Tags

Type your tag names separated by a space and hit enter

Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease.
Circulation. 2004 Apr 06; 109(13):1615-22.Circ

Abstract

BACKGROUND

Cell therapy with bone marrow-derived stem/progenitor cells is a novel option for improving neovascularization and cardiac function in ischemic heart disease. Circulating endothelial progenitor cells in patients with coronary heart disease are impaired with respect to number and functional activity. However, whether this impairment also extends to bone marrow-derived mononuclear cells (BM-MNCs) in patients with chronic ischemic cardiomyopathy (ICMP) is unclear.

METHODS AND RESULTS

BM-MNCs were isolated from bone marrow aspirates in 18 patients with ICMP (ejection fraction, 38+/-11%) and 8 healthy control subjects (controls). The number of hematopoietic stem/progenitor cells (CD34+/CD133+), CD49d(+) (VLA-4) cells, and CXCR4+ cells did not differ between the 2 groups. However, the colony-forming capacity of BM-MNCs from patients with ICMP was significantly lower compared with BM-MNCs from healthy controls (37.3+/-25.0 versus 113.8+/-70.4 granulocyte-macrophage colony-forming units; P=0.009). Likewise, the migratory response to stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) was significantly reduced in BM-MNCs derived from patients with ICMP compared with BM-MNCs from healthy controls (SDF-1, 46.3+/-26.2 versus 108.6+/-40.4 cells/microscopic field, P<0.001; VEGF, 34+/-24.2 versus 54.8+/-29.3 cells/microscopic field, P=0.027). To assess the in vivo relevance of these findings, we tested the functional activity of BM-MNCs to improve neovascularization in a hindlimb animal model using nude mice. Two weeks after ligation of the femoral artery and intravenous injection of 5x10(5) BM-MNCs, laser Doppler-derived relative limb blood flow in mice treated with BM-MNCs from patients with ICMP was significantly lower compared with mice treated with BM-MNCs from healthy controls (0.45+/-0.14 versus 0.68+/-0.15; P<0.001). The in vivo neovascularization capacity of BM-MNCs closely correlated with the in vitro assessment of SDF-1-induced migration (r=0.78; P<0.001) and colony-forming capacity (r=0.74; P<0.001).

CONCLUSIONS

BM-MNCs isolated from patients with ICMP have a significantly reduced migratory and colony-forming activity in vitro and a reduced neovascularization capacity in vivo despite similar content of hematopoietic stem cells. This functional impairment of BM-MNCs from patients with ICMP may limit their therapeutic potential for clinical cell therapy.

Authors+Show Affiliations

Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15037527

Citation

Heeschen, Christopher, et al. "Profoundly Reduced Neovascularization Capacity of Bone Marrow Mononuclear Cells Derived From Patients With Chronic Ischemic Heart Disease." Circulation, vol. 109, no. 13, 2004, pp. 1615-22.
Heeschen C, Lehmann R, Honold J, et al. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation. 2004;109(13):1615-22.
Heeschen, C., Lehmann, R., Honold, J., Assmus, B., Aicher, A., Walter, D. H., Martin, H., Zeiher, A. M., & Dimmeler, S. (2004). Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation, 109(13), 1615-22.
Heeschen C, et al. Profoundly Reduced Neovascularization Capacity of Bone Marrow Mononuclear Cells Derived From Patients With Chronic Ischemic Heart Disease. Circulation. 2004 Apr 6;109(13):1615-22. PubMed PMID: 15037527.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. AU - Heeschen,Christopher, AU - Lehmann,Ralf, AU - Honold,Jörg, AU - Assmus,Birgit, AU - Aicher,Alexandra, AU - Walter,Dirk H, AU - Martin,Hans, AU - Zeiher,Andreas M, AU - Dimmeler,Stefanie, Y1 - 2004/03/22/ PY - 2004/3/24/pubmed PY - 2004/7/24/medline PY - 2004/3/24/entrez SP - 1615 EP - 22 JF - Circulation JO - Circulation VL - 109 IS - 13 N2 - BACKGROUND: Cell therapy with bone marrow-derived stem/progenitor cells is a novel option for improving neovascularization and cardiac function in ischemic heart disease. Circulating endothelial progenitor cells in patients with coronary heart disease are impaired with respect to number and functional activity. However, whether this impairment also extends to bone marrow-derived mononuclear cells (BM-MNCs) in patients with chronic ischemic cardiomyopathy (ICMP) is unclear. METHODS AND RESULTS: BM-MNCs were isolated from bone marrow aspirates in 18 patients with ICMP (ejection fraction, 38+/-11%) and 8 healthy control subjects (controls). The number of hematopoietic stem/progenitor cells (CD34+/CD133+), CD49d(+) (VLA-4) cells, and CXCR4+ cells did not differ between the 2 groups. However, the colony-forming capacity of BM-MNCs from patients with ICMP was significantly lower compared with BM-MNCs from healthy controls (37.3+/-25.0 versus 113.8+/-70.4 granulocyte-macrophage colony-forming units; P=0.009). Likewise, the migratory response to stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) was significantly reduced in BM-MNCs derived from patients with ICMP compared with BM-MNCs from healthy controls (SDF-1, 46.3+/-26.2 versus 108.6+/-40.4 cells/microscopic field, P<0.001; VEGF, 34+/-24.2 versus 54.8+/-29.3 cells/microscopic field, P=0.027). To assess the in vivo relevance of these findings, we tested the functional activity of BM-MNCs to improve neovascularization in a hindlimb animal model using nude mice. Two weeks after ligation of the femoral artery and intravenous injection of 5x10(5) BM-MNCs, laser Doppler-derived relative limb blood flow in mice treated with BM-MNCs from patients with ICMP was significantly lower compared with mice treated with BM-MNCs from healthy controls (0.45+/-0.14 versus 0.68+/-0.15; P<0.001). The in vivo neovascularization capacity of BM-MNCs closely correlated with the in vitro assessment of SDF-1-induced migration (r=0.78; P<0.001) and colony-forming capacity (r=0.74; P<0.001). CONCLUSIONS: BM-MNCs isolated from patients with ICMP have a significantly reduced migratory and colony-forming activity in vitro and a reduced neovascularization capacity in vivo despite similar content of hematopoietic stem cells. This functional impairment of BM-MNCs from patients with ICMP may limit their therapeutic potential for clinical cell therapy. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/15037527/Profoundly_reduced_neovascularization_capacity_of_bone_marrow_mononuclear_cells_derived_from_patients_with_chronic_ischemic_heart_disease_ L2 - https://www.ahajournals.org/doi/10.1161/01.CIR.0000124476.32871.E3?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -