Background: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with no-obstructive CAD (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary (IC) autologous CD34+ cell therapy for CED.

Methods: Twenty NOCAD patients with invasively-diagnosed CED and persistent angina despite maximally-tolerated medical therapy (MTMT) underwent baseline exercise stress test (EST), GCSF-mediated CD34+ cell-mobilization, leukapheresis, and selective 1×105 CD34+ cells/kg infusion into LAD. Invasive CED evaluation and EST were repeated 6-months after cell infusion. Primary endpoints were safety and effect of IC autologous CD34+ cell therapy on CED at 6-months follow-up. Secondary endpoints were change in CCS angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire (SAQ) scores, and exercise time at 6-months. Change in CED was compared to that of 51 historic-control NOCAD patients treated with MTMT alone.

Results: Mean age was 52{plus minus}13 years, 75% women. No death, myocardial infarction, or stroke occurred. IC CD34+ cell infusion improved microvascular CED [% acetylcholine-mediated coronary blood flow increased from 7.2 (-18.0-32.4) to 57.6 (16.3-98.3) %, p=0.014], decreased CCS angina class (3.7{plus minus}0.5 to 1.7{plus minus}0.9, Wilcoxon signed-rank test p=0.00018) and sublingual nitroglycerin use/day [1 (0.4-3.5) to 0 (0-1), Wilcoxon signed-rank test p=0.00047], and improved all SAQ scores with no significant change in exercise time at 6-months follow-up. Historic-control patients had no significant change in CED.

Conclusion: A single IC autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Clinical Trial Registration: NCT03471611