Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model

Soon Jun Hong, Pamela I. Rogers, John Kihlken, Jessica Warfel, Chris Bull, Maja Deuter-Reinhard, Dongni Feng, Jie Xie, Aaron Kyle, Stephanie Merfeld-Clauss, Brian H. Johnstone, Dmitry O. Traktuev, Peng Sheng Chen, Jonathan Lindner, Keith L. March

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    Objectives The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery. Methods Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n-=-7), the single bolus group (SB) (n-=-7, 15 × 107 ASCs), or the divided dose group (DD) (n-=-7, 5 × 107 ASCs/day for three consecutive days). Myocardial perfusion defect area and coronary flow reserve (CFR) were compared during the 28-day follow-up. Also, serial changes in the absolute number of circulating CD4+T and CD8+T cells were measured. Results The increases in ejection fraction were significantly greater in both the SB and the DD groups compared to the placebo group (5.4-±-0.9%, 3.7-±-0.7%, and -0.4-±-0.6%, respectively), and the decrease in the perfusion defect area was significantly greater in the SB group than the placebo group (-36.3-±-1.8 and -11.5-±-2.8). CFR increased to a greater degree in the SB and the DD groups than in the placebo group (0.9-±-0.2, 0.8-±-0.1, and 0.2-±-0.2, respectively). The circulating number of CD8+T cells was significantly greater in the SB and DD groups than the placebo group at day 7 (3,687-±-317/μL, 3,454-±-787/μL, and 1,928-±-457/μL, respectively). The numbers of small vessels were significantly greater in the SB and the DD groups than the placebo group in the peri-infarct area. Conclusions Both intravenous SB and DD delivery of ASCs are effective modalities for the treatment of MI in swine. Intravenous delivery of ASCs, with its immunomodulatory and angiogenic effects, is an attractive noninvasive approach for myocardial rescue.

    Original languageEnglish (US)
    Pages (from-to)E38-E48
    JournalCatheterization and Cardiovascular Interventions
    Volume86
    Issue number2
    DOIs
    StatePublished - Aug 1 2015

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    Left Ventricular Function
    Swine
    Stem Cells
    Transplantation
    Myocardial Infarction
    Placebos
    Myocardial Ischemia
    Perfusion
    T-Lymphocytes
    Left Ventricular Dysfunction

    Keywords

    • adipose stem cell
    • intravenous injection
    • myocardial infarction
    • myocardial perfusion
    • ventricular dysfunction

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine
    • Radiology Nuclear Medicine and imaging

    Cite this

    Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model. / Jun Hong, Soon; Rogers, Pamela I.; Kihlken, John; Warfel, Jessica; Bull, Chris; Deuter-Reinhard, Maja; Feng, Dongni; Xie, Jie; Kyle, Aaron; Merfeld-Clauss, Stephanie; Johnstone, Brian H.; Traktuev, Dmitry O.; Chen, Peng Sheng; Lindner, Jonathan; March, Keith L.

    In: Catheterization and Cardiovascular Interventions, Vol. 86, No. 2, 01.08.2015, p. E38-E48.

    Research output: Contribution to journalArticle

    Jun Hong, S, Rogers, PI, Kihlken, J, Warfel, J, Bull, C, Deuter-Reinhard, M, Feng, D, Xie, J, Kyle, A, Merfeld-Clauss, S, Johnstone, BH, Traktuev, DO, Chen, PS, Lindner, J & March, KL 2015, 'Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model', Catheterization and Cardiovascular Interventions, vol. 86, no. 2, pp. E38-E48. https://doi.org/10.1002/ccd.25566
    Jun Hong, Soon ; Rogers, Pamela I. ; Kihlken, John ; Warfel, Jessica ; Bull, Chris ; Deuter-Reinhard, Maja ; Feng, Dongni ; Xie, Jie ; Kyle, Aaron ; Merfeld-Clauss, Stephanie ; Johnstone, Brian H. ; Traktuev, Dmitry O. ; Chen, Peng Sheng ; Lindner, Jonathan ; March, Keith L. / Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model. In: Catheterization and Cardiovascular Interventions. 2015 ; Vol. 86, No. 2. pp. E38-E48.
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    title = "Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model",
    abstract = "Objectives The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery. Methods Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n-=-7), the single bolus group (SB) (n-=-7, 15 × 107 ASCs), or the divided dose group (DD) (n-=-7, 5 × 107 ASCs/day for three consecutive days). Myocardial perfusion defect area and coronary flow reserve (CFR) were compared during the 28-day follow-up. Also, serial changes in the absolute number of circulating CD4+T and CD8+T cells were measured. Results The increases in ejection fraction were significantly greater in both the SB and the DD groups compared to the placebo group (5.4-±-0.9{\%}, 3.7-±-0.7{\%}, and -0.4-±-0.6{\%}, respectively), and the decrease in the perfusion defect area was significantly greater in the SB group than the placebo group (-36.3-±-1.8 and -11.5-±-2.8). CFR increased to a greater degree in the SB and the DD groups than in the placebo group (0.9-±-0.2, 0.8-±-0.1, and 0.2-±-0.2, respectively). The circulating number of CD8+T cells was significantly greater in the SB and DD groups than the placebo group at day 7 (3,687-±-317/μL, 3,454-±-787/μL, and 1,928-±-457/μL, respectively). The numbers of small vessels were significantly greater in the SB and the DD groups than the placebo group in the peri-infarct area. Conclusions Both intravenous SB and DD delivery of ASCs are effective modalities for the treatment of MI in swine. Intravenous delivery of ASCs, with its immunomodulatory and angiogenic effects, is an attractive noninvasive approach for myocardial rescue.",
    keywords = "adipose stem cell, intravenous injection, myocardial infarction, myocardial perfusion, ventricular dysfunction",
    author = "{Jun Hong}, Soon and Rogers, {Pamela I.} and John Kihlken and Jessica Warfel and Chris Bull and Maja Deuter-Reinhard and Dongni Feng and Jie Xie and Aaron Kyle and Stephanie Merfeld-Clauss and Johnstone, {Brian H.} and Traktuev, {Dmitry O.} and Chen, {Peng Sheng} and Jonathan Lindner and March, {Keith L.}",
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    TY - JOUR

