Autologous CD34⁺ Cell Therapy for Refractory Angina: 2-Year Outcomes from the ACT34-CMI Study

Abstract

An increasing number of patients have refractory angina despite optimal medical therapy and are without further revascularization options. Preclinical studies indicate that human CD34 stem cells can stimulate new blood vessel formation in ischemic myocardium, improving perfusion and function. In ACT34-CMI (N = 167), patients treated with autologous CD34 stem cells had improvements in angina and exercise time at 6 and 12 months compared to placebo; however, the longer-term effects of this treatment are unknown. ACT34 was a phase II randomized, double-blind, placebo-controlled clinical trial comparing placebo, low dose (1 × 10 CD34/kg body weight), and high dose (5 × 10 CD34/kg) using intramyocardial delivery into the ischemic zone following NOGA mapping. To obtain longer-term safety and efficacy in these patients, we compiled data of major adverse cardiac events (MACE; death, myocardial infarction, acute coronary syndrome, or heart failure hospitalization) up to 24 months as well as angina and quality of life assessments in patients who consented for 24-month follow-up. A total of 167 patients with class III-IV refractory angina were randomized and completed the injection procedure. The low-dose-treated patients had a significant reduction in angina frequency (p = 0.02, 0.035) and improvements in exercise tolerance testing (ETT) time (p = 0.014, 0.017) compared to the placebo group at 6 and 12 months. At 24 months, patients treated with both low-and high-dose CD34 cells had significant reduction in angina frequency (p = 0.03). At 24 months, there were a total of seven deaths (12.5%) in the control group versus one (1.8%) in the low-dose and two (3.6%) in the high-dose (p = 0.08) groups. At 2 years, MACE occurred at a rate of 33.9%, 21.8%, and 16.2% in control, low-, and high-dose patients, respectively (p = 0.08). Autologous CD34 cell therapy was associated with persistent improvement in angina at 2 years and a trend for reduction in mortality in no-option patients with refractory angina.

Reversal of Bone Marrow Mobilopathy and Enhanced Vascular Repair by Angiotensin-(1-7) in Diabetes

“…Currently, cell-based therapies are being tested extensively for the treatment of cardiovascular diseases in several clinical trials (9–11). Individuals with diabetes who have cardiovascular complications are best treated with cell-based therapies; however, this approach is currently not feasible because diabetes causes severe impairment in BMPC mobilization, also known as bone marrow mobilopathy (2,3).…”

Evaluation of tenogenic differentiation potential of selected subpopulations of human adipose‐derived stem cells

“…Remarkably, mobilized peripheral blood CD34+ progenitors have been already employed clinically for the prevention of graft-versus-hostdisease in HLA-mismatched recipients (Handgretinger et al, 2001) and for the treatment of refractory angina (Henry et al, 2016). Furthermore, several preclinical studies reported utility of MSC subpopulations for various orthopaedic applications, for instance, CD105depleted ASCs demonstrated enhanced osteogenic differentiation, whereas CD271+ cells from synovial membrane improved cartilage repair (Pérez-Silos et al, 2016).…”

Management of Refractory Angina Pectoris

“…43,44 Cell Therapy progenitor cells in patients with RA. [45][46][47][48][49][50][51][52][53][54] After delivery, cellular products poorly engraft and are thought to improve ischaemia by promoting neovascularisation through paracrine effects although the precise mechanisms have not been fully elucidated. [55][56][57] Fischer 62,63 These issues must be resolved before cellular therapy can enter routine clinical practice.…”