EFFICACY OF CD34+ STEM CELL THERAPY IN NON-ISCHEMIC DILATED CARDIOMYOPATHY IS ABSENT IN PATIENTS WITH DIABETES BUT PRESERVED IN PATIENTS WITH INSULIN RESISTANCE

Autor: Gregor Zemljic, Francois Haddad, Matjaz Sever, Gregor Poglajen, Bojan Vrtovec, Peter Černelč, Ulrich P. Jorde, Nika Aleksandra Kravos, Mojca Jensterle, Joseph C. Wu, Andrej Janez, Marko Cukjati
Rok vydání: 2015
Předmět:
0301 basic medicine
Blood Glucose
Male
Time Factors
Diabetic Cardiomyopathies
medicine.medical_treatment
CD34
Antigens
CD34

030204 cardiovascular system & hematology
Gastroenterology
Ventricular Function
Left

Cell therapy
0302 clinical medicine
Diabetic cardiomyopathy
Natriuretic Peptide
Brain

Insulin
Stem Cells
Dilated cardiomyopathy
General Medicine
Stem-cell therapy
Middle Aged
Phenotype
Treatment Outcome
cardiovascular system
Cardiology
Female
Non ischemic
Stem cell
Cardiology and Cardiovascular Medicine
Adult
Cardiomyopathy
Dilated

medicine.medical_specialty
03 medical and health sciences
Young Adult
Insulin resistance
Diabetes mellitus
Internal medicine
medicine
Humans
Enabling Technologies for Cell-Based Clinical Translation
In patient
cardiovascular diseases
Aged
business.industry
Stroke Volume
Cell Biology
Recovery of Function
medicine.disease
Peptide Fragments
030104 developmental biology
Endocrinology
Heart failure
Insulin Resistance
business
Biomarkers
Developmental Biology
Stem Cell Transplantation
Zdroj: Journal of the American College of Cardiology. 65:A963
ISSN: 0735-1097
Popis: We evaluated the association of diabetes and insulin resistance with the response to cell therapy in patients with nonischemic dilated cardiomyopathy (DCM). A total of 45 outpatients with DCM received granulocyte colony-stimulating factor for 5 days. CD34+ cells were then collected by apheresis and injected transendocardially. Twelve patients had diabetes mellitus (DM group), 17 had insulin resistance (IR group), and 16 displayed normal glucose metabolism (no-IR group). After stimulation, we found higher numbers of CD34+ cells in the IR group (94 ± 73 × 106 cells per liter) than in the no-IR group (54 ± 35 × 106 cells per liter) or DM group (31 ± 20 × 106 cells per liter; p = .005). Similarly, apheresis yielded the highest numbers of CD34+ cells in the IR group (IR group, 216 ± 110 × 106 cells; no-IR group, 127 ± 82 × 106 cells; DM group, 77 ± 83 × 106 cells; p = .002). Six months after cell therapy, we found an increase in left ventricular ejection fraction in the IR group (+5.6% ± 6.9%) and the no-IR group (+4.4% ± 7.2%) but not in the DM group (−0.9% ± 5.4%; p = .035). The N-terminal pro-brain natriuretic peptide levels decreased in the IR and no-IR groups, but not in the DM group (−606 ± 850 pg/ml; −698 ± 1,105 pg/ml; and +238 ± 963 pg/ml, respectively; p = .034). Transendocardial CD34+ cell therapy appears to be ineffective in DCM patients with diabetes. IR was associated with improved CD34+ stem cell mobilization and a preserved clinical response to cell therapy. Significance The present study is the first clinical study directly evaluating the effects of altered glucose metabolism on the efficacy of CD34+ stem cell therapy in patients with nonischemic dilated cardiomyopathy. The results offer critical insights into the physiology of stem cell mobilization in heart failure and possibly an explanation for the often conflicting results obtained with stem cell therapy for heart failure. These results demonstrate that patients with dilated cardiomyopathy and diabetes do not benefit from autologous CD34+ cell therapy. This finding could serve as a useful tool when selecting heart failure patients for future clinical studies in the field of stem cell therapy.
Databáze: OpenAIRE