Mobilized human hematopoietic stem/progenitor cells promote kidney repair after ischemia/reperfusion injury.

BACKGROUND: Understanding the mechanisms of repair and regeneration of the kidney after injury is of great interest because there are currently no therapies that promote repair, and kidneys frequently do not repair adequately. We studied the capacity of human CD34(+) hematopoietic stem/progenitor cells (HSPCs) to promote kidney repair and regeneration using an established ischemia/reperfusion injury model in mice, with particular focus on the microvasculature. METHODS AND RESULTS: Human HSPCs administered systemically 24 hours after kidney injury were selectively recruited to injured kidneys of immunodeficient mice (Jackson Labs, Bar Harbor, Me) and localized prominently in and around vasculature. This recruitment was associated with enhanced repair of the kidney microvasculature, tubule epithelial cells, enhanced functional recovery, and increased survival. HSPCs recruited to kidney expressed markers consistent with circulating endothelial progenitors and synthesized high levels of proangiogenic cytokines, which promoted proliferation of both endothelial and epithelial cells. Although purified HSPCs acquired endothelial progenitor markers once recruited to the kidney, engraftment of human endothelial cells in the mouse capillary walls was an extremely rare event, indicating that human stem cell mediated renal repair is by paracrine mechanisms rather than replacement of vasculature. CONCLUSIONS: These studies advance human HSPCs as a promising therapeutic strategy for promoting renal repair after injury.

Cardiovascular disease: potential impact of stem cell therapy.

Atherosclerotic vascular disease becomes a clinical problem when there is sufficient atherosclerotic plaque burden and/or endothelial dysfunction to cause a limitation of nutrient blood flow to tissues. However, once myocardial infarction has occurred, there is little, if any, way to stimulate the growth of new blood vessels or cardiac muscle to replace that which has been lost. The potential use of hematopoietic stem cells (HSCs) to treat cardiovascular disease has recently been suggested from preclinical and clinical studies. HSCs are precursors of all the blood cells, but they may also give rise to cells of the vascular system, endothelial cells in the form of endothelial progenitor cells (EPCs). Clinical trials have been conducted in patients with either acute myocardial infarction or limb ischemia to determine the initial effectiveness and safety of this treatment approach. These studies demonstrated the potential clinical effectiveness of this stem cell approach to the treatment of patients with acute myocardial ischemia and limb ischemia. Today, more preclinical studies are planned to elucidate the mechanism by which transplanted stem cells can home and differentiate into these endothelial cells and cardiac muscle cells. At the same time, new clinical trials are planned to evaluate both chronic, stable as well as acute myocardial ischemia and limb ischemia with CD34+ and CD133+ stem cells, as well as with further selected EPCs and mesenchymal stem cells.

Evaluation of NuStatr, a Novel Nonimpregnated Hemostatic Dressing, Compared With Combat Gauze in Severe Traumatic Porcine Hemorrhage Model.

BACKGROUND: Uncontrolled hemorrhage remains one of the most challenging problems facing emergency medical professionals and a leading cause of traumatic death in both battlefield and civilian environments. Survival is determined by the ability to rapidly control hemorrhage. Several commercially available topical adjunct agents have been shown to be effective in controlling hemorrhage, and one, Combat Gauze (CG), is used regularly on the battlefield and for civilian applications. However, recent literature reviews have concluded that no ideal topical agent exists for all injuries and scenarios. The authors compared a novel nonimpregnated dressing composed of cellulose and silica, NuStat (NS), to CG in a lethal hemorrhagic groin injury. These dressings were selected for their commercial availability and design intended for control of massive hemorrhage. METHODS: A complex penetrating femoral artery groin injury was made using a 5.5mm vascular punch followed by 45 seconds of uncontrolled hemorrhage in 15 swine. The hemostatic dressings were randomized using a random sequence generator and then assigned to the animals. Three minutes of manual pressure was applied with each agent after the free bleed. Hextend bolus (500 mL) was subsequently rapidly infused using a standard pressure bag along with the addition of maintenance fluids to maintain blood pressure. Hemodynamic parameters were recorded every 10 minutes and additionally at critical time points defined in the protocol. Primary end points included immediate hemostasis upon release of manual pressure (T0), hemostasis at 60 minutes, and rebleeding during the 60-minute observation period. RESULTS: NS was statistically superior to CG in a 5.5 mm traumatic hemorrhage model at T0 for immediate hemostasis (p=.0475), duration of application time (p=.0093), use of resuscitative fluids (p=.0042) and additional blood loss after application (p=.0385). NS and CG were statistically equivalent for hemostasis at 60 minutes, rebleeding during the study, and the additional secondary metrics, although the trend indicated that in a larger sample size, NS could prove statistical superiority in selected categories. CONCLUSIONS: In this porcine model of uncontrolled hemorrhage, NS improved immediate hemorrhage control, stability, and use of fluid in a 60-minute severe porcine hemorrhage model. In this study, NS demonstrated equivalence to CG at achieving long-term hemostasis and the prevention of rebleed after application. NS was shown to be an efficacious choice for hemorrhage control in combat and civilian emergency medical service environments.