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Bone marrow cell characteristics associated with patient profile and cardiac performance outcomes in the
Aruni Bhatnagar1, Roberto Bolli1, Brian H Johnstone2
1University of Louisville, Louisville, KY.
Insights
Specific bone marrow cell (BMC) subpopulations, like CD133(+) and CD34(+) cells, are linked to better heart function recovery after myocardial infarction. Conversely, higher CD11b(dim) cells are associated with worse outcomes in cardiac repair.
Area of Science:
- Cardiology
- Regenerative Medicine
- Hematology
Background:
- Preclinical studies suggest bone marrow cell (BMC) transplantation aids cardiac recovery post-myocardial infarction.
- Clinical trials using unfractionated bone marrow show variable improvements in cardiac function.
Purpose of the Study:
- To investigate if specific BMC subpopulations correlate with functional recovery in post-myocardial infarction patients.
- To examine the association between BMC phenotypes and left ventricular (LV) function in the LateTIME-CCTRN trial.
Main Methods:
- Analyzed BMC subpopulations in relation to patient characteristics (age, BMI, hypertension, C-reactive protein, smoking).
- Assessed the association between BMC composition and changes in LV ejection fraction and wall motion.
- Utilized multivariate analysis to identify predictive BMC markers for cardiac function recovery.
Main Results:
- Older individuals had higher CD133(+) and CD3(+) cells. Hypertension and high C-reactive protein correlated with more CD133(+) cells.
- CD11b(dim) cells showed a negative association with LV ejection fraction and wall motion changes.
- CD133(+), CD34(+), and CD45(+)/CXCR4(dim) cells, along with faster endothelial colony forming assay growth rates, were positively associated with LV ejection fraction improvement.
Conclusions:
- Bone marrow composition varies with patient characteristics and influences cardiac recovery post-myocardial infarction.
- Higher abundance of CD133(+) and CD34(+) cells in bone marrow is linked to better LV function recovery.
- Bone marrow phenotype may predict clinical response to BMC therapy, suggesting potential for targeted cell selection in future trials.
Background:
Although several preclinical studies have shown that bone marrow cell (BMC) transplantation promotes cardiac recovery after myocardial infarction, clinical trials with unfractionated bone marrow have shown variable improvements in cardiac function.
Methods:
To determine whether in a population of post-myocardial infarction patients, functional recovery after BM transplant is associated with specific BMC subpopulation, we examined the association between BMCs with left ventricular (LV) function in the LateTIME-CCTRN trial.
Results:
In this population, we found that older individuals had higher numbers of BM CD133(+) and CD3(+) cells. Bone marrow from individuals with high body mass index had lower CD45(dim)/CD11b(dim) levels, whereas those with hypertension and higher C-reactive protein levels had higher numbers of CD133(+) cells. Smoking was associated with higher levels of CD133(+)/CD34(+)/VEGFR2(+) cells and lower levels of CD3(+) cells. Adjusted multivariate analysis indicated that CD11b(dim) cells were negatively associated with changes in LV ejection fraction and wall motion in both the infarct and border zones. Change in LV ejection fraction was positively associated with CD133(+), CD34(+), and CD45(+)/CXCR4(dim) cells as well as faster BMC growth rates in endothelial colony forming assays.
Conclusions:
In the LateTIME population, BM composition varied with patient characteristics and treatment. Irrespective of cell therapy, recovery of LV function was greater in patients with greater BM abundance of CD133(+) and CD34(+) cells and worse in those with higher levels of CD11b(dim) cells. Bone marrow phenotype might predict clinical response before BMC therapy and administration of selected BM constituents could potentially improve outcomes of other future clinical trials.