    T1 - Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model

    AU - Jun Hong, Soon

    AU - Rogers, Pamela I.

    AU - Kihlken, John

    AU - Warfel, Jessica

    AU - Bull, Chris

    AU - Deuter-Reinhard, Maja

    AU - Feng, Dongni

    AU - Xie, Jie

    AU - Kyle, Aaron

    AU - Merfeld-Clauss, Stephanie

    AU - Johnstone, Brian H.

    AU - Traktuev, Dmitry O.

    AU - Chen, Peng Sheng

    AU - Lindner, Jonathan

    AU - March, Keith L.

    PY - 2015/8/1

    Y1 - 2015/8/1

    N2 - Objectives The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery. Methods Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n-=-7), the single bolus group (SB) (n-=-7, 15 × 107 ASCs), or the divided dose group (DD) (n-=-7, 5 × 107 ASCs/day for three consecutive days). Myocardial perfusion defect area and coronary flow reserve (CFR) were compared during the 28-day follow-up. Also, serial changes in the absolute number of circulating CD4+T and CD8+T cells were measured. Results The increases in ejection fraction were significantly greater in both the SB and the DD groups compared to the placebo group (5.4-±-0.9%, 3.7-±-0.7%, and -0.4-±-0.6%, respectively), and the decrease in the perfusion defect area was significantly greater in the SB group than the placebo group (-36.3-±-1.8 and -11.5-±-2.8). CFR increased to a greater degree in the SB and the DD groups than in the placebo group (0.9-±-0.2, 0.8-±-0.1, and 0.2-±-0.2, respectively). The circulating number of CD8+T cells was significantly greater in the SB and DD groups than the placebo group at day 7 (3,687-±-317/μL, 3,454-±-787/μL, and 1,928-±-457/μL, respectively). The numbers of small vessels were significantly greater in the SB and the DD groups than the placebo group in the peri-infarct area. Conclusions Both intravenous SB and DD delivery of ASCs are effective modalities for the treatment of MI in swine. Intravenous delivery of ASCs, with its immunomodulatory and angiogenic effects, is an attractive noninvasive approach for myocardial rescue.

    AB - Objectives The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery. Methods Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n-=-7), the single bolus group (SB) (n-=-7, 15 × 107 ASCs), or the divided dose group (DD) (n-=-7, 5 × 107 ASCs/day for three consecutive days). Myocardial perfusion defect area and coronary flow reserve (CFR) were compared during the 28-day follow-up. Also, serial changes in the absolute number of circulating CD4+T and CD8+T cells were measured. Results The increases in ejection fraction were significantly greater in both the SB and the DD groups compared to the placebo group (5.4-±-0.9%, 3.7-±-0.7%, and -0.4-±-0.6%, respectively), and the decrease in the perfusion defect area was significantly greater in the SB group than the placebo group (-36.3-±-1.8 and -11.5-±-2.8). CFR increased to a greater degree in the SB and the DD groups than in the placebo group (0.9-±-0.2, 0.8-±-0.1, and 0.2-±-0.2, respectively). The circulating number of CD8+T cells was significantly greater in the SB and DD groups than the placebo group at day 7 (3,687-±-317/μL, 3,454-±-787/μL, and 1,928-±-457/μL, respectively). The numbers of small vessels were significantly greater in the SB and the DD groups than the placebo group in the peri-infarct area. Conclusions Both intravenous SB and DD delivery of ASCs are effective modalities for the treatment of MI in swine. Intravenous delivery of ASCs, with its immunomodulatory and angiogenic effects, is an attractive noninvasive approach for myocardial rescue.

    KW - adipose stem cell

    KW - intravenous injection

    KW - myocardial infarction

    KW - myocardial perfusion

    KW - ventricular dysfunction

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