Administration of Cardiac Stem Cells in Patients With Ischemic Cardiomyopathy: The SCIPIO Trial

Abstract

Background SCIPIO is a first-in-human, phase 1, randomized, open-label trial of autologous c-kit+ cardiac stem cells (CSCs) in patients with heart failure of ischemic etiology undergoing coronary artery bypass grafting (CABG). Here, we report the surgical aspects and interim cardiac magnetic resonance (CMR) results. Methods and Results A total of 33 patients (20 CSC-treated and 13 controls) met final eligibility criteria and were enrolled in SCIPIO. CSCs were isolated from the right atrial appendage harvested and processed during surgery. Harvesting did not affect cardiopulmonary bypass, cross-clamp, or surgical times. In CSC-treated patients, CMR showed a marked increase in both LVEF (from 27.5 ± 1.6% to 35.1 ± 2.4 % [P=0.004, n=8] and 41.2 ± 4.5 % [P=0.013, n=5] at 4 and 12 months after CSC infusion, respectively) and regional EF in the CSC-infused territory. Infarct size (late gadolinium enhancement) decreased after CSC infusion (by manual delineation: -6.9 ± 1.5 g [-22.7%] at 4 months [P=0.002, n=9] and -9.8 ± 3.5 g [-30.2%] at 12 months [P=0.039, n=6],). LV non-viable mass decreased even more (-11.9 ± 2.5 g [-49.7%] at 4 months [P=0.001] and -14.7 ± 3.9 g [-58.6%] at 12 months [P=0.013]), while LV viable mass increased (+11.6 ± 5.1 g at 4 months after CSC infusion [P=0.055] and +31.5 ± 11.0 g at 12 months [P=0.035]). Conclusions Isolation of CSCs from cardiac tissue obtained in the operating room is feasible and does not alter practices during CABG surgery. CMR shows that CSC infusion produces a striking improvement in both global and regional LV function, a reduction in infarct size, and an increase in viable tissue, which persist at least 1 year and are consistent with cardiac regeneration. Clinical Trial Registration This study is registered with clinicaltrials.gov, trial number NCT00474461.

Comparative study of immune regulatory properties of stem cells derived from different tissues

“…To test this hypothesis, we studied (1) BM-MSCs [25]; (2) olfactory ectomesenchymal SCs (OEMSCs), which are distributed in the olfactory lamina propria and induce neurogenesis, and restore the hippocampal neuronal network [44][45][46]; (3) non-MSC leptomeningeal SCs (LeSCs), described by us first in rats as nestin-positive cells capable of differentiating into neuronal, astrocyte, and oligodendrocyte precursors [47,48] and, more recently, in mice and humans (personal observation); and (4) human c-Kitpositive SCs isolated from the amniotic fluid (AFSCs) [49], from the adult heart (cardiac SCs: CSCs) [50][51][52]; and adult lung SCs (LSCs) [53]. AFSCs are multipotent, nonteratogenic cells with characteristics intermediate between embryonic and adult SCs [49].…”

“…AFSCs are multipotent, nonteratogenic cells with characteristics intermediate between embryonic and adult SCs [49]. CSCs are multipotent cells capable of differentiating into cardiomyocytes and coronary vessels [50][51][52], while LSCs form lung structures of both endodermal and mesodermal origin [53]. The standardized approach previously introduced to characterize MSCs [25] was applied to all SCs to define their immunological profile.…”

Engineering Cardiovascular Regeneration

“…MSC are still being investigated for their capacity to regenerate cardiomyocytes [23], but the evidence remains controversial [24]. The capacity of c-kitpositive resident stem cells [25] to form new myocytes under normal and diseased conditions has been seriously challenged by a carefully conducted study using genetic targeting of the ckit locus [26]. A clinical study with these cells, originally published in The Lancet [27], raised concerns [28].…”

A Holistic Approach to Managing a Patient With Heart Failure

“…Pfeffer described the years of 'bench-to-bedside' research that culminate in changing clinical practice, such as the SAVE trial (captopril following myocardial infarction) [8]. Finally, Pfeffer explored the future of cardiac remodeling, in particular, the role of stem cell therapy in HF patients [9].…”