Autologous Umbilical Cord Blood Mononuclear Cell Transplantation Preserves Right Ventricular Function in a Novel Model of Chronic Right Ventricular Volume Overload

Abstract

We aimed to evaluate the feasibility and efficacy of autologous umbilical cord blood mononuclear cell (UCMNC) transplantation on right ventricular (RV) function in a novel model of chronic RV volume overload. Four-month-old sheep (n = 20) were randomized into cell (n = 10) and control groups (n = 10). After assessment of baseline RV function by the conductance catheter method, a transannular patch (TAP) was sutured to the right ventricular outflow tract (RVOT). Following infundibulotomy the ring of the pulmonary valve was transected without cardiopulmonary bypass. UCMNC implantation (8.22 +/- 6.28 x 10(7)) in the cell group and medium injection in the control group were performed into the RV myocardium around the TAP. UCMNCs were cultured for 2 weeks after fluorescence-activated cell sorting (FACS) analysis for CD34 antigen. Transthoracic echocardiography (TTE) and computed tomography were performed after 6 weeks and 3 months, respectively. RV function was assessed 3 months postoperatively before the hearts were excised for immunohistological examinations. FACS analysis revealed 1.2 +/- 0.22% CD34(+) cells within the isolated UCMNCs from which AcLDL(+) endothelial cells were cultured in vitro. All animals survived surgery. TTE revealed grade II-III pulmonary regurgitation in both groups. Pressure-volume loops under dobutamine stress showed significantly improved RV diastolic function in the cell group (dP/dt(min): p = 0.043; E(ed): p = 0.009). CD31 staining indicated a significantly enhanced number of microvessels in the region of UCMNC implantation in the cell group (p < 0.001). No adverse tissue changes were observed. TAP augmentation and pulmonary annulus distortion without cardiopulmonary bypass constitutes a valid large animal model mimicking the surgical repair of tetralogy of Fallot. Our results indicate that the chronically volume-overloaded RV profits from autologous UCMNC implantation by enhanced diastolic properties with a probable underlying mechanism of increased angiogenesis.

Concise Review: Pluripotent Stem Cell-Derived Cardiac Cells, A Promising Cell Source for Therapy of Heart Failure: Where Do We Stand?

“…Paracrine effect of cells without their regenerative potential is likely to be far from sufficient to improve RV function. As an example, human or autologous umbilical cord blood mononuclear and myogenic cells which did not give rise to any cardiomyocyte have been used to prevent or treat the RV dysfunction, and disappointing results regarding RV systolic function were reported . By contrast to such cell types, pluripotent stem cell‐derived cardiac progenitors, due to their proliferation and differentiation capabilities, appear as the most interesting candidates to regenerate the RV myocardium.…”

The Right Heart in Congenital Heart Disease, Mechanisms and Recent Advances

“…One of the main reasons may be that the mainstay of therapy is corrective surgery and that stem cell therapy is still at early stages of development. In a recent study by Yerebakan et al, autologous umbilical cord blood mononuclear cell transplantation preserves right ventricular function, especially diastolic properties, in a model of chronic RV volume overload [98]. …”

Potential Uses of Cord Blood in Cardiac Surgery

“…they may develop left ventricular dysfunction as well as a consequence of epicardial coronary artery disease. Given the existing shortage of hearts for cardiac replacement and the uncertainties of ventricular device support in this population, restoration of their ventricular function with cell-based therapies [36] could have significant impact on the lives of many.…”