Identification of Bone Marrow Cell Subpopulations Associated with Improved Functional Outcomes in Patients with Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial
In the current study, we sought to identify bone marrow-derived mononuclear cell (BM-MNC) subpopulations associated with a combined improvement in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and maximal oxygen consumption (VO 2 max) in patients with chron...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2016-09-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368915X689901 |
| _version_ | 1828886584418631680 |
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| author | Doris A. Taylor Emerson C. Perin James T. Willerson Claudia Zierold Micheline Resende Marjorie Carlson Belinda Nestor Elizabeth Wise Aaron Orozco Carl J. Pepine Timothy D. Henry Stephen G. Ellis David X. M. Zhao Jay H. Traverse John P. Cooke Robert C. Schutt Aruni Bhatnagar Maria B. Grant Dejian Lai Brian H. Johnstone Shelly L. Sayre Lem Moyé Ray F. Ebert Roberto Bolli Robert D. Simari |
| author_facet | Doris A. Taylor Emerson C. Perin James T. Willerson Claudia Zierold Micheline Resende Marjorie Carlson Belinda Nestor Elizabeth Wise Aaron Orozco Carl J. Pepine Timothy D. Henry Stephen G. Ellis David X. M. Zhao Jay H. Traverse John P. Cooke Robert C. Schutt Aruni Bhatnagar Maria B. Grant Dejian Lai Brian H. Johnstone Shelly L. Sayre Lem Moyé Ray F. Ebert Roberto Bolli Robert D. Simari |
| author_sort | Doris A. Taylor |
| collection | DOAJ |
| description | In the current study, we sought to identify bone marrow-derived mononuclear cell (BM-MNC) subpopulations associated with a combined improvement in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and maximal oxygen consumption (VO 2 max) in patients with chronic ischemic cardiomyopathy 6 months after receiving transendocardial injections of autologous BM-MNCs or placebo. For this prospectively planned analysis, we conducted an embedded cohort study comprising 78 patients from the FOCUS-Cardiovascular Cell Therapy Research Network (CCTRN) trial. Baseline BM-MNC immunophenotypes and progenitor cell activity were determined by flow cytometry and colony-forming assays, respectively. Previously stable patients who demonstrated improvement in LVEF, LVESV, and VO 2 max during the 6-month course of the FOCUS-CCTRN study (group 1, n = 17) were compared to those who showed no change or worsened in one to three of these endpoints (group 2, n = 61) and to a subset of patients from group 2 who declined in all three functional endpoints (group 2A, n = 11). Group 1 had higher frequencies of B-cell and CXCR4 + BM-MNC subpopulations at study baseline than group 2 or 2A. Furthermore, patients in group 1 had fewer endothelial colony-forming cells and monocytes/macrophages in their bone marrow than those in group 2A. To our knowledge, this is the first study to show that in patients with ischemic cardiomyopathy, certain bone marrow-derived cell subsets are associated with improvement in LVEF, LVESV, and VO 2 max at 6 months. These results suggest that the presence of both progenitor and immune cell populations in the bone marrow may influence the natural history of chronic ischemic cardiomyopathy—even in stable patients. Thus, it may be important to consider the bone marrow composition and associated regenerative capacity of patients when assigning them to treatment groups and evaluating the results of cell therapy trials. |
| first_indexed | 2024-12-13T11:48:24Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-13T11:48:24Z |
| publishDate | 2016-09-01 |
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| series | Cell Transplantation |
| spelling | doaj.art-4cf4483e0be94e109821143e6091df9e2022-12-21T23:47:27ZengSAGE PublishingCell Transplantation0963-68971555-38922016-09-012510.3727/096368915X689901Identification of Bone Marrow Cell Subpopulations Associated with Improved Functional Outcomes in Patients with Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN TrialDoris A. Taylor0Emerson C. Perin1James T. Willerson2Claudia Zierold3Micheline Resende4Marjorie Carlson5Belinda Nestor6Elizabeth Wise7Aaron Orozco8Carl J. Pepine9Timothy D. Henry10Stephen G. Ellis11David X. M. Zhao12Jay H. Traverse13John P. Cooke14Robert C. Schutt15Aruni Bhatnagar16Maria B. Grant17Dejian Lai18Brian H. Johnstone19Shelly L. Sayre20Lem Moyé21Ray F. Ebert22Roberto Bolli23Robert D. Simari24 Texas Heart Institute, CHI St. Luke's Health, Houston, TX, USATexas Heart Institute, CHI St. Luke's Health, Houston, TX, USATexas Heart Institute, CHI St. Luke's Health, Houston, TX, USAUniversity of Minnesota School of Medicine, Minneapolis, MN, USATexas Heart Institute, CHI St. Luke's Health, Houston, TX, USAUniversity of Minnesota School of Medicine, Minneapolis, MN, USATexas Heart Institute, CHI St. Luke's Health, Houston, TX, USAUniversity