majority of the challenges to improve hospital and general transfusion practice can be overcome through team work, education, timely objectives and perseverance, it is important to envisage opportunities for implementing digital technologies to reduce all of the applicable hazards associated with transfusion. These can vary widely from new and emerging pathogens to limitations of supply due to growing demographic changes in populations. In the first decade of 21st century we have already witnessed unprecedented advances in haematopoietic stem cell transplantation to minimise the toxicities of graft versus host disease (GvHD), and in cell therapy to explore immunotherapy against cancer and other malignant disorders. Today there are 1000 genome project hapmaps that only the extreme cost of their implementation to routine practices may limit. Transfusion medicine, like all disciplines of medicine, nevertheless, will face difficult choices between increasing healthcare technology and increasing worldwide health. Drs. Colligan and McGowan, the new lead organisers of this wonderful yearly educational programme have agreed to follow the previous organisers' strategy to make a summary report of their meeting to become available, through TRASCI to broader interested groups, with the sprit that "sharing is caring". The main highlights of the 2012 conference were: targeting transfusion practices in hospital, a continuing journey; emerging infections and the potential causes and possible remedial actions; building for the future; the challenging issues of donor recruitment/retention; and finally; the application of Information Technology as a decision making tool, utilising clinical audit monitoring to evaluate good practice. This year's conference also coincided with the retirement of Martin Bruce OBE, after his 41years distinguished career, who gave the most delightful and humorous talk of a" life time of learning" which delighted all the participants. Finally, 2012 also marked the retirements of the previous lead Scotblood organisers Prof. Robin Fraser and Dr. Hagop Bessos after over thirty years service to SNBTS, and to whom we would like to dedicate this meeting report and wish them a happy and healthy retirement. This commentary comprises summaries of the presentations, based in part on the abstracts provided by the speakers.