Bone Marrow-Derived B Cells Preserve Ventricular Function After Acute Myocardial Infarction

Traci T. Goodchild, Keith A. Robinson, Wenxin Pang, Fernando Tondato, Jianhua Cui, Johnail Arrington, Lisa Godwin, Mark Ungs, Nadia Carlesso, Nadine Weich, Mark C. Poznansky, Nicolas A F Chronos

Research output: Contribution to journalArticle

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Abstract

Objectives: In view of evidence that mature cells play a role in modulating the stem cell niche and thereby stem cell potential and proliferation, we hypothesized that a mature bone marrow (BM) mononuclear cell (MNC) infusion subfraction may have particular potency in promoting hematopoietic or resident stem cell-induced cardiac repair post-infarction. Background: Treatment of acute myocardial infarction (MI) with BM MNC infusion has shown promise for improving patient outcomes. However, clinical data are conflicting, and demonstrate modest improvements. BM MNCs consist of different subpopulations including stem cells, progenitors, and differentiated leukocytes. Methods: Stem cells (c-kit+) and subsets of mature cells including myeloid lineage, B and T-cells were isolated from bone marrow harvested from isogeneic donor rats. Recipient rats had baseline echocardiography then coronary artery ligation; 1 × 106 cells (enriched subpopulations or combinations of subpopulations of BM MNC) or saline was injected into ischemic and ischemic border zones. Cell subpopulations were either injected fresh or after overnight culture. After 2 weeks, animals underwent follow-up echocardiography. Cardiac tissue was assayed for cardiomyocyte proliferation and apoptosis. Results: Fractional ventricular diameter shortening was significantly improved compared with saline (38 ± 3.2%) when B cells alone were injected fresh (44 ± 3.0%, p = 0.035), or after overnight culture (51 ± 2.9%, p < 0.001), or after culture with c-kit+ cells (44 ± 2.4%, p = 0.062). B cells reduced apoptosis at 48 h after injection compared with control cells (5.7 ± 1.2% vs. 12.6 ± 2.0%, p = 0.005). Conclusions: Intramyocardial injection of B cells into early post-ischemic myocardium preserved cardiac function by cardiomyocyte salvage. Other BM MNC subtypes were either ineffective or suppressed cardioprotection conferred by an enriched B cell population.

Original languageEnglish
Pages (from-to)1005-1016
Number of pages12
JournalJACC: Cardiovascular Interventions
Volume2
Issue number10
DOIs
StatePublished - Oct 2009

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Ventricular Function
B-Lymphocytes
Bone Marrow Cells
Bone Marrow
Myocardial Infarction
Stem Cells
Cardiac Myocytes
Echocardiography
Apoptosis
Stem Cell Niche
Injections
Myeloid Cells
Infarction
Ligation
Coronary Vessels
Myocardium
Leukocytes
Cell Proliferation
Tissue Donors
T-Lymphocytes

Keywords

  • cell therapy
  • myocardial infarction
  • myocardial repair
  • regenerative medicine
  • stem cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Goodchild, T. T., Robinson, K. A., Pang, W., Tondato, F., Cui, J., Arrington, J., ... Chronos, N. A. F. (2009). Bone Marrow-Derived B Cells Preserve Ventricular Function After Acute Myocardial Infarction. JACC: Cardiovascular Interventions, 2(10), 1005-1016. https://doi.org/10.1016/j.jcin.2009.08.010

Bone Marrow-Derived B Cells Preserve Ventricular Function After Acute Myocardial Infarction. / Goodchild, Traci T.; Robinson, Keith A.; Pang, Wenxin; Tondato, Fernando; Cui, Jianhua; Arrington, Johnail; Godwin, Lisa; Ungs, Mark; Carlesso, Nadia; Weich, Nadine; Poznansky, Mark C.; Chronos, Nicolas A F.

In: JACC: Cardiovascular Interventions, Vol. 2, No. 10, 10.2009, p. 1005-1016.

Research output: Contribution to journalArticle

Goodchild, TT, Robinson, KA, Pang, W, Tondato, F, Cui, J, Arrington, J, Godwin, L, Ungs, M, Carlesso, N, Weich, N, Poznansky, MC & Chronos, NAF 2009, 'Bone Marrow-Derived B Cells Preserve Ventricular Function After Acute Myocardial Infarction', JACC: Cardiovascular Interventions, vol. 2, no. 10, pp. 1005-1016. https://doi.org/10.1016/j.jcin.2009.08.010
Goodchild, Traci T. ; Robinson, Keith A. ; Pang, Wenxin ; Tondato, Fernando ; Cui, Jianhua ; Arrington, Johnail ; Godwin, Lisa ; Ungs, Mark ; Carlesso, Nadia ; Weich, Nadine ; Poznansky, Mark C. ; Chronos, Nicolas A F. / Bone Marrow-Derived B Cells Preserve Ventricular Function After Acute Myocardial Infarction. In: JACC: Cardiovascular Interventions. 2009 ; Vol. 2, No. 10. pp. 1005-1016.
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abstract = "Objectives: In view of evidence that mature cells play a role in modulating the stem cell niche and thereby stem cell potential and proliferation, we hypothesized that a mature bone marrow (BM) mononuclear cell (MNC) infusion subfraction may have particular potency in promoting hematopoietic or resident stem cell-induced cardiac repair post-infarction. Background: Treatment of acute myocardial infarction (MI) with BM MNC infusion has shown promise for improving patient outcomes. However, clinical data are conflicting, and demonstrate modest improvements. BM MNCs consist of different subpopulations including stem cells, progenitors, and differentiated leukocytes. Methods: Stem cells (c-kit+) and subsets of mature cells including myeloid lineage, B and T-cells were isolated from bone marrow harvested from isogeneic donor rats. Recipient rats had baseline echocardiography then coronary artery ligation; 1 × 106 cells (enriched subpopulations or combinations of subpopulations of BM MNC) or saline was injected into ischemic and ischemic border zones. Cell subpopulations were either injected fresh or after overnight culture. After 2 weeks, animals underwent follow-up echocardiography. Cardiac tissue was assayed for cardiomyocyte proliferation and apoptosis. Results: Fractional ventricular diameter shortening was significantly improved compared with saline (38 ± 3.2{\%}) when B cells alone were injected fresh (44 ± 3.0{\%}, p = 0.035), or after overnight culture (51 ± 2.9{\%}, p < 0.001), or after culture with c-kit+ cells (44 ± 2.4{\%}, p = 0.062). B cells reduced apoptosis at 48 h after injection compared with control cells (5.7 ± 1.2{\%} vs. 12.6 ± 2.0{\%}, p = 0.005). Conclusions: Intramyocardial injection of B cells into early post-ischemic myocardium preserved cardiac function by cardiomyocyte salvage. Other BM MNC subtypes were either ineffective or suppressed cardioprotection conferred by an enriched B cell population.",
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AU - Cui, Jianhua

AU - Arrington, Johnail

AU - Godwin, Lisa

AU - Ungs, Mark

AU - Carlesso, Nadia

AU - Weich, Nadine

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