Key Points
- Identify the chemokine signals regulating mesenchymal stem cell (MSC) homing to infarcted myocardium after cardiac injury.
- Profiled temporal chemokine expression after myocardial infarction (MI) and matched profiles with chemokine receptors uniquely expressed on MSCs compared to cardiac fibroblasts.
- Overexpressed MCP-3 in hearts one month after MI and administered serial MSC infusions to evaluate homing, functional recovery, and cell differentiation.
- Identified MCP-3 as a selective homing factor whose overexpression one month after MI restored MSC recruitment to damaged myocardium.
- Serial infusions of MSCs improved cardiac function by 88.7% in MCP-3-expressing hearts (p < .001) compared with 8.6% in control hearts (p = .47).
- Engrafted MSCs did not differentiate into cardiac myocytes, instead promoting recovery through myofibroblast recruitment and collagen matrix remodeling.
Structured PICO
PPopulationMyocardial infarction model (preclinical)
IInterventionOverexpression of MCP-3 1 month after MI followed by serial infusions of mesenchymal stem cells (MSCs)
CComparatorControl hearts (without MCP-3 overexpression)
OOutcomeMSC homing to the heart and cardiac functionsurrogate
MCP-3 acts as a homing factor for mesenchymal stem cells, and its local overexpression recruits MSCs to injured myocardium, improving cardiac remodeling independent of myocyte regeneration.