Heart Failure Impairs Bone Marrow Hematopoietic Stem Cell Function and Responses to Injury

Area of Science:

• Hematology
• Cardiology
• Stem Cell Biology

Background:

• Heart failure (HF) is characterized by myocardial dysfunction and systemic inflammation.
• Chronic inflammation associated with HF may impact bone marrow (BM) stem cell renewal and differentiation.
• The effects of HF on BM stem/progenitor cells are not well understood.

Purpose of the Study:

• To investigate the impact of heart failure on bone marrow stem and progenitor cell function.
• To assess alterations in cell composition and reconstitution potential in HF patients' BM.
• To evaluate the effects of HF-altered BM on tissue repair responses.

Main Methods:

• Murine model of myocardial infarction (MI) using EGFP+ mice to assess BM reconstitution potential.
• Analysis of BM from 71 human subjects (20 HF, 51 controls) including cell composition and colony formation.
• Xenotransplantation of human CD34+ cells from HF patients into NOD-SCID-IL2rγnull mice.
• Assessment of tissue repair responses in reconstituted mice post-MI.

Main Results:

• BM from MI mice showed reduced reconstitution potential compared to sham mice.
• HF patients exhibited increased circulating myeloid cells and altered BM cell composition and colony formation.
• Mice engrafted with HF-BM had significantly fewer human CD34+ cells and reduced lymphoid production.
• HF-BM reconstituted mice showed reduced survival and altered cellular responses after MI.

Conclusions:

• Heart failure significantly alters bone marrow composition and function.
• HF adversely affects hematopoietic stem cell reconstitution potential.
• HF impacts cellular responses to injury, suggesting a role for BM dysfunction in disease progression.