Cardiac function evaluation of bone marrow mesenchymal stromal cells intracoronary transplantation in acute myocardial infarction Lee-Sung mini-PIG model

Background & Aim Acute myocardial infarction (AMI) is the single most common cause of death worldwide. Mesenchymal stromal cells (MSC) exert strong immunomodulatory effects and angiogenesis property. MSC cell therapy in AMI therefore showed some beneficial effects in several studies and clinical trials. Here we isolated, expanded and characterized human bone marrow MSC in serum free condition under GTP regulation and evaluated the efficacy of these MSC in porcine AMI model after intracoronary injection. Methods, Results & Conclusion These MSC also showed strong immunosuppression, T cell suppression, immunomodulation and anti-inflammatory activity by MLR, T cell proliferation, IDO activity and INF-r TNF-a expression assay. AMI was induced in Lee-Sung mini pigs by inflating an angioplasty balloon for 90 mins in the mid-left anterior descending artery. After reperfusion for 90min, MSC or buffer were intracoronary injected through the central lumen of the balloon catheter. Fifteen animals were randomly divided into three groups: shame control; AMI-M (MSCs injection); AMI-B (Buffer injection). After 90 min balloon occlusion, the left ventricular ejection fraction (LVEF) by echocardiography of three groups were reduced from 62.94±4.28% (sham), 62.46±2.10% (AMI-B), 61.01±3.21% (AMI-M) to 63.08±5.69 % (sham), 37.44±4.27% (AMI-B), 39.92±2.67% (AMI-M), respectively. ST-segment elevation were observed by electrocardiography. Three months after AMI, LEVF of sham group was 60.98±3.82 %. LVEF of AMI-B group remained low at 36.68±3.12 % while AMI-M group rose to 53.71±4.46 %. The concentration of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) of three groups were 4.6, 19.5 pg/mL (sham); 149.2, 388.6 pg/mL (AMI-B) and 21.9, 46.1 pg/mL (AMI-M) after 24 hours of AMI, respectively. Those biomarker of AMI-B was higher than ULRF while AMI-M group was reduced to lower than the MI reference value. It suggested that the MSC transplantation may suppress the myocardial necrosis caused by AMI. LEVF and MRI images as well as blood concentration of cTnT I/T were analyzed during five-month follow-up. After 5 months of observation, the status of tissue necrosis, fibrosis or angiogenesis were assayed by tissue analysis including TCC staining; hematoxylin-eosin staining; Masson Trichrome staining; immunohistochemistry staining with cTnT, cTnI, vWF and isolectin-B4. In conclusion, our bone marrow MSCs showed promising potential for cardiac function improvement after intracoronary transplantation into AMI Lee-Sung mini-pig.