3 results on '"WILLIAM IGNARRO, S"'
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2. Therapeutic targeting of the stem cell niche in experimental hindlimb ischemia
- Author
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Mario Felice Tecce, Pellegrino Biagio Minucci, Ettore Crimi, Antonio Giordano, Claudio Napoli, Louis J. Ignarro, Ettore Varricchio, Carmela Fiorito, Russell E. Byrns, Florio A, Angelo Matarazzo, Bartolomeo Farzati, Maurizio D’Amora, Alfonso Giovane, Filomena de Nigris, Sharon William-Ignarro, Ciro Abbondanza, Antonio Pavan, Francesco Mancini, Antonio Palagiano, Maria Luisa Balestrieri, Napoli, Claudio, WILLIAM IGNARRO, S, Byrns, R, Balestrieri, Maria Luisa, Crimi, E, Farzati, B, Mancini, Fp, de NIGRIS, Filomena, Matarazzo, A, D'Amora, M, Abbondanza, C, Fiorito, C, Giovane, Alfonso, Florio, Anna, Varricchio, E, Palagiano, A, Minucci, Pellegrino Biagio, Tecce, Mf, Giordano, A, Pavan, A, and Ignarro, Lj
- Subjects
Vascular Endothelial Growth Factor A ,Time Factors ,Parathyroid hormone ,Apoptosis ,Hindlimb ,Neovascularization ,Mice ,Cell Movement ,Ischemia ,Granulocyte Colony-Stimulating Factor ,Receptor ,vascular niche ,Hematopoietic stem cell ,General Medicine ,ischemic vascular diseases ,Hematopoietic Stem Cell Mobilization ,Recombinant Proteins ,medicine.anatomical_structure ,Parathyroid Hormone ,Drug Therapy, Combination ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Blood Flow Velocity ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,neoangiogenesis ,bone marrow ,Filgrastim ,Hematopoietic stem cell niche ,Neovascularization, Physiologic ,neoangiogenesi ,Angiopoietin-1 ,medicine ,Animals ,Humans ,RNA, Messenger ,Muscle, Skeletal ,ischemic vascular disease ,Inflammation ,business.industry ,Hematopoietic Stem Cells ,Fibrosis ,Peptide Fragments ,Capillaries ,Rats ,Mice, Inbred C57BL ,Disease Models, Animal ,Oxidative Stress ,Regional Blood Flow ,Immunology ,Cancer research ,Bone marrow ,business - Abstract
Background The custom microenvironment ‘vascular niche’ is a potential therapeutic target for several pathophysiological conditions. Osteoblasts regulate the hematopoietic stem cell niche, and activation of the parathyroid hormone (PTH) receptor can increase the number of cells mobilized into the bloodstream. Methods C57Bl/6 mice were randomly assigned treatment with granulocyte-colony stimulating factor (G-CSF), PTH, G-CSF plus PTH or saline. All mice underwent hindlimb ischemia. Blood flow was measured by laser Doppler imaging. Indices of capillary activity were determined by electron microscopy in muscle tissue. CD34+ and Ki67+ cells were detected and evaluated by immunofluorescence, apoptosis by TUNEL, surface antigen and endothelial progenitor cells by fluorescence-activated cell sorting analysis, and vascular endothelial growth factor-164 and angiopoietin-1 expression by reverse-transcriptase polymerase chain reaction. Frozen bone marrow sections were stained for antigen-specific B cells and fibronectin and analyzed by confocal laser scanning microscopy. Results Following mobilization induced by G-CSF treatment, mice also treated with PTH showed increases in blood flow, capillary density, nitrite/nitrate release, angiogenic factors and circulating progenitor cells, as well as reduced apoptosis, fibrosis, oxidative stress and inflammation in ischemic muscles. Furthermore, hematopoietic antigen-specific B cells in the bone marrow were also increased by G-CSF alone and in combination with PTH. Conclusions PTH might increase the efficiency of hematopoietic stem-cell-based therapy in a recognized model of peripheral ischemia. Our translational experimental therapeutic targeting of the vascular niche points to novel clinical targets for the hematopoietic stem-cell treatment of ischemic vascular diseases.
- Published
- 2008
3. Therapeutic targeting of the stem cell niche in experimental hindlimb ischemia.
- Author
-
Napoli C, William-Ignarro S, Byrns R, Balestrieri ML, Crimi E, Farzati B, Mancini FP, de Nigris F, Matarazzo A, D'Amora M, Abbondanza C, Fiorito C, Giovane A, Florio A, Varricchio E, Palagiano A, Minucci PB, Tecce MF, Giordano A, Pavan A, and Ignarro LJ
- Subjects
- Angiopoietin-1 genetics, Angiopoietin-1 metabolism, Animals, Apoptosis drug effects, Blood Flow Velocity drug effects, Capillaries drug effects, Disease Models, Animal, Drug Therapy, Combination, Fibrosis, Filgrastim, Hematopoietic Stem Cells pathology, Hindlimb, Humans, Inflammation pathology, Inflammation prevention & control, Ischemia pathology, Ischemia physiopathology, Mice, Mice, Inbred C57BL, Muscle, Skeletal blood supply, Muscle, Skeletal pathology, Neovascularization, Physiologic drug effects, Oxidative Stress drug effects, RNA, Messenger metabolism, Rats, Recombinant Proteins, Regional Blood Flow drug effects, Time Factors, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Cell Movement drug effects, Granulocyte Colony-Stimulating Factor pharmacology, Hematopoietic Stem Cell Mobilization methods, Hematopoietic Stem Cells drug effects, Ischemia drug therapy, Muscle, Skeletal drug effects, Parathyroid Hormone pharmacology, Peptide Fragments pharmacology
- Abstract
Background: The custom microenvironment 'vascular niche' is a potential therapeutic target for several pathophysiological conditions. Osteoblasts regulate the hematopoietic stem cell niche, and activation of the parathyroid hormone (PTH) receptor can increase the number of cells mobilized into the bloodstream., Methods: C57Bl/6 mice were randomly assigned treatment with granulocyte-colony stimulating factor (G-CSF), PTH, G-CSF plus PTH or saline. All mice underwent hindlimb ischemia. Blood flow was measured by laser Doppler imaging. Indices of capillary activity were determined by electron microscopy in muscle tissue. CD34(+) and Ki67(+) cells were detected and evaluated by immunofluorescence, apoptosis by TUNEL, surface antigen and endothelial progenitor cells by fluorescence-activated cell sorting analysis, and vascular endothelial growth factor-164 and angiopoietin-1 expression by reverse-transcriptase polymerase chain reaction. Frozen bone marrow sections were stained for antigen-specific B cells and fibronectin and analyzed by confocal laser scanning microscopy., Results: Following mobilization induced by G-CSF treatment, mice also treated with PTH showed increases in blood flow, capillary density, nitrite/nitrate release, angiogenic factors and circulating progenitor cells, as well as reduced apoptosis, fibrosis, oxidative stress and inflammation in ischemic muscles. Furthermore, hematopoietic antigen-specific B cells in the bone marrow were also increased by G-CSF alone and in combination with PTH., Conclusions: PTH might increase the efficiency of hematopoietic stem-cell-based therapy in a recognized model of peripheral ischemia. Our translational experimental therapeutic targeting of the vascular niche points to novel clinical targets for the hematopoietic stem-cell treatment of ischemic vascular diseases.
- Published
- 2008
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