title: Substantial early loss of induced pluripotent stem cells following transplantation in myocardial infarction.
abstract: The limited success of cardiac stem cell therapy has lately generated discussion regarding its effectiveness. We hypothesized that immediate cell loss after intramyocardial injection significantly obscures the regenerative potential of stem cell therapy. Therefore, our aim was to assess the distribution and quantity of induced pluripotent stem cells after intramyocardial delivery using in vivo bioluminescence analysis. In this context, we wanted to investigate if the injection of different cell concentrations would exert influence on cardiac cell retention. Murine-induced pluripotent stem cells were transfected for luciferase reporter gene expression and transplanted into infarcted myocardium in mice after left anterior descending coronary artery ligation. Cells were delivered constantly in aqueous media (15 μL) in different cell concentrations (group A, n = 10, 5.0 × 10(5) cells; group B, n = 10, 1.0 × 10(6) cells). Grafts were detected using bioluminescence imaging. Organ explants were imaged 10 min after injection to quantify early cardiac retention and cell biodistribution. Bioluminescence imaging showed a massive early displacement from the injection site to the pulmonary circulation, leading to lung accumulation. Mean cell counts of explanted organs in group A were 7.51 × 10(4) ± 4.09 × 10(3) (heart), 6.44 × 10(4) ± 2.48 × 10(3) (left lung), and 8.06 × 10(5) ± 3.61 × 10(3) (right lung). Respective cell counts in group B explants were 1.69 × 10(5) ± 7.69 × 10(4) (heart), 2.11 × 10(5) ± 4.58 × 10(3) (left lung), and 3.25 × 10(5) ± 9.35 × 10(3) (right lung). Applying bioluminescence imaging, we could unveil and quantify massive early cardiac stem cell loss and pulmonary cell accumulation following intramyocardial injection. Increased injection concentrations led to much higher intracardiac cell counts; however, pulmonary biodistribution of transplanted cells still persisted. Therefore, we recommend applying tissue engineering techniques for cardiac stem cell transplantations in order to improve cardiac retention and limit biodistribution.
authors.affiliation: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Martens
authors.forename: Sebastian V
authors.initials: SV
authors.lastname: Rojas
authors.forename: Hassina
authors.initials: H
authors.lastname: Baraki
authors.forename: Christian
authors.initials: C
authors.lastname: Rathert
authors.forename: Natalie
authors.initials: N
authors.lastname: Schecker
authors.forename: Robert
authors.initials: R
authors.lastname: Zweigerdt
authors.forename: Kristin
authors.initials: K
authors.lastname: Schwanke
authors.forename: Sara
authors.initials: S
authors.lastname: Rojas-Hernandez
authors.forename: Ulrich
authors.initials: U
authors.lastname: Martin
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Saito
authors.forename: Jan D
authors.initials: JD
authors.lastname: Schmitto
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Ingo
authors.initials: I
authors.lastname: Kutschka
mesh_terms: D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D015552:Injections, Intralesional; D008163:Luminescent Measurements; D051379:Mice; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000628:therapy*
keywords: Induced pluripotent stem cells; Injection loss; Myocardial infarction; Stem cell therapy