of Florida College of Medicine, Gainesville, FL, USATexas Heart Institute, CHI St. Luke's Health, Houston, TX, USAUniversity of Florida College of Medicine, Gainesville, FL, USAMinneapolis Heart Institute Foundation at Abbott, Minneapolis, MN, USACleveland Clinic Foundation, Cleveland, OH, USAWake Forest School of Medicine, Winston-Salem, NC, USAMinneapolis Heart Institute Foundation at Abbott, Minneapolis, MN, USAHouston Methodist Research Institute, Houston, TX, USAHouston Methodist Research Institute, Houston, TX, USAUniversity of Louisville, Louisville, KY, USAUniversity of Florida College of Medicine, Gainesville, FL, USAUniversity of Texas School of Public Health, Houston, TX, USAIndiana University School of Medicine, Indianapolis, IN, USAUniversity of Texas School of Public Health, Houston, TX, USAUniversity of Texas School of Public Health, Houston, TX, USANational Heart, Lung, and Blood Institute, Bethesda, MD, USAUniversity of Louisville, Louisville, KY, USAUniversity of Kansas School of Medicine, Kansas City, KS, USAIn the current study, we sought to identify bone marrow-derived mononuclear cell (BM-MNC) subpopulations associated with a combined improvement in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and maximal oxygen consumption (VO 2 max) in patients with chronic ischemic cardiomyopathy 6 months after receiving transendocardial injections of autologous BM-MNCs or placebo. For this prospectively planned analysis, we conducted an embedded cohort study comprising 78 patients from the FOCUS-Cardiovascular Cell Therapy Research Network (CCTRN) trial. Baseline BM-MNC immunophenotypes and progenitor cell activity were determined by flow cytometry and colony-forming assays, respectively. Previously stable patients who demonstrated improvement in LVEF, LVESV, and VO 2 max during the 6-month course of the FOCUS-CCTRN study (group 1, n = 17) were compared to those who showed no change or worsened in one to three of these endpoints (group 2, n = 61) and to a subset of patients from group 2 who declined in all three functional endpoints (group 2A, n = 11). Group 1 had higher frequencies of B-cell and CXCR4 + BM-MNC subpopulations at study baseline than group 2 or 2A. Furthermore, patients in group 1 had fewer endothelial colony-forming cells and monocytes/macrophages in their bone marrow than those in group 2A. To our knowledge, this is the first study to show that in patients with ischemic cardiomyopathy, certain bone marrow-derived cell subsets are associated with improvement in LVEF, LVESV, and VO 2 max at 6 months. These results suggest that the presence of both progenitor and immune cell populations in the bone marrow may influence the natural history of chronic ischemic cardiomyopathy—even in stable patients. Thus, it may be important to consider the bone marrow composition and associated regenerative capacity of patients when assigning them to treatment groups and evaluating the results of cell therapy trials.https://doi.org/10.3727/096368915X689901 |
| spellingShingle | Doris A. Taylor Emerson C. Perin James T. Willerson Claudia Zierold Micheline Resende Marjorie Carlson Belinda Nestor Elizabeth Wise Aaron Orozco Carl J. Pepine Timothy D. Henry Stephen G. Ellis David X. M. Zhao Jay H. Traverse John P. Cooke Robert C. Schutt Aruni Bhatnagar Maria B. Grant Dejian Lai Brian H. Johnstone Shelly L. Sayre Lem Moyé Ray F. Ebert Roberto Bolli Robert D. Simari Identification of Bone Marrow Cell Subpopulations Associated with Improved Functional Outcomes in Patients with Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial Cell Transplantation |
| title | Identification of Bone Marrow Cell Subpopulations Associated with Improved Functional Outcomes in Patients with Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial |
| title_full | Identification of Bone Marrow Cell Subpopulations Associated with Improved Functional Outcomes in Patients with Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial |
| title_fullStr | Identification of Bone Marrow Cell Subpopulations Associated with Improved Functional Outcomes in Patients with Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial |
| title_full_unstemmed | Identification of Bone Marrow Cell Subpopulations Associated with Improved Functional Outcomes in Patients with Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial |
| title_short | Identification of Bone Marrow Cell Subpopulations Associated with Improved Functional Outcomes in Patients with Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial |
| title_sort | identification of bone marrow cell subpopulations associated with improved functional outcomes in patients with chronic left ventricular dysfunction an embedded cohort evaluation of the focus cctrn trial |
| url | https://doi.org/10.3727/096368915X689901 |
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