Granulocyte-Colony Stimulating Factor for Mobilizing Bone Marrow Stem Cells in Subacute Stroke

Abstract

Background and Purpose-Granulocyte-colony stimulating factor (G-CSF) is neuroprotective in experimental stroke and mobilizes CD34 ϩ peripheral blood stem cells into the circulation. We assessed the safety of G-CSF in recent stroke in a phase IIb single-center randomized, controlled trial. Methods-G-CSF (10 g/kg) or placebo (ratio 2:1) was given SC for 5 days to 60 patients 3 to 30 days after ischemic or hemorrhagic stroke. The primary outcome was the frequency of serious adverse events. Peripheral blood counts, CD34 ϩ count, and functional outcome were measured. MRI assessed lesion volume, atrophy, and the presence of iron-labeled CD34 ϩ cells reinjected on day 6. Results-Sixty patients were recruited at mean of 8 days (SD Ϯ5) post ictus, with mean age 71 years (Ϯ12 years) and 53% men. The groups were well matched for baseline minimization/prognostic factors. There were no significant differences between groups in the number of participants with serious adverse events: G-CSF 15 (37.5%) of 40 versus placebo 7 (35%) of 20, death or dependency (modified Rankin Score: G-CSF 3.3Ϯ1.3, placebo 3.0Ϯ1.3) at 90 days, or the number of injections received. G-CSF increased CD34 ϩ and total white cell counts of 9.5-and 4.2-fold, respectively. There was a trend toward reduction in MRI ischemic lesion volume with respect to change from baseline in G-CSF-treated patients (Pϭ0.06). In 1 participant, there was suggestion that labeled CD34 ϩ cells had migrated to the ischemic lesion. Conclusions-This

G-CSF as an Adjunctive Therapy with Umbilical Cord Blood Cell Transplantation for Traumatic Brain Injury

“…Previous studies found that G-CSF-mobilized stem cells infiltrate injured tissues to promote neural repair (28,88,104). As mentioned above, G-CSF displayed capacity to cross the BBB to act upon neurons and glial cells through the G-CSF receptor (134), of which their activation has been demonstrated to downregulate expression of proinflammatory cytokines and to enhance neurogenesis (95,115).…”

“…Currently, a limited clinical trial is under way for testing G-CSF in TBI patients (personal communication with Dr. Juan SanchezRamos, USF/VA). Despite inconsistent efficacy results, the translation of G-CSF for TBI in the clinic is based on the drug's safety profiles for its indication in acute ischemic stroke and AD (28,87,88,103,104).…”

Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review

“…[12][13][14]20,22,24,31,32,65,[66][67][68][69][70][71]74 In addition to dextran, seven other types of SPION coatings were identified, such as starch, phosphatidylcholine, DEAE-diphosphate starch and poly-diallyl-dimethylamine in the Riegler et al 72 study; carboxylated iron oxide core was seen in the Detante et al 64 study, silica in the study by Wang et al 63 monomer citrate in the study by Stroh et al 23 and DPPA in the study by Bjorklund et al 19 There was one study 62 that used both dextran and chitosan.…”

“…Regarding the analysis of the SPION cell labeling process by the 32 selected articles, the majority (19) used mesenchymal stem cells (MSC), six articles 12,19,23,33,66,74 used embryonic stem cells, five articles 20,25,30,70,76 used neural stem cells, one article 65 used hematopoietic stem cells, and the other article 31 used amniotic fluid-derived stem cells ( Table 2). The use of a transfection agent and a culture medium to optimize the stem cell labeling process with SPION is usual.…”

“…72 A total of six studies did not specify medium. 14,15,63,65,68,73 Again analyzing the process of SPION stem cell labeling, most studies used a transfection agent for particle internalization. 12,14,62,[67][68][69]73,74 Among those, six studies 12,14,62,67,69,73 used PLL, one study 74 used FuGENE ® (Promega Corporation, Fitchburg, WI, USA) and one study 68 used protamine sulfate.…”