Positive Effects of Heme Oxygenase Upregulation on Adiposity and Vascular Dysfunction: Gene Targeting vs. Pharmacologic Therapy.

Objective: Heme oxygenase (HO-1) plays a critical role in adipogenesis and it is important to understand its function in obesity. Many studies have shown that upregulation of HO-1 can affect the biologic parameters in obesity-mediated diabetes, hypertension and vascular endothelial cell function. Thus, we aimed to explore the hypothesis that upregulation of HO-1, using a pharmacologic approach as well as gene targeting, would improve both adiposity and endothelial cell dysfunction by direct targeting of endothelial cells.

Measurement of cystatin C functional activity in the cerebrospinal fluid of amyotrophic lateral sclerosis and control subjects.

Background: Cystatin C is a constitutively expressed and abundant cysteine protease inhibitor within the cerebrospinal fluid (CSF). Recent studies have reported a significant reduction in cystatin C concentration in the CSF of patients with amyotrophic lateral sclerosis (ALS) and several other neurodegenerative diseases, relative to healthy controls. Cystatin C can exhibit both neuroprotective and neurotoxic properties, suggesting that altered CSF cystatin C concentrations could potentially impact the pathogenesis or progression of these disorders.

Cystatin C: a candidate biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurologic disease characterized by progressive motor neuron degeneration. Clinical disease management is hindered by both a lengthy diagnostic process and the absence of effective treatments. Reliable panels of diagnostic, surrogate, and prognostic biomarkers are needed to accelerate disease diagnosis and expedite drug development.

Marginal mass islet transplantation with autologous mesenchymal stem cells promotes long-term islet allograft survival and sustained normoglycemia.

Allogeneic islet transplantation is an option to treat diabetes however there are obstacles that are limiting its clinical use. We have examined whether mesenchymal stem cells (MSC) improve islet graft survival and whether such therapy allows for better graft acceptance with reduced requirement for immunosuppression. In vitro-expanded syngeneic bone marrow-derived MSC were co-transplanted with islets into omental pouch in a rat model of streptozotocin-induced diabetes.

Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia.

Cell-based therapies offer considerable promise for prevention or cure of diabetes. We explored the potential of autologous, self-renewing, mesenchymal stem cells (MSC) as a clinically-applicable approach to promote glucose homeostasis. In vitro-expanded syngeneic bone marrow-derived MSC were administered following or prior to diabetes induction into a rat model of streptozotocin-induced beta cell injury.