Abstract 17792: Impaired Efficacy of Bone Marrow Cell Therapy for Myocardial Infarction Reflects Decreasing Bone Marrow B Cells with Advancing Age
Introduction: Implantation of unfractionated bone marrow cells (BMCs) into mouse hearts post-myocardial infarction (MI) can prevent a decline in cardiac function. However, clinical trials of BMC therapy have been less successful. While most mouse experiments use young healthy BMC donors, MI patients undergoing autologous cell therapy (i.e., receiving their own BMCs) are older and are post-MI. We reported previously that BMCs from old mice, or from mice that are themselves post-MI, are impaired in this therapeutic capacity; and that inflammation caused by donor MI mediates impairment of BMC therapeutic potential. As an indication of ongoing inflammation, we reported reduced levels of B cells in post-MI BMCs.
Hypothesis: Because B cells have been reported to be a therapeutic subpopulation of BMCs, we asked whether B cell changes in bone marrow may account for the reduced therapeutic potential of BMCs from post-MI and/or aged donors.
Methods: We induced permanent coronary artery ligation MI, and injected 106 BMCs per heart by ultrasound guidance into the infarct border zone 3 days post-MI. Recipient mice were always young (10-12 weeks) while BMC donors varied in age. Echocardiography was performed before MI, 2 days post-MI (the day before injection), and 28 days post-MI.
Results: Injection of BMCs from donors of increasing ages (10 weeks, 6 months, and 1, 1.5, and 2 years) resulted in progressively lower day 28 recipient left ventricular ejection fraction (EF; Fig. 1a); and larger end systolic and diastolic chamber volumes, lower wall thickness, and larger infarct size (not shown). FACS analysis revealed fewer B cells in aged donor BMCs (Fig. 1b). Young healthy donor BMCs became less therapeutic when manually depleted of B cells (Fig. 1c).
Conclusions: Donor age or MI lowers the number of bone marrow B cells, resulting in a less therapeutic BMC population. Our findings may partially explain why clinical trials of BMC therapy for MI have led to more modest results than mouse studies.
Author Disclosures: S. An: None. X. Wang: None. M.A. Ruck: None. D.S. Kostyushev: None. M. Varga: None. S.V. Suchkov: None. S. Kogan: None. M.L. Hermiston: None. M.L. Springer: None.
- © 2014 by American Heart Association, Inc.