Bone marrow-derived progenitor cells contribute to lung remodelling after myocardial infarction

Background: Cardiospheres (CS) are composed of heterogeneous population of cells but it is unknown whether bone marrow derived cells are an essential cell component in CS formation. Methods: Chimera mice were generated by transplantation of bone morrow cells from GFP transgenic mice to irradiated C57BL mice. Mice were randomized into 3 groups 5 months after transplantation: 1) myocardial infarction; 2) sham operated; 3) un-operated (n=5/group). Hearts were harvested 2-weeks post-surgery. Cardiac explants were cultured and putative cardiosphere forming cells (CFCs) (small cells migrating out from the explants) were collected 14 days later and reseeded on new culture dishes for CS formation. The number of CS from each heart was counted at 3 days. CS cell composition was analyzed by FACS. To further analyze the role of bone marrow derived CD45+ cells in forming CS, CD45+ cells was isolated from CFCs by CD45 antibody coated immunomagnetic beads. The number of CS formed from 1×10 5 putative CFCs, CFCs without CD45+ cells and CD45+ cells from CFCs (n=6-9/cell type) respectively were also counted at 3 days in culture. Results: Compared to sham (122± 23/heart) and un-operated hearts (18± 5/heart), infarcted hearts formed more CS (357± 64/heart, P<0.01). In all groups, irrespective of any surgery, 18.4± 4.5% of cells in CS co-expressed GFP and CD45, indicating they originated in bone marrow. Low percentage of bone marrow stem/progenitor cells (3.9% Sca-1+GFP+CD45+ and 1% c-Kit+GFP+CD45+ cells) were detected in CS, but a high percentage of cells within CS were cardiac stem/progenitor cells (26.3± 9.4% cells were Sca-1+GFP-CD45-, 0.10± 0.04% c-Kit+GFP-CD45-). Depleting CD45+ cells from putative CFCs actually increased the formation of CS (67±10 CS/1×10 5 cells) compared to un-depleted CFCs (51± 6 CS/1×10 5 cells, P<0.0001). Purified CD45+ cells from CFCs did not form CS in culture. Conclusion: Myocardial infarction increases the formation of CS in culture. Bone marrow derived CD45+ cells make up a small percentage of CS, but are not necessary for CS formation.

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Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01260.2008 ◽

2010 ◽

Vol 299 (1) ◽

pp. H125-H133 ◽

Cited By ~ 16

Author(s):

John J. Graham ◽

Warren D. Foltz ◽

Andrea K. Vaags ◽

Michael R. Ward ◽

Yuesong Yang ◽

...

Keyword(s):

Myocardial Infarction ◽

Bone Marrow ◽

Coronary Artery ◽

Ejection Fraction ◽

Cell Viability ◽

Progenitor Cells ◽

Infarct Volume ◽

Post Myocardial Infarction ◽

Bone Marrow Progenitor Cells ◽

Bone Marrow Progenitor

Magnetic resonance imaging (MRI) can track progenitor cells following direct intramyocardial injection. However, in the vast majority of post-myocardial infarction (MI) clinical trials, cells are delivered by the intracoronary (IC) route, which results in far greater dispersion within the myocardium. Therefore, we assessed whether the more diffuse distribution of cells following IC delivery could be imaged longitudinally with MRI. In 11 pigs (7 active, 4 controls), MI was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Seven (0) days [median (interquartile range)] following MI, bone marrow progenitor cells (BMCs) were colabeled with an iron-fluorophore and a cell viability marker and delivered to the left anterior descending coronary artery distal to an inflated over-the-wire percutaneous transluminal coronary angioplasty balloon. T2*-weighted images were used to assess the location of the magnetically labeled cells over a 6-wk period post-MI. Immediately following cell delivery, hypointensity characteristic of the magnetic label was observed in the infarct border rather than within the infarct itself. At 6 wk, the cell signal hypointensity persisted, albeit with significantly decreased intensity. BMC delivery resulted in significant improvement in infarct volume and ejection fraction (EF): infarct volume in cell-treated animals decreased from 7.1 ± 1.5 to 4.9 ± 1.0 ml ( P < 0.01); infarct volume in controls was virtually unchanged at 4.64 ± 2.1 to 4.39 ± 2.1 ml ( P = 0.7). EF in cell-treated animals went from 30.4 ± 5.2% preinjection to 34.5 ± 2.5% 6 wk postinjection ( P = 0.013); EF in control animals went from 34.3 ± 4.7 to 31.9 ± 6.8% ( P = 0.5). Immunohistochemical analysis revealed intracellular colocalization of the iron fluorophore and cell viability dye with the labeled cells continuing to express the same surface markers as at baseline. MRI can track the persistence and distribution of magnetically labeled BMCs over a 6-wk period following IC delivery. Signal hypointensity declines with time, particularly in the first week following delivery. These cells maintain their original phenotype during this time course. Delivery of these cells appears safe and results in improvement in infarct size and left ventricular ejection fraction.

