Author + information
- Received February 10, 2009
- Revision received July 13, 2009
- Accepted August 21, 2009
- Published online October 1, 2009.
- Traci T. Goodchild, PhD⁎,†,
- Keith A. Robinson, PhD†,
- Wenxin Pang, MD⁎,†,
- Fernando Tondato, MD, PhD†,
- Jianhua Cui, MD†,
- Johnail Arrington, MS⁎,
- Lisa Godwin, AS†,
- Mark Ungs, BS, MBA⁎,
- Nadia Carlesso, MD, PhD‡,
- Nadine Weich, PhD⁎,
- Mark C. Poznansky, MD, PhD§ and
- Nicolas A.F. Chronos, MD⁎,†,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Nicolas A. F. Chronos, Saint Joseph's Research Institute, 5673 Peachtree-Dunwoody Road, Atlanta, Georgia 30342
Objectives In view of evidence that mature cells play a role in modulating the stem cell niche and thereby stem cell potential and proliferation, we hypothesized that a mature bone marrow (BM) mononuclear cell (MNC) infusion subfraction may have particular potency in promoting hematopoietic or resident stem cell-induced cardiac repair post-infarction.
Background Treatment of acute myocardial infarction (MI) with BM MNC infusion has shown promise for improving patient outcomes. However, clinical data are conflicting, and demonstrate modest improvements. BM MNCs consist of different subpopulations including stem cells, progenitors, and differentiated leukocytes.
Methods Stem cells (c-kit+) and subsets of mature cells including myeloid lineage, B and T-cells were isolated from bone marrow harvested from isogeneic donor rats. Recipient rats had baseline echocardiography then coronary artery ligation; 1 × 106 cells (enriched subpopulations or combinations of subpopulations of BM MNC) or saline was injected into ischemic and ischemic border zones. Cell subpopulations were either injected fresh or after overnight culture. After 2 weeks, animals underwent follow-up echocardiography. Cardiac tissue was assayed for cardiomyocyte proliferation and apoptosis.
Results Fractional ventricular diameter shortening was significantly improved compared with saline (38 ± 3.2%) when B cells alone were injected fresh (44 ± 3.0%, p = 0.035), or after overnight culture (51 ± 2.9%, p < 0.001), or after culture with c-kit+ cells (44 ± 2.4%, p = 0.062). B cells reduced apoptosis at 48 h after injection compared with control cells (5.7 ± 1.2% vs. 12.6 ± 2.0%, p = 0.005).
Conclusions Intramyocardial injection of B cells into early post-ischemic myocardium preserved cardiac function by cardiomyocyte salvage. Other BM MNC subtypes were either ineffective or suppressed cardioprotection conferred by an enriched B cell population.
Funding for this project was provided by AC Therapeutics, Norcross, Georgia, and The Jim Moran Foundation, Deerfield Beach, Florida. Drs. Chronos and Ungs are founders of AC Therapeutics and Drs. Goodchild and Pang and Johnail Arrington are or were employees of AC Therapeutics, Inc. Drs. Carlesso, Poznansky, and Weich are paid consultants for AC Therapeutics, Inc. Grant support for research was provided to Drs. Robinson, Tondato, and Cui by AC Therapeutics, Inc. Drs. Poznansky and Chronos contributed equally to this work.
- Received February 10, 2009.
- Revision received July 13, 2009.
- Accepted August 21, 2009.
- American College of Cardiology Foundation