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

Aruni Bhatnagar, Roberto Bolli, Brian H. Johnstone, Jay H. Traverse, Timothy D. Henry, Carl J. Pepine, James T. Willerson, Emerson C. Perin, Stephen G. Ellis, David X M Zhao, Phillip C. Yang, John P. Cooke, Robert C. Schutt, Barry H. Trachtenberg, Aaron Orozco, Micheline Resende, Ray F. Ebert, Shelly L. Sayre, Robert D. Simari, Lem MoyéChristopher R. Cogle, Doris A. Taylor

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 CD45dim/CD11bdim 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 CD11bdim 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+/CXCR4dim 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 CD11bdim 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.

Original languageEnglish (US)
Pages (from-to)142-150
Number of pages9
JournalAmerican Heart Journal
Volume179
DOIs
StatePublished - Sep 1 2016

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Cell- and Tissue-Based Therapy
Bone Marrow Cells
Research
Bone Marrow
Left Ventricular Function
Stroke Volume
Clinical Trials
Population
Bone Marrow Transplantation
C-Reactive Protein
Infarction
Body Mass Index
Multivariate Analysis
Cell Count
Smoking
Myocardial Infarction
Hypertension
Transplants
Phenotype
Growth

ASJC Scopus subject areas

  • Medicine(all)
  • Cardiology and Cardiovascular Medicine

Cite this

Bone marrow cell characteristics associated with patient profile and cardiac performance outcomes in the LateTIME-Cardiovascular Cell Therapy Research Network (CCTRN) trial. / Bhatnagar, Aruni; Bolli, Roberto; Johnstone, Brian H.; Traverse, Jay H.; Henry, Timothy D.; Pepine, Carl J.; Willerson, James T.; Perin, Emerson C.; Ellis, Stephen G.; Zhao, David X M; Yang, Phillip C.; Cooke, John P.; Schutt, Robert C.; Trachtenberg, Barry H.; Orozco, Aaron; Resende, Micheline; Ebert, Ray F.; Sayre, Shelly L.; Simari, Robert D.; Moyé, Lem; Cogle, Christopher R.; Taylor, Doris A.

In: American Heart Journal, Vol. 179, 01.09.2016, p. 142-150.

Research output: Contribution to journalArticle

Bhatnagar, A, Bolli, R, Johnstone, BH, Traverse, JH, Henry, TD, Pepine, CJ, Willerson, JT, Perin, EC, Ellis, SG, Zhao, DXM, Yang, PC, Cooke, JP, Schutt, RC, Trachtenberg, BH, Orozco, A, Resende, M, Ebert, RF, Sayre, SL, Simari, RD, Moyé, L, Cogle, CR & Taylor, DA 2016, 'Bone marrow cell characteristics associated with patient profile and cardiac performance outcomes in the LateTIME-Cardiovascular Cell Therapy Research Network (CCTRN) trial', American Heart Journal, vol. 179, pp. 142-150. https://doi.org/10.1016/j.ahj.2016.06.018
Bhatnagar, Aruni ; Bolli, Roberto ; Johnstone, Brian H. ; Traverse, Jay H. ; Henry, Timothy D. ; Pepine, Carl J. ; Willerson, James T. ; Perin, Emerson C. ; Ellis, Stephen G. ; Zhao, David X M ; Yang, Phillip C. ; Cooke, John P. ; Schutt, Robert C. ; Trachtenberg, Barry H. ; Orozco, Aaron ; Resende, Micheline ; Ebert, Ray F. ; Sayre, Shelly L. ; Simari, Robert D. ; Moyé, Lem ; Cogle, Christopher R. ; Taylor, Doris A. / Bone marrow cell characteristics associated with patient profile and cardiac performance outcomes in the LateTIME-Cardiovascular Cell Therapy Research Network (CCTRN) trial. In: American Heart Journal. 2016 ; Vol. 179. pp. 142-150.
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abstract = "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 CD45dim/CD11bdim 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 CD11bdim 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+/CXCR4dim 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 CD11bdim 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.",
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AU - Bhatnagar, Aruni

AU - Bolli, Roberto

AU - Johnstone, Brian H.

AU - Traverse, Jay H.

AU - Henry, Timothy D.

AU - Pepine, Carl J.

AU - Willerson, James T.

AU - Perin, Emerson C.

AU - Ellis, Stephen G.

AU - Zhao, David X M

AU - Yang, Phillip C.

AU - Cooke, John P.

AU - Schutt, Robert C.

AU - Trachtenberg, Barry H.

AU - Orozco, Aaron

AU - Resende, Micheline

AU - Ebert, Ray F.

AU - Sayre, Shelly L.

AU - Simari, Robert D.

AU - Moyé, Lem

AU - Cogle, Christopher R.

AU - Taylor, Doris A.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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 CD45dim/CD11bdim 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 CD11bdim 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+/CXCR4dim 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 CD11bdim 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.

AB - 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 CD45dim/CD11bdim 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 CD11bdim 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+/CXCR4dim 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 CD11bdim 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.

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