Effect of Periodic Granulocyte Colony‐Stimulating Factor Administration on Endothelial Progenitor Cells and Different Monocyte Subsets in Pediatric Patients with Muscular Dystrophies

Abstract

Muscular dystrophies (MD) are heterogeneous group of diseases characterized by progressive muscle dysfunction. There is a large body of evidence indicating that angiogenesis is impaired in muscles of MD patients. Therefore, induction of dystrophic muscle revascularization should become a novel approach aimed at diminishing the extent of myocyte damage. Recently, we and others demonstrated that administration of granulocyte colony-stimulating factor (G-CSF) resulted in clinical improvement of patients with neuromuscular disorders. To date, however, the exact mechanisms underlying these beneficial effects of G-CSF have not been fully understood. Here we used flow cytometry to quantitate numbers of CD34+ cells, endothelial progenitor cells, and different monocyte subsets in peripheral blood of pediatric MD patients treated with repetitive courses of G-CSF administration. We showed that repetitive cycles of G-CSF administration induced efficient mobilization of above-mentioned cells including cells with proangiogenic potential. These findings contribute to better understanding the beneficial clinical effects of G-CSF in pediatric MD patients.

Elevated Numbers of Circulating Very Small Embryonic-Like Stem Cells (VSELs) and Intermediate CD14++CD16+ Monocytes in IgA Nephropathy

“…Here, in our group of IgAN patients, we found significantly increased numbers of circulating intermediate CD14++CD16+ monocytes. Interestingly, intermediate CD14++CD16+ monocytes were shown, by our and other groups, to possess reparatory and proangiogenic potential [ 20 , 24 , 44 , 45 ]. In fact, these cells may produce high amounts of anti-inflammatory cytokines and represent predominant population of circulating pro-angiogenic (Tie-2 expressing) leukocytes [ 44 , 46 , 47 ].…”

“…600 μl (for VSELs and HSCs), 200 μl (for EPCs) and 100 μl (for monocytes) of fresh EDTA-anticoagulated whole blood was stained with a panel of monoclonal antibodies (mAbs; described in detail in Table 2 ) according to stain-then-lyse-then-wash protocol as described previously [ 20 , 22 , 23 ]. Briefly, samples were incubated in presence of mAbs for 30 min at room temperature in the dark.…”

“…In fact, several populations of mononuclear cells such as M2 macrophages and intermediate monocytes characterized by CD14++CD16+ phenotype can support stem cells in some regenerative actions, mostly those related to reconstruction of injured vessels [ 18 , 19 ]. These mononuclear cells were shown to support regeneration process mostly by regulation of angiogenesis and the release of several growth factors [ 18 , 20 , 21 ]. To date, however, our understanding of the mechanisms of renal regeneration in humans remains limited.…”

Efficacy and the Safety of Granulocyte Colony-Stimulating Factor Treatment in Patients with Muscular Dystrophy: A Non-Randomized Clinical Trial

“…This population is able to support muscle cell regeneration by including satellite cell proliferation and tissue revascularization ( 22 ). To find exact mechanisms underlying beneficial effects of G-CSF in patients with neuromuscular disorders, Eljaszewicz et al ( 18 ) used flow cytometry to quantitate numbers of CD34+ cells, endothelial progenitor cells, and different monocyte subsets in the peripheral blood of the patients treated with repetitive courses of G-CSF administration. The observed effect was an inducement of efficient mobilization of the abovementioned cells, including cells with proangiogenic potential.…”

“…Blood was collected before G-CSF administration and on the fifth day of each treatment cycle. The assessment of hematopoietic stem/progenitor cells (CD34+), endothelial progenitor cells (CD34+ CD133+ CD309), monocyte subsets (CD14, CD16) was performed using flow cytometry in 11 patients in previous study ( 18 ).…”