Over expression of HIF-1α in human mesenchymal stem cells increases their supportive functions for hematopoietic stem cells in an experimental co-culture model

Introduction

Bone marrow transplantation is a critical approach for the treatment of many hematological disorders. Success of this approach is dependent on many factors the most important of which is the number of hematopoietic stem cells along with an efficient stroma. Co-transplantation of efficient mesenchymal stem cells can greatly improve the outcome of transplantations. Current researches assign a critical role for hypoxia inducible factor (HIF)-1α in protection of various cells and tissues probably through induction of cytokines. To make this feature applicable to human bone marrow-derived mesenchymal stem cells, we manipulated these cells to over express HIF-1α gene.

Materials and methods

Full-length cDNA of human HIF-1α was inserted into human bone marrow mesenchymal stem cells by pcDNA.3.1 non-viral plasmid vector, and the effect of this over expression on production of some hematopoietic growth factors was explored. Moreover, using a co-culture system, the interactive impact of HIF-1α-overexpressed mesenchymal stem cells on hematopoietic stem cells was evaluated.

Results

Over expression of HIF-1α in mesenchymal stem cells in normoxia increased production of one of the most important hematopoietic growth factors, Stem cell factor (also known as Steel factor or c-kit ligand). HIF-1α overexpression had no effect on production of other hematopoietic growth factors. In co-culture of mesenchymal stem cells-HIF-1α with hematopoietic stem cells, enhancement of colony formation and reduced differentiation of hematopoietic stem cells were observed.

Conclusion

Over expression of HIF-1α in human bone marrow-derived mesenchymal stem cells can augment the production of some hematopoietic growth factors, and we suggest this response of mesenchymal stem cells could help to improve the outcome of bone marrow transplantation.     

Appropriateness of invasive cardiovascular interventions in German hospitals (2000-2001): an evaluation using the RAND appropriateness criteria.

OBJECTIVE: Germany has the highest per capita rate of percutaneous transluminal coronary angioplasties (PTCAs) in Europe and the third highest per capita rate of heart surgeries requiring a heart-lung machine. The goal of this study was to evaluate the appropriateness of PTCA, coronary artery bypass graft (CABG), and carotid endarterectomy (CEA) in German hospitals using RAND appropriateness criteria. METHODS: A retrospective study in 121 randomly selected German hospitals (52% of all hospitals contacted) was performed from December 2000 to August 2001. A total of 361 patients were enrolled providing information on the appropriateness of 128 PTCAs, 92 CABGs, and 141 CEAs. RESULTS: Inappropriateness rates were 2% (95% CI 0-5%), 4% (95% CI 1-9%), and 3% (95% CI 1-7%) for PTCA, CABG, and CEA, respectively. The overall rate of uncertain procedures was 42% (95% CI 36-47%). Only 38% (95% CI 32-45%) of patients who received a coronary intervention had had a pre-interventional stress test. CONCLUSIONS: The study yielded little overt overuse in the performance of PTCAs, CABGs, and CEAs, but potentially large underuse of stress tests. Despite a high per capita rate of invasive cardiovascular interventions in Germany, the rate of inappropriate procedures was not larger than in other countries.     

Pulmorenales Syndrom bei einem Jugendlichen

Monatsschrift Kinderheilkunde -     

Infinite horizon linear quadratic tracking problem: A discounted cost function approach

The discounted cost function approach is one of the main approaches to the infinite time horizon problems in economics and market. This paper introduces a causal and optimal solution based on the discounted cost function approach for infinite horizon linear quadratic tracking problem with disturbance rejection and the problem of disturbance tracking by presenting the theoretical foundations. It is shown that the proposed method has the ability to solve the problems where the reference inputs and disturbance signals are not asymptotically stable. Two numerical examples, a grid connection of voltage source power electronic converter as a SISO system and a load frequency control of a 2‐area nonreheat thermal power system as a MIMO example, are presented to illustrate the effectiveness of the proposed method.