PGY2 Internal Medicine University of Toronto University of Toronto
Disclosure(s):
Tina Marvasti, MD, PhD: No financial relationships to disclose
Background: Heart failure (HF) is a clinical syndrome associated with a progressive decline in myocardial function and low-grade systemic inflammation. Chronic inflammation can have lasting effects on the bone marrow (BM) stem cell pool by impacting cell renewal and lineage differentiation. However, how HF affects BM stem/progenitor cells remains largely unexplored.
METHODS AND RESULTS: EGFP+ mice were subjected to coronary artery ligation and BM collected eight weeks post-myocardial infarction (MI). Transplant of EGFP+ BM into WT mice revealed reduced reconstitution potential of BM from mice subjected to MI vs. BM from sham mice. To study the effects HF has on human BM function, seventy-one patients, HF (n=20) and control (n=51), who were scheduled for elective cardiac surgery were consented and enrolled in this study. HF patients exhibited more circulating blood myeloid cells and analysis of patient BM revealed significant differences in cell composition and colony formation potential. Human CD34+ cell reconstitution potential was also assessed using the NSG mouse xenotransplant model. NSG mice reconstituted with HF patient BM had significantly fewer engrafted human CD34+ cells as well as reduced lymphoid cell production. Analysis of tissue repair responses using permanent LAD ligation demonstrated reduced survival of HF-BM reconstituted mice as well as significant differences in human (donor) and mouse (host) cellular responses post-myocardial infarction.
Conclusion: HF alters the BM composition, adversely affects cell reconstitution potential, and alters cellular responses to injury. Further studies are needed to determine whether restoring BM function can impact disease progression or improve cellular responses to injury.
