Intracoronary Infusion of Encapsulated Glucagon-Like Peptide-1–Eluting Mesenchymal Stem Cells Preserves Left Ventricular Function in a Porcine Model of Acute Myocardial Infarction

Mesenchymal stem cells (MSCs) from healthy donors improve cardiac function in experimental acute myocardial infarction (AMI) models. However, little is known about the therapeutic capacity of human MSCs (hMSCs) from patients with ischemic heart disease (IHD). Therefore, the behavior of hMSCs from IHD patients in an immune-compromised mouse AMI model was studied. Enhanced green fluorescent protein-labeled hMSCs from IHD patients (hMSC group: 2 × 105cells in 20 μl, n = 12) or vehicle only (medium group: n = 14) were injected into infarcted myocardium of NOD/ scid mice. Sham-operated mice were used as the control ( n = 10). Cardiac anatomy and function were serially assessed using 9.4-T magnetic resonance imaging (MRI); 2 wk after cell transplantation, immunohistological analysis was performed. At day 2, delayed-enhancement MRI showed no difference in myocardial infarction (MI) size between the hMSC and medium groups (33 ± 2% vs. 36 ± 2%; P = not significant). A comparable increase in left ventricular (LV) volume and decrease in ejection fraction (EF) was observed in both MI groups. However, at day 14, EF was higher in the hMSC than in the medium group (24 ± 3% vs. 16 ± 2%; P < 0.05). This was accompanied by increased vascularity and reduced thinning of the infarct scar. Engrafted hMSCs (4.1 ± 0.3% of injected cells) expressed von Willebrand factor (16.9 ± 2.7%) but no stringent cardiac or smooth muscle markers. hMSCs from patients with IHD engraft in infarcted mouse myocardium and preserve LV function 2 wk after AMI, potentially through an enhancement of scar vascularity and a reduction of wall thinning.

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Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction

European Heart Journal ◽

10.1093/eurheartj/ehm426 ◽

2007 ◽

Vol 28 (21) ◽

pp. 2667-2677 ◽

Cited By ~ 285

Author(s):

C. Valina ◽

K. Pinkernell ◽

Y.-H. Song ◽

X. Bai ◽

S. Sadat ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Stem Cells ◽

Adipose Tissue ◽

Left Ventricular Function ◽

Ventricular Function ◽

Left Ventricular ◽

Intracoronary Administration

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Transplantation of mesenchymal stem cells for prevention of acute myocardial infarction induced heart failure: Study protocol of a phase III randomized clinical trial

10.21203/rs.3.rs-915983/v1 ◽

2021 ◽

Author(s):

Armin Attar ◽

Ahmad Monabati ◽

Mohammad Montaseri ◽

Massoud Vosough ◽

Seyed Ali Hosseini ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Acute Myocardial Infarction ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Multicenter Trial ◽

Phase Iii ◽

Lv Function ◽

Bone Marrow Mononuclear Cell ◽

Intracoronary Infusion

Abstract Background: Results from recent clinical trials on bone marrow mononuclear cell (BM-MNC) transplantation show that this intervention can help reduce the incidence of heart failure (HF) after acute myocardial infarction (AMI). However, no study has evaluated the effect of the transplantation of mesenchymal stem cells (MSCs) on a clinical endpoint such as HF.Methods: This single-blinded, randomized, multicenter trial aims to establish whether the intracoronary infusion of umbilical cord-derived Wharton’s jelly MSCs (WJ-MSCs) helps prevent HF development after AMI. The study will enroll 360 patients 3 to 7 days following AMI. Only patients aged below 65 years with impaired LV function (LVEF < 40%) will be included. They will be randomized (2:1 ratio) to either receive standard care or a single intracoronary infusion of 107 WJ-MSCs. The primary outcome of this study is the assessment of HF development during long-term follow-up (3 years).Results: Data will be collected until Nov 2024. Thereafter, the analysis will be conducted. Results are expected to be ready by Dec 2024. We will prepare and submit the related manuscript in accordance with the SPIRIT guidelines. Conclusions: This study will help determine whether or not the infusion of intracoronary WJ-MSCs in patients with AMI will reduce the incidence of AMI-induced HF.Trial Registration: ClinicalTrials.gov, NCT05043610, Registered 14 September 2021 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05043610

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Bone Marrow Stem Cells Infusion in Treatment of Patients with Acute Myocardial Infarction.

