50 million diabetic EU citizens are using approved anti-diabetic agents to control their glycaemia. However, suboptimal glycemic control leads to 6 progressive diabetic complications, namely: nephropathy, retinopathy, cardiomyopathy, neuropathy and foot ulceration. In 2010, 11% of EU adult deaths (634,000) were caused by diabetic complications. These distinct disorders have few effective medicines and present challenging management issues for clinicians. Stromal Stem Cells (SSC) are a mixed population of plastic-adherent (PA) cells isolated from adult bone marrow. PA-SSC secrete potent immunosuppressive and angiogenic proteins and over 100 clinical trials are testing PA-SSC in 40 distinct autoimmune and ischemic diseases. Notably, preclinical studies show a single intravenous administration of un-modified PA-SSC can control rodent hyperglycaemia, prompting 10 recent clinical safety studies in diabetic patients. REDDSTAR will comprehensively examine if SSC can safely repair all 6 damaged tissues and control glycaemia in three different species. To facilitate this we identified an antibody (S2) that prospectively isolates comparable, equivalent S2+SSC from human, rat, mouse and rabbit marrow, enabling testing of pure S2+/- SSC and mixed PA-SSC from each species for the first time. Furthermore, separation of PA-SSC into S2+ and S2- fractions reveal functionally distinct populations. REDDSTAR partners have collectively developed five distinct clinically-relevant in vivo models of the 6 key diabetic complications. We will assess if S2+, S2- and PA-SSC exert differing control of glycaemia and tissue repair in each model. Finally, REDDSTAR partners are developing the first benchtop GMP-grade nanosorter, enabling clinical purification of S2+ and S2- SSC for human safety trials. We will dissect how S2+ and S2- SSC simultaneously repair tissue damage and maintain glycaemic control, an effect not observed with any current therapy.