Abstract 1420: Donor Aging or Myocardial Infarction Impairs Bone Marrow Cell Therapy for the Infarcted Heart
Human and animal experiments involving delivery of bone marrow cells (BMCs) to infarcted hearts have suggested that BMCs may have therapeutic effects. However, animal experiments typically involve BMCs from young, healthy donors and may poorly represent clinical autologous cell therapy, in which delivered cells are from older myocardial infarction (MI) patients. We hypothesized that donor age or MI would impair BMC therapeutic efficacy regardless of the age of the recipient heart. To test this, we implanted BMCs from healthy or infarcted mice of 3 different ages into infarcted hearts under ultrasound guidance at 3 days post-MI, a time comparable to that used in clinical trials. Recipient 10-week-young mice were subjected to MI by permanent left coronary artery ligation. Donor BMCs were harvested from healthy mice or 3 day post-MI mice, at ages of 10 weeks (young), 1 year (middle-aged), and 2 years (old); with a vehicle control (HBSS). In all groups, left ventricular ejection fraction (EF) declined uniformly from a baseline of 57±5% (SD) to 34±5% at day 2 post-MI. Injection of HBSS permitted continued deterioration of EF to 22±5% at day 28. In contrast, young and middle-aged healthy donor BMCs preserved EF (36±7% and 33±7%). Notably, EF in the young infarcted and middle-aged infarcted donor groups declined (31±6% and 27±9%) and day 28 EF in the middle-aged infarcted group was not significantly different from HBSS. Old healthy and old infarcted donor BMCs led to a decline in EF (24±4% and 21±4%) comparable to the negative control, despite good viability in all BMCs. Our findings suggest that therapeutic efficacy of BMCs from old or infarcted donors is impaired.