title: The effect of bone marrow microenvironment on the functional properties of the therapeutic bone marrow-derived cells in patients with acute myocardial infarction.
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 pO(2), pCO(2), base excess and HCO(3) 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 pCO(2) and HCO(3) levels and MSC osteogenic differentiation capacity. In contrast, bone marrow pCO(2) and HCO(3) levels displayed a negative correlation with the proliferation rate of MSCs. Patients with the HCO(3) level below the median value exhibited a more marked change in LVEF after BMC treatment than patients with HCO(3) level above the median (11.13 ± 8.07% vs. 2.67 ± 11.89%, P = 0.014).
  
  
  CONCLUSIONS
  Low bone marrow pCO(2) and HCO(3) levels may represent the optimal environment for BMCs in terms of their efficacy in autologous stem cell therapy in STEMI patients.
authors.affiliation: Department of Internal Medicine, Institute of Clinical Medicine, University of Oulu, Oulu FIN-90014, Finland. johanna.miettinen@oulu.fi
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Miettinen
authors.forename: Riikka J
authors.initials: RJ
authors.lastname: Salonen
authors.forename: Kari
authors.initials: K
authors.lastname: Ylitalo
authors.forename: Matti
authors.initials: M
authors.lastname: Niemelä
authors.forename: Kari
authors.initials: K
authors.lastname: Kervinen
authors.forename: Marjaana
authors.initials: M
authors.lastname: Säily
authors.forename: Pirjo
authors.initials: P
authors.lastname: Koistinen
authors.forename: Eeva-Riitta
authors.initials: ER
authors.lastname: Savolainen
authors.forename: Timo H
authors.initials: TH
authors.lastname: Mäkikallio
authors.forename: Heikki V
authors.initials: HV
authors.lastname: Huikuri
authors.forename: Petri
authors.initials: P
authors.lastname: Lehenkari
mesh_terms: D000328:Adult; D000368:Aged; D001784:Blood Gas Analysis; D001853:Bone Marrow / Q000098:blood supply; D001854:Bone Marrow Cells / Q000737:chemistry / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000502:physiology*; D002478:Cells, Cultured; D060833:Cellular Microenvironment / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D010865:Pilot Projects; D011379:Prognosis; D013318:Stroke Volume / Q000502:physiology; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult