Abstract P034: Bone Marrow--Derived Cells Are Not an Essential Component in Cardiosphere Formation

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Jianqin Ye ◽  
Andrew Boyle ◽  
Yerem Yeghiazarians
Keyword(s):  
Myocardial Infarction ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Small Cells ◽  
Immunomagnetic Beads ◽  
Cell Component ◽  
Post Surgery ◽  
C57bl Mice ◽  
Bone Marrow Derived Cells

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.

Abstract 22: CXCR4 Expression on Endogenous Bone Marrow Stem/Progenitor Cells is Crucial for Preservation of Myocardial Function After MI

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Marcin Wysoczynski ◽  
Mitesh Solanki ◽  
Rakesh Ponnapureddy ◽  
Rakesh Gadde ◽  
Roberto Bolli ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Bone Marrow Cells ◽  
Systolic Function ◽  
Myocardial Dysfunction ◽  
Lv Function ◽  
Wild Type ◽  
Marrow Cells

Background: Studies examining the role of bone marrow CXCR4 in the response to myocardial infarction (MI) using the CXCR4 antagonist AMD3100 in animal myocardial infarction (MI) models are inconclusive. Chronic AMD3100 administration exacerbated injury and myocardial dysfunction while bolus injection immediately post-MI reduced size of the injury with improvement of systolic function. Aims: As MI mobilizes bone marrow stem/progenitor cells and immune cells into peripheral blood which then home to injured myocardium to facilitate and impair, respectively, regeneration and healing we were interested in the role of bone marrow CXCR4 on functional recovery, angiogenesis, and cardiomyogenesis. Experimental Approach: To define the role of CXCR4 in the bone marrow we generated chimeras with bone marrow from CXCR4 flox/flox mice. Wild type mice were transplanted with CXCR4 flox/flox or CXCR4 flox/flox UBQ Cre bone marrow cells after a lethal dose of irradiation. CXCR4 deletion was induced 5 weeks after transplant with Tamoxifen. The coronary artery was ligated after another two weeks. Function was evaluated five weeks post MI function by echo and pathology analysis was performed to measure scar size, collagen content, hypertrophy, capillary counts, CSCs counts, angiogenesis and cardiomyogenesis. Results: compared to wild type, mice with CXCR4 KO bone marrow had impaired LV systolic function evaluated 5 weeks post-MI by echocardiography. Morphometric analysis of Masson’s Trichrome stained sections confirmed LV exacerbated chamber enlargement (expansion index), larger scar and decreased infarcted wall thickness in mice with bone marrow cells deficient for CXCR4. More detailed analysis revealed c-kit positive CSC numbers were decreased as were proliferating c-kit CSC indicated by Ki67 staining. Decreased proliferation also correlated with reduced numbers of newly formed myocytes (αsarcomeric actin pos /BrdU pos ). Capillary and arteriole counts were also reduced in infarcted hearts of mice with CXCR4 KO bone marrow compared to wild type. Conclusion: based on these findings we can conclude that CXCR4 is necessary for bone marrow cell homing to infarcted myocardium to preserve LV function, regenerate lost myocardium, and promote angiogenesis.

scholarly journals Exploring the anti-apoptotic role of HAX-1 versus BCL-XL in cytokine-dependent bone marrow-derived cells from mice

FEBS Letters ◽  
2014 ◽  
Vol 588 (17) ◽  
pp. 2921-2927 ◽  
Author(s):  
Alicja Trebinska ◽  
Kari Högstrand ◽  
Alf Grandien ◽  
Ewa A. Grzybowska ◽  
Bengt Fadeel
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Derived Cells

scholarly journals A novel role for bone marrow-derived cells to recover damaged keratinocytes from radiation-induced injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junko Okano ◽  
Yuki Nakae ◽  
Takahiko Nakagawa ◽  
Miwako Katagi ◽  
Tomoya Terashima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Underlying Mechanism ◽  
Basal Cells ◽  
Barrier Dysfunction ◽  
Skin Injury ◽  
Accelerated Proliferation ◽  
Radiation Induced ◽  
Bone Marrow Derived Cells ◽  
Injury Recovery

AbstractExposure to moderate doses of ionizing radiation (IR), which is sufficient for causing skin injury, can occur during radiation therapy as well as in radiation accidents. Radiation-induced skin injury occasionally recovers, although its underlying mechanism remains unclear. Moderate-dose IR is frequently utilized for bone marrow transplantation in mice; therefore, this mouse model can help understand the mechanism. We had previously reported that bone marrow-derived cells (BMDCs) migrate to the epidermis-dermis junction in response to IR, although their role remains unknown. Here, we investigated the role of BMDCs in radiation-induced skin injury in BMT mice and observed that BMDCs contributed to skin recovery after IR-induced barrier dysfunction. One of the important mechanisms involved the action of CCL17 secreted by BMDCs on irradiated basal cells, leading to accelerated proliferation and recovery of apoptosis caused by IR. Our findings suggest that BMDCs are key players in IR-induced skin injury recovery.

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