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Open Access Research

The effect of bone marrow microenvironment on the functional properties of the therapeutic bone marrow-derived cells in patients with acute myocardial infarction

Johanna A Miettinen1*, Riikka J Salonen12, Kari Ylitalo1, Matti Niemelä1, Kari Kervinen1, Marjaana Säily1, Pirjo Koistinen1, Eeva-Riitta Savolainen3, Timo H Mäkikallio1, Heikki V Huikuri1 and Petri Lehenkari2

Author Affiliations

1 Department of Internal Medicine, Institute of Clinical Medicine, University of Oulu, P.O. Box 5000, Kajaanintie 50, Oulu FIN-90014, Finland

2 Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, P.O. Box 5000, Kajaanintie 50, Oulu FIN-90014, Finland

3 Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, P.O. Box 5000, Kajaanintie 50, Oulu FIN-90014, Finland

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Journal of Translational Medicine 2012, 10:66  doi:10.1186/1479-5876-10-66

Published: 2 April 2012

Abstract

Background

Treatment of acute myocardial infarction with stem cell transplantation has achieved beneficial effects in many clinical trials. The bone marrow microenvironment of ST-elevation myocardial infarction (STEMI) patients has never been studied even though myocardial infarction is known to cause an imbalance in the acid-base status of these patients. The aim of this study was to assess if the blood gas levels in the bone marrow of STEMI patients affect the characteristics of the bone marrow cells (BMCs) and, furthermore, do they influence the change in cardiac function after autologous BMC transplantation. The arterial, venous and bone marrow blood gas concentrations were also compared.

Methods

Blood gas analysis of the bone marrow aspirate and peripheral blood was performed for 27 STEMI patients receiving autologous stem cell therapy after percutaneous coronary intervention. Cells from the bone marrow aspirate were further cultured and the bone marrow mesenchymal stem cell (MSC) proliferation rate was determined by MTT assay and the MSC osteogenic differentiation capacity by alkaline phosphatase (ALP) activity assay. All the patients underwent a 2D-echocardiography at baseline and 4 months after STEMI.

Results

As expected, the levels of pO2, pCO2, base excess and HCO3 were similar in venous blood and bone marrow. Surprisingly, bone marrow showed significantly lower pH and Na+ and elevated K+ levels compared to arterial and venous blood. There was a positive correlation between the bone marrow pCO2 and HCO3 levels and MSC osteogenic differentiation capacity. In contrast, bone marrow pCO2 and HCO3 levels displayed a negative correlation with the proliferation rate of MSCs. Patients with the HCO3 level below the median value exhibited a more marked change in LVEF after BMC treatment than patients with HCO3 level above the median (11.13 ± 8.07% vs. 2.67 ± 11.89%, P = 0.014).

Conclusions

Low bone marrow pCO2 and HCO3 levels may represent the optimal environment for BMCs in terms of their efficacy in autologous stem cell therapy in STEMI patients.

Keywords:
Blood gas analysis; Bone marrow stem cells; Cell therapy; Mesenchymal stem cells; Myocardial infarction