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 R. Lindner, Keith L. March

Research output: Contribution to journalArticle

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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
Pages (from-to)E38-E48
JournalCatheterization and Cardiovascular Interventions
Volume86
Issue number2
DOIs
Publication statusPublished - 2015 Aug 1

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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

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model. / Hong, Soon Jun; 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 R.; March, Keith L.

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

Research output: Contribution to journalArticle

Hong, SJ, 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, JR & 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
Hong, Soon Jun ; 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 R. ; 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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AU - Hong, Soon Jun

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 R.

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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