Bone marrow cell characteristics associated with patient profile and cardiac performance outcomes in the LateTIME-Cardiovascular Cell Therapy Research Network (CCTRN) trial

Am Heart J. 2016 Sep;179:142-50. doi: 10.1016/j.ahj.2016.06.018. Epub 2016 Jul 6.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00684060.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AC133 Antigen / metabolism
  • Adult
  • Aged
  • Antigens, CD34 / metabolism
  • Body Mass Index
  • Bone Marrow Cells / metabolism
  • Bone Marrow Transplantation*
  • C-Reactive Protein / metabolism
  • CD11b Antigen / metabolism
  • Cohort Studies
  • Female
  • Humans
  • Hypertension / metabolism
  • Leukocyte Common Antigens / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Obesity / metabolism
  • Prospective Studies
  • Receptors, CXCR4 / metabolism
  • Recovery of Function*
  • Smoking / metabolism
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Dysfunction, Left / therapy*
  • Ventricular Function, Left

Substances

  • AC133 Antigen
  • Antigens, CD34
  • CD11b Antigen
  • CXCR4 protein, human
  • ITGAM protein, human
  • PROM1 protein, human
  • Receptors, CXCR4
  • C-Reactive Protein
  • Leukocyte Common Antigens
  • PTPRC protein, human

Associated data

  • ClinicalTrials.gov/NCT00684060