Progenitor Hematopoietic Cells Implantation Improves Functional Capacity of End Stage Coronary Artery Disease Patients with Advanced Heart Failure

Abstract

Background. Proangiogenic Hematopoietic Cells (PHC) which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure. Methods. Patients with symptomatic heart failure despite guideline directed medical therapy and LVEF less than 35% were included. Peripheral blood mononuclear cells were isolated, cultivated for 5 days, and then harvested. Flow cytometry and cell surface markers were used to characterize PHC. The PHC were delivered retrogradely via sinus coronarius. Echocardiography, myocardial perfusion, and clinical and functional data were analyzed up to 1-year observation. Results. Of 30 patients (56.4 ± 7.40 yo) preimplant NT proBNP level is 5124.5 ± 4682.50 pmol/L. Harvested cells characterized with CD133, CD34, CD45, and KDR showed 0.87 ± 0.41, 0.63 ± 0.66, 99.00 ± 2.60, and 3.22 ± 3.79%, respectively. LVEF was improved (22 ± 5.68 versus 26.8 ± 7.93, p < 0.001) during short and long term observation. Myocardial perfusion significantly improved 6 months after treatment. NYHA Class and six-minute walk test are improved during short term and long term follow-up. Conclusion. Expanded peripheral blood PHC implantation using retrograde delivery approach improved LV systolic function, myocardial perfusion, and functional capacity.

Figure 1

Retrograde delivery. Coronary sinus is cannulated using AL-1 catheter. Venogram shows anterolateral vein branches associated with infarcted area. The vein branch which is end vessel is selected as target vein. End vessel is confirmed by contrast injection through inflation over the wire balloon which shows no collateral (inset). Stem cells were delivered via the same balloon which is kept inflated for 15 minutes afterward.

Figure 2

Observation of the cultured PMNCs. On day 1, the cells still display morphology resembling mononuclear cells (a). After 5-day culture, some of the cells exhibit spindle-like morphology (arrow), indicating that the cells are becoming more eEPCs like (b). Original magnification 100x.

Figure 3

After 5 days of culture in the presence of VEGF and statin, the cells were stained with DAPI (a), UEA-1 lectin (b), Dil-acetylated LDL (c), and merge image (d). The cells exhibit the ability to bind lectin and uptake ac-LDL, one of the characteristics of eEPCs. Original magnification ×100.

Figure 4

Myocardial perfusion. Left and right panel represent pre- and post-stem cell implantation status, respectively. Upper panels are visual interpretation that comprise short axis view, horizontal long axis view, and vertical long axis view during stress (Str) and rest (Rst). Lower panels are semiquantitative interpretation. Post-stem cell implantation shows more massive perfused myocard as presented with green and yellow color. Semiquantitative interpretation shows less area with score of 4 meaning less area with absent perfusion or nonviable cells. The Summed Stress Score (SSS) and Summed Rest Score (SRS) reduced after stem cell implantation.