Prostaglandin E2 Stimulates the Expansion of Regulatory Hematopoietic Stem and Progenitor Cells in Type 1 Diabetes.

Hematopoietic stem and progenitor cells (HSPCs) are multipotent stem cells that have been harnessed as a curative therapy for patients with hematological malignancies. Notably, the discovery that HSPCs are endowed with immunoregulatory properties suggests that HSPC-based therapeutic approaches may be used to treat autoimmune diseases. Indeed, infusion with HSPCs has shown promising results in the treatment of type 1 diabetes (T1D) and remains the only "experimental therapy" that has achieved a satisfactory rate of remission (nearly 60%) in T1D. Patients with newly diagnosed T1D have been successfully reverted to normoglycemia by administration of autologous HSPCs in association with a non-myeloablative immunosuppressive regimen. However, this approach is hampered by a high incidence of adverse effects linked to immunosuppression. Herein, we report that while the use of autologous HSPCs is capable of improving C-peptide production in patients with T1D, ex vivo modulation of HSPCs with prostaglandins (PGs) increases their immunoregulatory properties by upregulating expression of the immune checkpoint-signaling molecule PD-L1. Surprisingly, CXCR4 was upregulated as well, which could enhance HSPC trafficking toward the inflamed pancreatic zone. When tested in murine and human in vitro autoimmune assays, PG-modulated HSPCs were shown to abrogate the autoreactive T cell response. The use of PG-modulated HSPCs may thus provide an attractive and novel treatment of autoimmune diabetes.

Dilemma of renal disease in elderly.

The aging process results in profound anatomic and functional changes in a number of human body systems. Changes in kidney function with normal aging are the most dramatic of any human organ or organ system. These include anatomical, physiological, hemodynamic and immunological changes. Increased propensities of systemic diseases and exposure to poly-pharmacy of the aged group have an additive deleterious effect. The aforementioned changes have its implications on clinical presentations, management and prognosis of all renal diseases in elderly. Atypical presentation, more frequent and longer course are the characteristics of acute renal failure in this age group. Also, presentation of glomerular diseases, clinical course, prognosis, decision of performing a renal biopsy and use of immunosuppressive drugs in elderly specially those subgroup above 80 years of age are still a big challenges that needs a consensus and standardization.