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HEART FAILURE AFFECTS BONE MARROW MESENCHYMAL STEM RENEWING CAPACITY
1451 JACC April 5, 2016 Volume 67, Issue 13
Heart Failure and Cardiomyopathies HEART FAILURE AFFECTS BONE MARROW MESENCHYMAL STEM RENEWING CAPACITY Poster Contributions Poster Area, South Hall A1 Sunday, April 03, 2016, 9:45 a.m.-10:30 a.m. Session Title: Heart Failure and Cardiomyopathies: Transplantation/Stem Cells/Catheter Based Therapies Abstract Category: 27. Heart Failure and Cardiomyopathies: Therapy Presentation Number: 1172-083 Authors: Cristina Sanina, Victoria Florea, Darcy Difede, Krystalenia Valasaki, Aisha Khan, Joshua Hare, Stem Cell Institute University of Miami, Miami, FL, USA
Background: Clinical trials have shown a sustained beneficial effect of bone marrow mesenchymal stem cells (MSCs) as a therapy for acute and chronic heart failure (HF). Clinical grade cell manufacturing of autologous and allogeneic bone-marrow derived MSCs is becoming a standard procedure. This study investigates the differences of bone marrow MSC isolation and expansion in favorable in vitro conditions. We compared MSC production from both healthy young donors and chronic HF patients.
Methods: We analyzed MSC manufacturing records from five clinical trials: TAC-HFT (Ischemic cardiomyopathy, patient-donors), POSEIDON (Ischemic cardiomyopathy, patient- vs healthy donors), POSEIDON DCM (Dilated cardiomyopathy, patient- vs healthy donors), TRIDENT (Ischemic cardiomyopathy, healthy donors), and CRATUS (Frailty, healthy donors). Results: All cells expressed CD105 and lacked hematopoietic marker CD45.The age of healthy donors (25.50 ± 0.69 y.o., N=24) and heart failure patients (56.09 ± 2.544, y.o., N=23), was significantly different (P<0.0001). Collectively, the number of mononuclear cells (MNCs) isolated from bone marrow (volume range 58-125 ml) didn’t differ between the groups. However, plated MNCs from healthy young adults generated more MSCs than MNCs from HF patients (p0: 5.98x10^6±0.5x10^6, N=23 vs 3.82x10^6±0.4x10^6, N=24, respectively, P=0.003 and p1: 15.4x10^6±2.5x10^6, N=23 vs 10.8x10^6±1.1x10^6, N=24, respectively, P=0.036). No correlation was found between stem cell growth, age (35 to 78 y.o.) and the presence of diabetes mellitus (DM) in patient group. Left ventricular ejection fraction (LVEF) in patients with HF had a direct correlation with MSC growth rate (P=0.03), particularly, in patients with severely depressed LVEF (<30%), which had a tendency to generate less MSCs overall.
Conclusions: Despite equivalent numbers of MNCs, healthy young donors generate significantly more MSCs than HF patients, due to increased growth rate and higher number of resident stromal bone marrow stem cells. Heart failure appears to be an independent factor for MSC renewal capacity and culture phenotype.
Heart Failure and Cardiomyopathies HEART FAILURE AFFECTS BONE MARROW MESENCHYMAL STEM RENEWING CAPACITY Poster Contributions Poster Area, South Hall A1 Sunday, April 03, 2016, 9:45 a.m.-10:30 a.m. Session Title: Heart Failure and Cardiomyopathies: Transplantation/Stem Cells/Catheter Based Therapies Abstract Category: 27. Heart Failure and Cardiomyopathies: Therapy Presentation Number: 1172-083 Authors: Cristina Sanina, Victoria Florea, Darcy Difede, Krystalenia Valasaki, Aisha Khan, Joshua Hare, Stem Cell Institute University of Miami, Miami, FL, USA
Background: Clinical trials have shown a sustained beneficial effect of bone marrow mesenchymal stem cells (MSCs) as a therapy for acute and chronic heart failure (HF). Clinical grade cell manufacturing of autologous and allogeneic bone-marrow derived MSCs is becoming a standard procedure. This study investigates the differences of bone marrow MSC isolation and expansion in favorable in vitro conditions. We compared MSC production from both healthy young donors and chronic HF patients.
Methods: We analyzed MSC manufacturing records from five clinical trials: TAC-HFT (Ischemic cardiomyopathy, patient-donors), POSEIDON (Ischemic cardiomyopathy, patient- vs healthy donors), POSEIDON DCM (Dilated cardiomyopathy, patient- vs healthy donors), TRIDENT (Ischemic cardiomyopathy, healthy donors), and CRATUS (Frailty, healthy donors). Results: All cells expressed CD105 and lacked hematopoietic marker CD45.The age of healthy donors (25.50 ± 0.69 y.o., N=24) and heart failure patients (56.09 ± 2.544, y.o., N=23), was significantly different (P<0.0001). Collectively, the number of mononuclear cells (MNCs) isolated from bone marrow (volume range 58-125 ml) didn’t differ between the groups. However, plated MNCs from healthy young adults generated more MSCs than MNCs from HF patients (p0: 5.98x10^6±0.5x10^6, N=23 vs 3.82x10^6±0.4x10^6, N=24, respectively, P=0.003 and p1: 15.4x10^6±2.5x10^6, N=23 vs 10.8x10^6±1.1x10^6, N=24, respectively, P=0.036). No correlation was found between stem cell growth, age (35 to 78 y.o.) and the presence of diabetes mellitus (DM) in patient group. Left ventricular ejection fraction (LVEF) in patients with HF had a direct correlation with MSC growth rate (P=0.03), particularly, in patients with severely depressed LVEF (<30%), which had a tendency to generate less MSCs overall.
Conclusions: Despite equivalent numbers of MNCs, healthy young donors generate significantly more MSCs than HF patients, due to increased growth rate and higher number of resident stromal bone marrow stem cells. Heart failure appears to be an independent factor for MSC renewal capacity and culture phenotype.