Age-Dependent Availability and Functionality of Bone Marrow Stem Cells in an Experimental Model of Acute and Chronic Myocardial Infarction

被引：15

作者：

Ayala-Lugo, Ana ^{[2
,4
]}

Tavares, Angela M. V. ^{[7
]}

Paz, Ana H. R. ^{[2
]}

Alegretti, Ana ^{[2
]}

Miquelito, Ludmila ^{[2
]}

Bock, Hugo ^{[6
]}

Giugliani, Roberto ^{[3
,6
,10
]}

Clausell, Nadine ^{[5
,8
]}

Cirne-Lima, Elizabeth ^{[2
,9
]}

Rohde, Luis E. ^{[1
,5
,8
]}

机构：

[1] Hosp Clin Porto Alegre, Heart Failure & Transplant Unit, Cardiovasc Res Lab, BR-90035003 Porto Alegre, RS, Brazil

[2] Hosp Clin Porto Alegre, Embriol & Cell Differentiat Lab, BR-90035003 Porto Alegre, RS, Brazil

[3] Hosp Clin Porto Alegre, Med Genet Serv, BR-90035003 Porto Alegre, RS, Brazil

[4] Univ Fed Rio Grande do Sul, Postgrad Program Genet & Mol Biol, Porto Alegre, RS, Brazil

[5] Univ Fed Rio Grande do Sul, Postgrad Program Cardiol & Cardiovasc Sci, Porto Alegre, RS, Brazil

[6] Univ Fed Rio Grande do Sul, Postgrad Program Biol Sci Biochem, Porto Alegre, RS, Brazil

[7] Univ Fed Rio Grande do Sul, Cardiovasc Physiol Lab, Dept Physiol, Porto Alegre, RS, Brazil

[8] Univ Fed Rio Grande do Sul, Sch Med, Porto Alegre, RS, Brazil

[9] Univ Fed Rio Grande do Sul, Sch Vet, Porto Alegre, RS, Brazil

[10] Univ Fed Rio Grande do Sul, Biosci Inst, Porto Alegre, RS, Brazil

来源：

CELL TRANSPLANTATION | 2011年 / 20卷 / 03期

关键词：

Cell therapy; Myocardial infarction (MI); Aging;

D O I：

10.3727/096368909X519283

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 stern 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.

引用

页码：407 / 419

页数：13