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Autologous bone marrow concentrate enriched in progenitor cells — An adjuvant in the treatment of acute myocardial infarction

International Journal of the Cardiovascular Academy ◽

10.1016/j.ijcac.2016.04.001 ◽

2016 ◽

Vol 2 (2) ◽

pp. 77-83 ◽

Cited By ~ 1

Author(s):

Vinay Sanghi ◽

Dalip Sethi ◽

Kenneth L. Harris ◽

Saniya Gupta ◽

Sheila Kar ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Bone Marrow ◽

Progenitor Cells ◽

Autologous Bone Marrow ◽

Bone Marrow Concentrate ◽

Autologous Bone

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Intracoronary Injection of CD133-Positive Enriched Bone Marrow Progenitor Cells Promotes Cardiac Recovery After Recent Myocardial Infarction

Circulation ◽

10.1161/circulationaha.104.522292 ◽

2005 ◽

Vol 112 (9_supplement) ◽

Cited By ~ 5

Author(s):

Jozef Bartunek ◽

Marc Vanderheyden ◽

Bart Vandekerckhove ◽

Samer Mansour ◽

Bernard De Bruyne ◽

...

Keyword(s):

Myocardial Infarction ◽

Bone Marrow ◽

Progenitor Cells ◽

Left Ventricular ◽

Recent Myocardial Infarction ◽

Stent Restenosis ◽

Intracoronary Administration ◽

Group 2 ◽

In Stent Restenosis ◽

Group 1

Background— Bone marrow CD133-postive (CD133 + ) cells possess high hematopoietic and angiogenic capacity. We tested the feasibility, safety, and functional effects of the use of enriched CD133 + progenitor cells after intracoronary administration in patients with recent myocardial infarction. Methods and Results— Among 35 patients with acute myocardial infarction treated with stenting, 19 underwent intracoronary administration of CD133 + progenitor cells (12.6±2.2×10 6 cells) 11.6±1.4 days later (group 1) and 16 did not (group 2). At 4 months, left ventricular ejection fraction increased significantly in group 1 (from 45.0±2.6% to 52.1±3.5%, P <0.05), but only tended to increase in case-matched group 2 patients (from 44.3±3.1% to 48.6±3.6%, P =NS). Likewise, left ventricular regional chordae shortening increased in group 1 (from 11.5±1.0% to 16.1±1.3%, P <0.05) but remained unchanged in group 2 patients (from 11.1±1.1% to 12.7±1.3%, P =NS). This was paralleled by reduction in the perfusion defect in group 1 (from 28.0±4.1% to 22.5±4.1%, P <0.05) and no change in group 2 (from 25.0±3.0% to 22.6±4.1%, P =NS). In group 1, two patients developed in-stent reocclusion, 7 developed in-stent restenosis, and 2 developed significant de novo lesion of the infarct-related artery. In group 2, four patients showed in-stent restenosis. In group 1 patients without reocclusion, glucose uptake shown by positron emission tomography with 18 fluorodeoxyglucose in the infarct-related territory increased from 51.2±2.6% to 57.5±3.5% ( P <0.05). No stem cell-related arrhythmias were noted, either clinically or during programmed stimulation studies at 4 months. Conclusion— In patients with recent myocardial infarction, intracoronary administration of enriched CD133 + cells is feasible but was associated with increased incidence of coronary events. Nevertheless, it seems to be associated with improved left ventricular performance paralleled with increased myocardial perfusion and viability.

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