Effects of Intracoronary Administration of Autologous Adipose Tissue-Derived Stem Cells on Acute Myocardial Infarction in a Porcine Model

Lee, Hye Won; Lee, Han Cheol; Park, Jong Ha; Kim, Bo Won; Ahn, Jinhee; Kim, Jin Hee; Park, Jin Sup; Oh, Jun-Hyok; Choi, Jung Hyun; Soo, Kwang; Hong, Taek Jong; Park, Tae Sik; Kim, Sang-Pil; Song, Seunghwan; Kim, Ji Yeon; Park, Mi Hwa; Jung, Jin Sup

doi:10.3349/ymj.2015.56.6.1522

Cited by 28 publications

(20 citation statements)

References 27 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although MVO persists at least 1 week after reperfusion, our study found no MVO increase at 7 days post‐AMI in those animals receiving 10 7 ATMSCs (≈13 μm in diameter) in the LAD just after reperfusion. Our finding agrees with most of the previous literature and supports the feasibility and safety of intracoronary administration of large‐size cells just after reperfusion as long as precautions are taken in determining the infusion rate and dose.…”

Section: Discussionsupporting

confidence: 92%

“…Intracoronary administration is one of the least invasive delivery methods, although infusion of large‐size adult mesenchymal stem cells (MSCs) (up to 20 μm in diameter) could potentially obstruct capillaries (from 6 to 10 μm in diameter), leading to permanent no‐reflow phenomena after cell administration. In this sense, clinical and preclinical studies have found that intracoronary injection of a significant number (up to 50 million) of large‐size stem cells (≈20–50 μm in diameter) can be safe when administered a few days after AMI. However, microvascular injury is higher during the first 24 hours post‐AMI, and therefore the probability of capillary plugging and MVO increases when administering large cells directly into the culprit artery.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Intracoronary Administration of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells Improves Myocardial Perfusion But Not Left Ventricle Function, in a Translational Model of Acute Myocardial Infarction

Bobi

Solanes

Fernández‐Jiménez

et al. 2017

JAHA

View full text Add to dashboard Cite

BackgroundAutologous adipose tissue–derived mesenchymal stem cells (ATMSCs) therapy is a promising strategy to improve post–myocardial infarction outcomes. In a porcine model of acute myocardial infarction, we studied the long‐term effects and the mechanisms involved in allogeneic ATMSCs administration on myocardial performance.Methods and ResultsThirty‐eight pigs underwent 50 minutes of coronary occlusion; the study was completed in 33 pigs. After reperfusion, allogeneic ATMSCs or culture medium (vehicle) were intracoronarily administered. Follow‐ups were performed at short (2 days after acute myocardial infarction vehicle‐treated, n=10; ATMSCs‐treated, n=9) or long term (60 days after acute myocardial infarction vehicle‐treated, n=7; ATMSCs‐treated, n=7). At short term, infarcted myocardium analysis showed reduced apoptosis in the ATMSCs‐treated animals (48.6±6% versus 55.9±5.7% in vehicle; P=0.017); enhancement of the reparative process with up‐regulated vascular endothelial growth factor, granulocyte macrophage colony‐stimulating factor, and stromal‐derived factor‐1α gene expression; and increased M2 macrophages (67.2±10% versus 54.7±10.2% in vehicle; P=0.016). In long‐term groups, increase in myocardial perfusion at the anterior infarct border was observed both on day‐7 and day‐60 cardiac magnetic resonance studies in ATMSCs‐treated animals, compared to vehicle (87.9±28.7 versus 57.4±17.7 mL/min per gram at 7 days; P=0.034 and 99±22.6 versus 43.3±14.7 22.6 mL/min per gram at 60 days; P=0.0001, respectively). At day 60, higher vascular density was detected at the border zone in the ATMSCs‐treated animals (118±18 versus 92.4±24.3 vessels/mm2 in vehicle; P=0.045). Cardiac magnetic resonance–measured left ventricular ejection fraction of left ventricular volumes was not different between groups at any time point.ConclusionsIn this porcine acute myocardial infarction model, allogeneic ATMSCs‐based therapy was associated with increased cardioprotective and reparative mechanisms and with better cardiac magnetic resonance–measured perfusion. No effect on left ventricular volumes or ejection fraction was observed.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Intracoronary Administration of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells Improves Myocardial Perfusion But Not Left Ventricle Function, in a Translational Model of Acute Myocardial Infarction

Bobi

Solanes

Fernández‐Jiménez

et al. 2017

JAHA

View full text Add to dashboard Cite

show abstract

“…In addition to these advantages, many studies have used ADSCs for cell therapies and tissue engineering due to their ease of obtainment and varied applications. However, transplanted ADSCs survive poorly in the inflammatory and ischaemic microenvironment of acute myocardial infarction [4, 5]. To increase the survival of the transplanted cells, genetically engineered methods have been used [6, 7], but ethical and safety challenges remain.…”

