Bone marrow mesenchymal stem cells can be mobilized into peripheral blood by G-CSF in vivo and integrate into traumatically injured cerebral tissue

Abstract

The efficacy of granulocyte colony-stimulating factor (G-CSF) in mobilizing mesenchymal stem cells (MSCs) into peripheral blood (PB) and the ability of PB-MSCs incorporated into injured brain were tested. Colony forming, cell phenotype and differentiation potential of mouse MSCs mobilized by G-CSF (40 μg/kg) were evaluated. Mortality and pathological changes in mice with serious craniocerebral trauma plus G-CSF treatment (40 μg/kg) were investigated. Bone marrow (BM) cells derived from GFP mice were fractionated into MSCs, hematopoietic stem cells (HSCs), and non-MSC/HSCs using magnetic beads and adherent culture. The resultant cell populations were transplanted into injured mice. The in vivo integration and differentiation of the transplanted cells were detected immunocytochemically. The expression of SDF-1 in injured area of brain was tested by Western blot. G-CSF was able to mobilize MSCs into PB (fourfold increase). PB-MSCs possessed similar characteristics as BM-MSCs in terms of colony formation, the expression pattern of CD73, 44, 90, 106, 31 and 45, and multipotential of differentiation. Accumulative total mice mortality was lower in TG group (5/14) than that in T group (7/14). It was MSCs, not HSCs or non-MSC/HSC cells integrated into the damaged cerebral tissue and differentiated into cells expressing neural markers. Increased SDF-1 expression in injured area of brain was confirmed, which could facilitate the homing of MSCs to brain. G-CSF can mobilize MSCs into PB and MSCs in PB can integrate into injured cerebral tissue and transdifferentiated into neural cells and may benefit the repair of trauma.

Neurotherapeutic Effect of Cord Blood Derived CD45+Hematopoietic Cells in Mice after Traumatic Brain Injury

“…Our finding of rapid homing of intravenously-administered HUCB-derived MNCs and CD45 + cells to the injured site is in line with previous reports tracking the integration of bone marrowderived MSCs into traumatic injured brain. 48,49 The decrease in brain NIR fluorescence of CHI mice treated with labeled MNCs cells at later time points post-administration, from 5 h to seven days (Fig. 6D) may indicate a very short-term retention of labeled cells at the injured site.…”

Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects

“…The release of brain-derived neurotrophic factor from transplanted hNSCs has been shown to provide some cognitive benefits in a mouse model of Alzheimer Disease (18). Moreover, bone marrow-derived stem cells may provide vascular support and help maintain the specialized vascular niche for stem cell maintenance (54,91,150,195,220). They can be recruited directly to the site of radiation injury in the brain, where they appear to provide support to the microvasculature (28).…”

Treatment of a mouse model of collagen antibody-induced arthritis with human adipose-derived secretions

“…G-CSF has classically been used to stimulate mobilization of hematopoietic stem cells from the bone marrow into the circulation. More recently, mobilization of MSCs from the bone marrow has been demonstrated following administration of G-CSF [38]. Therefore, it is possible that following administration of the therapeutics used in this study, the high levels of G-CSF stimulated mobilization of some MSCs from the bone marrow, which may have contributed to the therapeutic outcome observed.…”