AUTOSTEM will develop closed, scaleable and automated systems for therapeutic cell manufacture. The project vision is a donor-to-patient system where all aspects of processing, from tissue harvest to patient delivery are fully closed and aseptic. The process will involve new methods of biological cell selection from marrow, fat or other tissues, bioreactors to achieve scale and media formulations that are fully xeno-free. Process monitoring will utilise remote sensing and the automated retrieval of cells for microscopy, flow cytometry, karyotyping, differentiation or other tests. The final product will be a cryobag containing a specified cell dose, ready for thawing and clinical delivery. AUTOSTEM will be the factory of the future for therapeutic cell manufacturing. This system could ultimately be scaled for hospital-based use to produce autologous cells or at industrial scale for allogeneic therapy. It will achieve consistent cell production, minimise contamination, maximise scale and reduce cost of goods, thus enabling routine clinical use of cell therapies. The consortium will be a partnership of academic centres and industry with expertise across the disciplines relevant to the research and development goals. It will also include expertise in GMP and regulatory compliance and in healthcare economic analysis.

Type 2 diabetes will affect >500 million adults by 2040 and its secondary complications will generate enormous socioeconomic costs - in particular, diabetic kidney disease (DKD), which is already the most common cause of chronic kidney disease. DKD is associated with greatly increased mortality and frequently progresses to end stage renal failure. Pharmacotherapy, dialysis and transplantation represent the mainstay treatments for DKD but are costly and provide only limited protection against adverse outcomes. Mesenchymal Stromal Cell (MSC) therapy is a promising approach to halting the progression of DKD toward end-stage renal failure and may also have ancillary benefits in Type 2 diabetes. In preliminary research, we have demonstrated that a single dose of MSC simultaneously improves kidney function (glomerular filtration rate and albuminuria) as well as hyperglycaemia in animals with DKD. NEPHSTROM will conduct a multi-centre, placebo-controlled clinical trial of a novel MSC therapy for stabilization of progressive DKD, leading to superior clinical outcomes and long-term socioeconomic benefit. A key enabler for this trial is a novel MSC population (CD362+MSC, trade name ORBCEL-M) which delivers higher purity and improved characterisation compared to conventional plastic-adherent MSC. The NEPHSTROM Phase 1b/2a clinical trial will investigate the safety, tolerability and preliminary efficacy of a single intravenous infusion of allogeneic ORBCEL-M versus placebo in adults with progressive DKD. NEPHSTROM investigators will also determine the bio-distribution, mechanisms of action, immunological effects and economic impacts associated with ORBCEL-M therapy for DKD. This research will critically inform the optimal design of subsequent Phase 3 trials of ORBCEL-M. Stabilising progressive DKD through NEPHSTROM’s next-generation MSC therapy will reduce the high all-cause mortality and end-stage renal failure risk in people with this chronic non-communicable disease