Cited 259 times since 2009 (20.7 per year) source: Scopus JAMA, Volume 301, Issue 19, 1 1 2009, Pages 1997-2004 Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. van Ramshorst J, Bax JJ, Beeres SL, Dibbets-Schneider P, Roes SD, Stokkel MP, de Roos A, Fibbe WE, Zwaginga JJ, Boersma E, Schalij MJ, Atsma DE


Previous studies have suggested that bone marrow cell injection may improve myocardial perfusion and left ventricular (LV) function in patients with chronic myocardial ischemia.


To investigate the effect of intramyocardial bone marrow cell injection on myocardial perfusion and LV function in patients with chronic myocardial ischemia.

Design, setting, and patients

Randomized, double-blind, placebo-controlled trial at a Netherlands university hospital, May 1, 2005-March 3, 2008 (6-month follow-up ended September 2008) of 50 patients with chronic myocardial ischemia (mean age [SD], 64 [8] years; 43 men).

Inclusion criteria

severe angina pectoris despite optimal medical therapy and myocardial ischemia. All patients were ineligible for conventional revascularization.


Intramyocardial injection of 100 x 10(6) autologous bone marrow-derived mononuclear cells or placebo solution.

Main outcome measures

Primarily, the summed stress score, a 17-segment score for stress myocardial perfusion assessed by Tc-99m tetrofosmin single-photon emission computed tomography (SPECT). Secondary included LV ejection fraction (LVEF), Canadian Cardiovascular Society (CCS) class, and Seattle Angina Questionnaire quality-of-life score (mean difference >5% considered clinically significant).


After 3-month follow-up, the summed stress score (mean [SD]) improved from 23.5 (4.7) to 20.1 (4.6) (P < .001) in the bone marrow cell group, compared with a decrease from 24.8 (5.5) to 23.7 (5.4) (P = .004) in the placebo group. In the bone marrow cell-treated patients who underwent magnetic resonance imaging (MRI), a 3% absolute increase in LVEF was observed at 3 months (95% CI, 0.5% to 4.7%; n = 18), but the placebo group showed no improvement. CCS angina score improved significantly in the bone marrow cell group (6-month absolute difference, -0.79; 95% CI, -1.10 to -0.48; P < .001) compared with no significant improvement in the placebo group. Quality-of-life score increased from 56% (9%) to 64% (12%) at 3 months and 69% (12%) at 6 months in bone marrow cell-treated patients, compared with a smaller increase in the placebo group from 57% (11%) to 61% (14%) to 64% (17%). The improvements in CCS class and quality of life score were significantly greater in bone marrow cell-treated patients than in placebo-treated patients (P = .03 and P = .04, respectively).


In this short-term study of patients with chronic myocardial ischemia refractory to medical treatment, intramyocardial bone marrow cell injection resulted in a statistically significant but modest improvement in myocardial perfusion compared with placebo. Further studies are required to assess long-term results and efficacy for mortality and morbidity.

Trial registrations Identifier

NTR400 and Identifier


JAMA. 2009 5;301(19):1997-2004