P774Transcoronary transfer of Wharton's jelly mesenchymal pluripotent stem cells in patients with chronic ischaemic heart failure shows safety and unprecedented high-grade myocardial uptake

Abstract

Background Chronic ischaemic heart failure (CIHF) remains an important health problem on the patient/family- and society level. In animal models, Wharton's jelly (umbilical cord matrix) multipotent stem cells (WJMSCs) effectively promote angiogenesis, can differentiate to cardiomyocytes, and drive functional myocardial regeneration. Effective uptake of regenerative cells in ischaemic-impaired tissue is fundamental for any therapeutic effect. Purpose To evaluate safety and myocardial uptake of WJMSCs transcoronary transfer in CIHF applied as a novel myocardial regeneration strategy employing allogenic yet hypo-immunogenic, off-the-shelf “unlimited” source of therapeutic cells (NCT03418233 pilot cohort). Material and methods In ten consecutive patients (age 62.6±2.5), with stable CIHF and no current need for revascularization (LVEF 29.3±3% by echo and 26.3±6% by SPECT; NT-proBNP 1746±329pg/mL; myocardial scar tissue 39.9±3.9% by SPECT) and patency of at least two major native coronary arteries or by-pass graft(s), the CardioCell Investigational Medical Product, based on 30x106 WJMSCs, was administered to viable yet hypokinetic segments using a novel algorithm including a dedicated catheter for transcoronary delivery of cellular therapies. The cells were labeled with 99mTc-extametazime to routinely evaluate their myocardial uptake magnitude. Results No symptoms or signs of novel myocardial ischaemia occurred with cell delivery and no patient showed any adverse periprocedural events. One hour after administration, myocardial WJMSCs uptake (SPECT) was 40.3±6%; see Fig for a typical raw data image. By 6 months there were no adverse events in the study cohort. Figure 1 Conclusions This work indicates safety and unprecedented high-grade myocardial uptake of WJMSCs in CIHF patients. Together with animal data, this provides basis for continued assessment of this strategy in an endpoint-powered randomized controlled clinical trial employing CardioCell as an “unlimited” off-the-shelf cellular therapy strategy. Acknowledgement/Funding K/ZDS/005644 and 265761 (National Centre for Research and Development STRATEGMED)

Trans-endocardial delivery of progenitor cells to compromised myocardium using the “needle technique”and risk of myocardial injury

“…We assume that MSC, despite their regenerative potential, immunoregulatory properties, and ability to improve myocardial perfusion and left ventricular function [1,18], may not fully compensate for periprocedural damage caused by endomyocardial delivery, as we observed a residual increase in WMSI on day 30 after the procedure.…”

“…Our findings demonstrate that in patients with iCHF, endomyocardial delivery of mesenchymal stem cells is associated with transient regional left ventricular systolic dysfunction observed the day after the procedure and its gradual, though not complete, resolution within 30 days. Taken together with other limitations of the transendocardial “needle-based” approach (including the ‘geographic’ limitations related to the anatomy of the endocardial surface of the myocardium and the very focal nature of therapeutic agent delivery), transcoronary delivery techniques might be preferable once the terapeutic cells uptake is confirmed with labeling techniques [ 25 ].…”

Single-photon emission computed tomography as a fundamental tool in evaluation of myocardial reparation and regeneration therapies

“…The results of numerous important studies in humans confirm observations from animal model concerning cell retention and distribution. Table III provides the most relevant data from studies in humans in which SPECT was used [29,34,[62][63][64][65][66][67][68][69][70][71].…”