BackgroundChronic 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).MethodsFrom 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*108 ± 4.3*108 mononuclear and 1.65*107 ± 1.42*107 CD34+ cells by PRCSP..ResultsABMMC 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).ConclusionsPRCSP 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.

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Background: Pilot studies suggest that intracoronary transplantation of unselected ABMMC cells may improve Left Ventricular Ejection Fraction (LVEF) in heart failure (HF) Methods: 18 patients were enrolled and completed 1 year follow up. Patients underwent SPECT evaluation, all had ejection fraction &lt; 35%, 6 patients were randomly allocated to the control group and 12 in the Bone Marrow Cells (BMC) group, median age 65 years old, male/female ratio 17/1; all with ischemic cardiomyopathy. All of cohort had NYHA class of III with maximal medical therapy and median basal LEVF was 28.38% (SD=6.5%). Median number of mononuclear and CD34+ cells infused were 8.1*108 and 1.2*107 respectively in a 50 cc delivered retrograde via coronary sinus approach using balloon occlusion "over wire" for 8 to 10 minutes. No study related adverse events were observed. Results: After a median time of 21 days, patients in the BMC group had relief of dyspnea symptoms and improvement in functional class. At 1 year, NYHA class improved in 92% of the patients in the BMC group by at least 1 class and no improvement in the control group. Mean improvements of LVEF post BMC transplantation were 6.18% (SD=4.94%) and 6.7% (SD=4.07%) at rest and stress SPECT respectively. Rest LVEF at baseline and after one-year follow up between the BMC and control groups demonstrates significant difference (4.9% vs 1.6%, p=0.006), as well as the comparison of change in stress LVEF in both groups (6.7% vs 0.11%, p&lt;0.001). Conclusions: Infusion of progenitor cells into the coronary sinus is safe and feasible in the ischemic HF. It is associated with significant improvement in symptoms, functional capacity and LVEF. Larger randomized studies are in progress to build upon this pilot study. Figure Figure

Background: Recent reports have shown that bone marrow-derived stem cell may contribute to islet regeneration. The goal of our study was to evaluate the safety and efficacy of ABMMC transplantation for patients with IDM. Methods: From June 2005 to January 2007, 28 consecutive patients: 8 Type 1 IDM (T1DM) and 20 Type 2 IDM (T2IDM); who were receiving maximal medical therapy including insulin treatment for 5 years before enrollment. Median time of disease for T2IDM patients was 13 years, without pancreatic islet auto-antibodies. After IRB approval and signed informed consent, bone marrow was harvested and ABMMC were isolated and infused directly into the pancreas via splenic artery using endovascular catheters. Glucose, glycosylated HbA1c and C peptide were measure before and after transplantation. HOMA2 Calculator v2.2 was used to calculated IR and % B (*if Glucose: 3.0 to 25.0 mmol/L and C peptide: 0.2 to 3.5 nmol/L). Results: There were no study related complications. At 1 year follow-up, mean daily insulin requirement was the same in group T1DM and significantly reduced in group T2IDM, from 42.5 to 4.5 U/d (t=7.94, p&lt;0.001). Ten of the twenty (50%) T2IDM established complete insulin independence. Data in table 1. Table 1: Median values PRE POST t p T2IDM (n=20) Fasting Glucose (mmol/L) 10.8 6.6 3.98 0.01 Glycosylated HbA1c (%) 9.6 8.1 3.98 0.01 C peptide (nmol/L) 0.5 0.84 5.11 &lt; 0.01 HOMA 2 IR (n=17)* 2.2 2.26 0.94 0.92 HOMA 2 %B (n=17)* 42.4 130.2 4.9 &lt; 0.01 T1DM (n=8) Fasting Glucose (mmol/L) 10.1 11.1 1.382 0.21 Glycosylated HbA1c (%) 8.7 8.7 0.45 0.66 C peptide (nmol/L) 0.17 0.16 1.00 0.35 Conclusions: The use of ABMMC transplantation for T1DM and T2IDM is safe. In this pilot study, only T2IDM patients have significant improvement in pancreatic function demostrated by better glycemic and HbA1c control, and are associated with a significant independence of the insulin. This has formed for a randomized multi-center study which is currently in progress.