Therapeutic strategy towards renal restoration in chronic kidney disease.

Background: The population with end-stage renal disease is increasing. This continued growth is related to: i) diagnostic failure in screening for early chronic kidney disease (CKD) associated with tubulointerstitial fibrosis (TIF), ii) failure in preventing renal disease progression due to lack of understanding of the precise determinants that induce TIF, and iii) delayed treatment which simply slows renal disease progression, but is unable to restore renal function. Objective: To review therapeutic strategy to restore renal function in CKD stressing fractional excretion of magnesium (FE Mg) as a sensitive biomarker for screening early CKD associated with TIF. Results: There is much evidence to support the crucial role of renal microvascular disease as the determinant of TIF and disease progression. A unique pattern of hemodynamic maladjustment is characterized by a preferential constriction of the efferent arteriole that induces peritubular capillary flow reduction in CKDs. Conclusion: The present information leads to a therapeutic strategy to restore renal function in early CKD patients.

Increased smooth muscle actin expression from bone marrow stromal cells under retinoic acid treatment: an attempt for autologous blood vessel tissue engineering.

Vascular replacement in vital organs is sometimes necessary for human life for example because of atherosclerosis. Blood vessel tissue engineering is applied for autologous transplantations to avoid graft rejections. Stem cells are used for blood vessel tissue engineering because they are the origin of smooth muscle cells, endothelial cells and fibroblasts. This paper shows that bone marrow stromal cells (BMSCs) can be induced to differentiate into the early stage of smooth muscle cells by using 0.01 microM retinoic acid. The differentiation of BMSCs to smooth muscle cells was detected by the expression of smooth muscle alpha actin (SM alpha-actin), the earliest smooth muscle cell marker. The SM alpha-actin marker expression was demonstrated using indirect immunofluorescence technique and Western blot analysis. The induction of BMSC to form early stages of smooth muscle cells in this study is appropriate for blood vessel tissue engineering because the early stage smooth muscle cells may be stimulated to develop vascular walls with endothelial cells using a co-culture system.

Enhanced maturation and proliferation of beta-thalassemia/Hb E erythroid precursor cells in culture.

Upon erythroid cell maturation in vivo, beta-thalassemic erythroid cells accumulate unmatched unstable alpha-globin chains that are believed to be a causal factor in such cell destruction. This study showed that beta-thalassemia/Hb E erythroid precursor cells from peripheral blood had accelerated maturation, and could mature to the terminal erythroid stage. During the early period of cell culture, erythroid precursor cells derived from subjects with the more severe form of beta-thalassemia/Hb E had higher rate of erythroid maturation. In addition, peripheral blood mononuclear cells from beta-thalassemia/Hb E subjects had higher erythroid proliferative potential than cells derived from normal controls. Erythroid proportion in the more severe beta-thalassemia/Hb E cases was less than that of the milder cases. Premature apoptosis was not observed during the 15 days of erythroid cell culture from both beta-thalassemia/Hb E and normal subjects.