Stem cell therapy for microvascular injury associated with ischemic nephropathy

Ischemic nephropathy reflects progressive loss of kidney function due to large vessel atherosclerotic occlusive disease. Recent studies indicate that this process is characterized by mi-crovascular rarefaction, increased tissue hypoxia and activation of inflammatory processes of tissue injury. This review summarizes the rationale and application of functional MR imaging to evaluate tissue oxygenation in human subjects that defines the limits of renal adaptation to reduction in blood flow, development of increasingly severe tissue hypoxia and recruitment of inflammatory injury pathways in ischemic nephropathy. Human mesenchymal stromal/stem cells (MSC) are capable of modifying angiogenic pathways and immune responses, but the potency of these effects vary between individuals and various clinical characteristics including age and chronic kidney disease and levels of hypoxia. We summarize recently completed first-in-human studies applying intrarenal infusion of autologous adipose-derived MSC in human subjects with ischemic nephropathy that demonstrate a rise in blood flow and reduction in tissue hypoxia consistent with partial repair of microvascular injury, even without restoring main renal arterial blood flow. Inflammatory biomarkers in the renal vein of post-stenotic kidneys fell after MSC infusion. These changes were associated with modest but significant dose-related increments in kidney function. These data provide support a role for autologous MSC in repair of microvascular injury associated with tissue hypoxia.