Phase I and registry study of autologous bone marrow concentrate evaluated in PDE5 inhibitor refractory erectile dysfunction.

BACKGROUND: Bone marrow mononuclear cells have been successfully utilized for numerous regenerative purposes. In the current study, patients suffering from erectile dysfunction (ED) unresponsive to phosphodiesterase 5 inhibitors were administered autologous bone marrow concentrate delivered intracavernously utilizing a point of care FDA cleared medical device. METHODS: A total of 40 patients were treated in the primary trial and 100 in the clinical registry, with the longest follow up of 12 months. RESULTS: Minimal treatment associated adverse effects where observed related to short term bruising at the site of harvest or injection. No long-term adverse events were noted related to the intervention. Mean improvements in IIEF-5 score were 2 in the Caverstem 1.0 low dose group, 3 in the high dose Caverstem 1.0 group and 9 in the Caverstem 2.0 group. Furthermore, improvements peaked by 3 months and maintained at 6 months follow-up. CONCLUSION: These data support the safety and efficacy of point of care, minimally to non-manipulated, non-expanded bone marrow concentrate for the treatment of ED. Trial registration Funded by Creative Medical Health, Inc.; Clinicaltrials.gov number: NCT03699943; https://clinicaltrials.gov/ct2/show/NCT03699943?term=caverstem&rank=1; initially registered December 12, 2015.

RESCUE-HF Trial: Retrograde Delivery of Allogeneic Umbilical Cord Lining Subepithelial Cells in Patients With Heart Failure.

Cell therapy is an evolving option for patients with end-stage heart failure. First-generation cell therapy trials have had marginal success. Our goal was to evaluate retrograde delivery of allogeneic umbilical cord subepithelial cells (UCSECs) in patients with heart failure. A prospective open-label dose escalation study of the safety and feasibility of UCSECs infused retrogradely into the coronary sinus was performed. Patients received a single dose of either 100 million (M), 200M, or 400M cells. The patients were followed for 2 years. Twenty-four patients were successfully enrolled in the study. The patients had UCSEC infusion without procedure-related complications. The ejection fraction in patients receiving UCSECs demonstrated improvement compared to baseline; from 25.4% (±5.5) at screening to 34.9% (±4.1) at 12 months. End-systolic diameter decreased significantly from 59.9 (±5.3) mm to 52.6 (±2.7) mm (p < 0.05). Retrograde UCSEC delivery was safe and feasible in all three dosage groups. Patients receiving 200M and 400M UCSECs showed signs of early improvement in left ventricular ejection fraction (LVEF) and remodeling. This study provides the basis for a larger clinical trial in heart failure (HF) patients using the middle or high dose of UCSECs.

Safety and feasibility of percutaneous retrograde coronary sinus delivery of autologous bone marrow mononuclear cell transplantation in patients with chronic refractory angina.

BACKGROUND: Chronic refractory angina is a challenging clinical problem with limited treatment options. The results of early cardiovascular stem cell trials using ABMMC have been promising but have utilized intracoronary or intramyocardial delivery. The goal of the study was to evaluate the safety and early efficacy of autologous bone marrow derived mononuclear cells (ABMMC) delivered via percutaneous retrograde coronary sinus perfusion (PRCSP) to treat chronic refractory angina (CRA). METHODS: From May 2005 to October 2006, 14 patients, age 68 +/- 20 years old, with CRA and ischemic stress-induced myocardial segments assessed by SPECT received a median 8.19*10(8) ± 4.3*10(8) mononuclear and 1.65*10(7) ± 1.42*10(7) CD34(+) cells by PRCSP. RESULTS: ABMMC delivery was successful in all patients with no arrhythmias, elevated cardiac enzymes or complications related to the delivery. All but one patient improved by at least one Canadian Cardiovascular Society class at 2 year follow-up compared to baseline (p < 0.001). The median baseline area of ischemic myocardium by SPECT of 38.2% was reduced to 26.5% at one year and 23.5% at two years (p = 0.001). The median rest left ventricular ejection fraction by SPECT at baseline was 31.2% and improved to 35.5% at 2 year follow up (p = 0.019). CONCLUSIONS: PRCSP should be considered as an alternative method of delivery for cell therapy with the ability to safely deliver large number of cells regardless of coronary anatomy, valvular disease or myocardial dysfunction. The clinical improvement in angina, myocardial perfusion and function in this phase 1 study is encouraging and needs to be confirmed in randomized placebo controlled trials.