Blood ◽

10.1182/blood.v108.11.1682.1682 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1682-1682

Author(s):

Lidia Gil ◽

Anna Czyz ◽

Krzysztof Sawinski ◽

Maria Kozlowska-Skrzypczak ◽

Mieczyslaw Komarnicki ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Stem Cells ◽

Bone Marrow ◽

Left Ventricular Function ◽

Ventricular Function ◽

Left Ventricular ◽

Control Group ◽

Acute Pulmonary Oedema ◽

Autologous Plasma

Abstract Experimental and clinical data show that bone marrow-derived stem cells (BMSC) can contribute to myocardial regeneration after ischemic injury. We present results of intracoronary infusion of autologous BMSCs in treatment of patients (pts) with acute myocardial infarction (MI). 36 pts with first, anterior wall MI, successfully treated with percutaneous coronary angioplasty were enrolled into the study. 24 pts, aged 50.1±9.05 yrs received intracoronary BMSC infusion 4 to 7 days after MI. Control group consisted of 12 pts, aged 51.6±8.7 yrs. In BMSC group BM in total volume 80 (50–150) ml was collected from iliac crest to buffered saline with heparine. After isolation and 18–24 hrs cultivation BMSCs were resuspended in autologous plasma in final volume 12.25±2.05 ml. The mean number of MNC, CD34+, CD133+/CD45+ and CD133+/CD45− cells were respectively: 0.41±0.18x10e9, 3.89±1.45x10e6, 0.96±0.6x10e6, 0.15±0.1x10e6. Transplanted material was divided into 3–5 portion and injected directly to infarcted area (Strauer method). Left ventricular function was evaluated by echocardiography (contactility index, CI), Tc-99 MIBI SPECT (perfusion index, PI) at rest (R) and with dipiridamol (D) and radionuclide ventriculography (ejection fraction, EF) at baseline and after 3, 6, 12 months (mo). CI and PI were assessed in left ventricle and infarct related artery (IRA) area. Control coronary angiography was performed after 6 mo. No adverse effects of BM aspiration in early MI were observed. One pts revealed chills and fever and 1 acute pulmonary oedema after cell infusion. Control angiography revealed restenosis in 3 pts from BMSC and 2 from control group. Results of cardiac test are presented in table. Conclusions: Intracoronary autologous BMNCs transplantation is safe and feasible. Improvement of left ventricular function was observed in BMSC group, mainly concerning perfusion. No accelerated atherosclerosis was seen after intracoronary BMSC administration. Results of cardiac tests BMSC group Control group p CI/CI-IRA 7 day 1.62±0.19/2.3±0.36 1.6±0.24/2.21±0.41 ns CI/CI-IRA 3 mo 1.55±0.2/2.12±0.4 1.65±0.3/2.34±0.64 ns CI/CI-IRA 6 mo 1.5±0.2/2.16±0.37 1.7±0.29/2.46±0.51 0.02 CI/CI-IRA 12 mo 1.55±0.2/2.24±0.44 1.72±0.33/2.48±0.51 ns Pi/PI-IRA-R 10 day 2.45±0.63/2.96±0.88 2.45±0.53/3.04±0.74 ns PI/PI-IRA-R 3 mo 2.25±0.37/2.79±0.61 2.36±0.44/2.88±0.61 ns PI/PI-IRA-R 6 mo 2.19±0.43/2.68±0.67 2.43±0.32/3.02±0.45 0.07 PI/PI-IRA-R 12 mo 2.11±0.33/2.63±0.46 2.36±0.31/2.98±0.46 ns PI/PI-IRA-D 10 day 2.45±0.63/2.96±0.88 2.45±0.53/3.04±0.74 ns PI/PI-IRA-D 3 mo 2.3±0.42/2.87±0.67 2.43±0.4/2.93±0.44 ns PI/PI-IRA-D 6 mo 2.2±0.44/2.58±0.83 2.48±0.43/3.12±0.48 0.06 PI/PI-IRA-D 12 mo 2.16±0.43/2.59±0.6 2.57±0.44/3.35±0.42 0.009 EF 4 day 45.0±7.9 41.6±6.6 ns EF 6 mo 48.2±9.2 42.1±11.4 0.07 EF 12 mo 48.5±4.9 38.9±7.7 0.002

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