Section: Introductionmentioning

confidence: 99%

Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury

Luo¹,

Guo²,

Liu³

et al. 2017

Cell Physiol Biochem

216

158

View full text Add to dashboard Cite

Background/Aims: Recent studies have indicated that exosomes play an important role in adipose-derived stem cell (ADSC) transplant-mediated ischaemic heart disease therapy. However, the treatment effect is not obvious. The aim of this study is to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-126 have a more protective effect on acute myocardial infarction (AMI). Methods: Exosomes were characterized by transmission electron microscopy, and the exosome particles were further examined using nanoparticle tracking analyses. A rat model of myocardial infarction and in vitro model of hypoxia-induced H9c2 myocardial cell injury were established to study the protective mechanism of exosomes from miR-126-overexpressing ADSCs. Results: The in vitro results showed that exosomes derived from miR-126-overexpressing ADSCs decreased H9c2 myocardial cell injury by reducing inflammation factor expression during hypoxia induction. The miR-126-enriched exosomes also decreased the expression of fibrosis-related proteins of H9c2 cells under hypoxic conditions. Matrigel® and Transwell® assays showed that miR-126-enriched exosomes significantly promoted microvascular generation and migration, respectively. In vivo studies confirmed that exosomes derived from ADSCs significantly decreased the myocardial injury area of infarction, especially after miR-126-enriched exosome treatment. Cardiac fibrosis and inflammatory cytokine expression were also decreased after treatment with miR-126-enriched exosomes. However, blood vessel formation was promoted in the infarction region of AMI rats. Conclusions: The results suggested that the expression of miR-126-enhanced ADSC-derived exosomes prevented myocardial damage by protecting myocardial cells from apoptosis, inflammation, fibrosis, and increased angiogenesis.

show abstract

“…While the safety of both autologous and allogeneic MSCs is reasonably well established, studies have demonstrated that allogeneic MSCs derived from young, healthy donors are more efficacious 1, 5, 6. Notably, these cells are shown to be a safe method to improve cardiac structure and function in preclinical and clinical trials 1, 2, 7, 8, 9, 10, 11, 12. The question remains: In which pathologic setting are MSCs most effective?…”

Section: Introductionmentioning

confidence: 99%

Comparison of Mesenchymal Stem Cell Efficacy in Ischemic Versus Nonischemic Dilated Cardiomyopathy

Tompkins

Rieger²,

Florea³

et al. 2018

JAHA

View full text Add to dashboard Cite

BackgroundIschemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) differ in histopathology and prognosis. Although transendocardial delivery of mesenchymal stem cells is safe and provides cardiovascular benefits in both, a comparison of mesenchymal stem cell efficacy in ICM versus DCM has not been done.Methods and ResultsWe conducted a subanalysis of 3 single‐center, randomized, and blinded clinical trials: (1) TAC‐HFT (Transendocardial Autologous Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells in Ischemic Heart Failure Trial); (2) POSEIDON (A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction); and (3) POSEIDON‐DCM (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy). Baseline and 1‐year cardiac structure and function and quality‐of‐life data were compared in a post hoc pooled analysis including ICM (n=46) and DCM (n=33) patients who received autologous or allogeneic mesenchymal stem cells. Ejection fraction improved in DCM by 7% (within‐group, P=0.002) compared to ICM (1.5%; within‐group, P=0.14; between‐group, P=0.003). Similarly, stroke volume increased in DCM by 10.59 mL (P=0.046) versus ICM (−0.2 mL; P=0.73; between‐group, P=0.02). End‐diastolic volume improved only in ICM (10.6 mL; P=0.04) and end‐systolic volume improved only in DCM (17.8 mL; P=0.049). The sphericity index decreased only in ICM (−0.04; P=0.0002). End‐diastolic mass increased in ICM (23.1 g; P<0.0001) versus DCM (−4.1 g; P=0.34; between‐group, P=0.007). The 6‐minute walk test improved in DCM (31.1 m; P=0.009) and ICM (36.3 m; P=0.006) with no between‐group difference (P=0.79). The New York Heart Association class improved in DCM (P=0.005) and ICM (P=0.02; between‐group P=0.20). The Minnesota Living with Heart Failure Questionnaire improved in DCM (−19.5; P=0.002) and ICM (−6.4; P=0.03; δ between‐group difference P=0.042) patients.ConclusionsMesenchymal stem cell therapy is beneficial in DCM and ICM patients, despite variable effects on cardiac phenotypic outcomes. Whereas cardiac function improved preferentially in DCM patients, ICM patients experienced reverse remodeling. Mesenchymal stem cell therapy enhanced quality of life and functional capacity in both etiologies.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifiers: TAC‐HFT: NCT00768066, POSEIDON: NCT01087996, POSEIDON‐DCM: NCT01392625.

show abstract

Effects of Intracoronary Administration of Autologous Adipose Tissue-Derived Stem Cells on Acute Myocardial Infarction in a Porcine Model

Cited by 28 publications

References 27 publications

Intracoronary Administration of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells Improves Myocardial Perfusion But Not Left Ventricle Function, in a Translational Model of Acute Myocardial Infarction

Intracoronary Administration of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells Improves Myocardial Perfusion But Not Left Ventricle Function, in a Translational Model of Acute Myocardial Infarction

Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury

Comparison of Mesenchymal Stem Cell Efficacy in Ischemic Versus Nonischemic Dilated Cardiomyopathy

Contact Info

Product

Resources

About