The impact of patient co-morbidities on the regenerative capacity of cardiac explant-derived stem cells

Autor: Seth Mount, Darryl R. Davis, Melanie Villanueva, N. Latham, Duncan J. Stewart, Bu-Khanh Lam, Megan E. Fitzpatrick, Everad L. Tilokee, Marc Ruel, Audrey E. Mayfield
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Angiogenesis
medicine.medical_treatment
Myocardial Infarction
Gene Expression
Medicine (miscellaneous)
Comorbidity
030204 cardiovascular system & hematology
Exosomes
Ventricular Function
Left
Mice
0302 clinical medicine
Mice
Inbred NOD
Medicine
Myocardial infarction
education.field_of_study
Stem cell
Chemotaxis
Stem Cells
3. Good health
Cytokine
Echocardiography
Molecular Medicine
Stromal cell
Primary Cell Culture
Population
Neovascularization
Physiologic
Heart failure
Biochemistry
Genetics and Molecular Biology (miscellaneous)
03 medical and health sciences
Precursor cell
Animals
Humans
Heart Atria
Acute Coronary Syndrome
education
Interleukin-6
business.industry
Research
Coronary Stenosis
Stroke Volume
Cell Biology
Atherosclerosis
medicine.disease
Chemokine CXCL12
Disease Models
Animal
030104 developmental biology
Immunology
Cell transplantation
business
Stem Cell Transplantation
Zdroj: Stem Cell Research & Therapy
ISSN: 1757-6512
DOI: 10.1186/s13287-016-0321-4
Popis: Background Although patient-sourced cardiac stem cells repair damaged myocardium, the extent to which medical co-morbidities influence cardiac-derived cell products is uncertain. Therefore, we investigated the influence of atherosclerotic risk factors on the regenerative performance of human cardiac explant-derived cells (EDCs). Methods In this study, the Long Term Stratification for survivors of acute coronary syndromes model was used to quantify the burden of cardiovascular risk factors within a group of patients with established atherosclerosis. EDCs were cultured from human atrial appendages and injected into immunodeficient mice 7 days post-left coronary ligation. Cytokine arrays and enzyme linked immunoassays were used to determine the release of cytokines by EDCs in vitro, and echocardiography was used to determine regenerative capabilities in vivo. Results EDCs sourced from patients with more cardiovascular risk factors demonstrated a negative correlation with production of pro-healing cytokines (such as stromal cell derived factor 1α) and exosomes which had negative effects on the promotion of angiogenesis and chemotaxis. Reductions in exosomes and pro-healing cytokines with accumulating medical co-morbidities were associated with increases in production of the pro-inflammatory cytokine interleukin-6 (IL-6) by EDCs. Increased patient co-morbidities were also correlated with significant attenuation in improvements of left ventricular ejection fraction. Conclusions The regenerative performance of the earliest precursor cell population cultured from human explant tissue declines with accumulating medical co-morbidities. This effect is associated with diminished production of pro-cardiogenic cytokines and exosomes while IL-6 is markedly increased. Predictors of cardiac events demonstrated a lower capacity to support angiogenesis and repair injured myocardium in a mouse model of myocardial infarction.
Databáze: OpenAIRE
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