We tested the hypothesis that multipotent stromal cells from human bone marrow (hMSCs) can provide a potential therapy for human diabetes mellitus. Severe but nonlethal hyperglycemia was produced in NOD/ scid mice with daily low doses of streptozotocin on days 1–4, and hMSCs were delivered via intracardiac infusion on days 10 and 17. The hMSCs lowered blood glucose levels in the diabetic mice on day 32 relative to untreated controls (18.34 mM ± 1.12 SE vs. 27.78 mM ± 2.45 SE, P = 0.0019). ELISAs demonstrated that blood levels of mouse insulin were higher in the hMSC-treated as compared with untreated diabetic mice, but human insulin was not detected. PCR assays detected human Alu sequences in DNA in pancreas and kidney on day 17 or 32 but not in other tissues, except heart, into which the cells were infused. In the hMSC-treated diabetic mice, there was an increase in pancreatic islets and β cells producing mouse insulin. Rare islets contained human cells that colabeled for human insulin or PDX-1. Most of the β cells in the islets were mouse cells that expressed mouse insulin. In kidneys of hMSC-treated diabetic mice, human cells were found in the glomeruli. There was a decrease in mesangial thickening and a decrease in macrophage infiltration. A few of the human cells appeared to differentiate into glomerular endothelial cells. Therefore, the results raised the possibility that hMSCs may be useful in enhancing insulin secretion and perhaps improving the renal lesions that develop in patients with diabetes mellitus.

We screened for surface proteins expressed only by the early progenitor cells present in low-passage, low-density cultures of the adult stem/progenitor cells from bone marrow referred to as mesenchymal stem cells or multipotent stromal cells (MSCs). Six proteins were identified that were selectively expressed in the early progenitors: podocalyxin-like protein (PODXL), α6-integrin (CD49f), α4-integrin (CD49d), c-Met, CXCR4, and CX3CR1. All were previously shown to be involved in cell trafficking or tumor progression. Antibodies to CD49f and PODXL, a sialomucin in the CD34 family, were the most robust for FACScan assays. PODXL^hi/CD49f^hi MSCs were more clonogenic and differentiated more efficiently than PODXL^lo/CD49f^lo cells. Inhibition of expression of PODXL with RNA interference caused aggregation of the cells. Furthermore, PODXL^hi/CD49f^hi MSCs were less prone to produce lethal pulmonary emboli, and larger numbers were recovered in heart and kidney after intravenous infusion into mice with myocardial infarcts.

The Fourth Expert Meeting of the Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Consortium took place in Barcelona on October 19 and 20, 2012. This meeting focused on the translation of preclinical data into early clinical settings. This position paper highlights the main topics explored on the safety and efficacy of mesenchymal stem cells as a therapeutic agent in solid organ transplantation and emphasizes the issues (proper timing, concomitant immunossupression, source and immunogenicity of mesenchymal stem cells, and oncogenicity) that have been addressed and will be followed up by the MiSOT Consortium in future studies.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Andreyan N. Osipov1, 2, 3, 4, Margarita Pustovalova1, 2, Anna Grekhova1, 5, Petr Eremin1, Natalia Vorobyova1, 3, Andrey Pulin1, Alex Zhavoronkov4, 6, 7, Sergey Roumiantsev3, 4, 8, Dmitry Y. Klokov9, Ilya Eremin1 1State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow, Russia 2Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia 3Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia 4Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia 5Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, Moscow, Russia 6Insilico Medicine, Inc, ETC, Johns Hopkins University, Baltimore, Maryland, USA 7The Biogerontology Research Foundation, BGRF, London, UK 8N.I. Pirogov Russian National Research Medical University, Moscow, Russia 9Canadian Nuclear Laboratories, Chalk River, Ontario, Canada Correspondence to: Andreyan N. Osipov, e-mail: andreyan.osipov@gmail.com Keywords: mesenchymal stem cells, DNA double-strand breaks, DNA repair, X-rays, low doses Received: April 08, 2015 Accepted: July 10, 2015 Published: July 23, 2015

H2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation γH2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation