title: Age-dependent availability and functionality of bone marrow stem cells in an experimental model of acute and chronic myocardial infarction.
abstract: The aim of this study was to investigate the effect of aging and timing of left ventricular ischemic injury on the availability and functionality of stem cells. We studied young and aged male inbred Lewis rats that were used as donors of bone marrow mononuclear cells (BM-MNCs), divided in four experimental groups: controls, sham operated, 48 h post-myocardial infarction (MI), and 28 days post-MI. In vitro studies included flow cytometry analysis, hematopoietic colony-forming capacity, and invasion assays of migration capacity. BM-MNCs from these groups were transplanted in female rats after MI induction. Late engraftment was evaluated by real-time PCR of the SRY chromosome. Percentage of CD34+/CD45+(low) cells was similar among different experimental groups in young rats, but was significantly higher in aged animals (p < 0.001), particularly 28 days post-MI. KDR+/CD34+ cells were increased 48 h after MI and decreased 28 days post-MI in young animals, while they were profoundly reduced in the aged group (p < 0.001). Triple staining for CD44+/CD29+/CD71+ cells was similar in different groups of aged rats, but we observed an intense increase 48 h post-MI in young animals. Colony-forming units and cytokine-induced migration were significantly attenuated 28 days after the MI. Late engraftment in infarcted transplanted female hearts was present, but considerably heterogeneous. Finally, recovery of left ventricular systolic function in transplanted female recipients was significantly influenced by donors' BM-MNCs groups (p < 0.01). We have demonstrated that aging and timing of myocardial injury are factors that may act synergistically in determining stem cell availability and function. Such interaction should be considered when planning new cell therapy strategies for acute and chronic ischemic heart disease in the clinical arena.
authors.affiliation: Embriology and Cell Differentiation Laboratory, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre, RS, Brazil.
authors.forename: Ana
authors.initials: A
authors.lastname: Ayala-Lugo
authors.forename: Angela M V
authors.initials: AM
authors.lastname: Tavares
authors.forename: Ana H R
authors.initials: AH
authors.lastname: Paz
authors.forename: Ana
authors.initials: A
authors.lastname: Alegretti
authors.forename: Ludmila
authors.initials: L
authors.lastname: Miquelito
authors.forename: Hugo
authors.initials: H
authors.lastname: Bock
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Nadine
authors.initials: N
authors.lastname: Clausell
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cirne-Lima
authors.forename: Luis E
authors.initials: LE
authors.lastname: Rohde
mesh_terms: D000208:Acute Disease; D000375:Aging; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D024282:Genes, sry; D006352:Heart Ventricles / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000601:surgery / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D011990:Receptors, Transferrin / Q000378:metabolism; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; C068126:CD71 antigen; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D011990:Receptors, Transferrin; D040301:Vascular Endothelial Growth Factor Receptor-2