Premium
Intravenous xenogeneic transplantation of human adipose‐derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model
Author(s) -
Hong Soon Jun,
Rogers Pamela I.,
Kihlken John,
Warfel Jessica,
Bull Chris,
DeuterReinhard Maja,
Feng Dongni,
Xie Jie,
Kyle Aaron,
MerfeldClauss Stephanie,
Johnstone Brian H.,
Traktuev Dmitry O.,
Chen PengSheng,
Lindner Jonathan R.,
March Keith L.
Publication year - 2015
Publication title -
catheterization and cardiovascular interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.988
H-Index - 116
eISSN - 1522-726X
pISSN - 1522-1946
DOI - 10.1002/ccd.25566
Subject(s) - medicine , perfusion , placebo , ejection fraction , myocardial infarction , adipose tissue , cardiology , transplantation , bolus (digestion) , coronary flow reserve , stem cell , urology , blood flow , pathology , heart failure , alternative medicine , biology , genetics
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 × 10 7 ASCs), or the divided dose group (DD) ( n = 7, 5 × 10 7 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. © 2014 Wiley Periodicals, Inc.