Bone marrow mononuclear cell therapy in experimental allergic asthma: Intratracheal versus intravenous administration

Abstract

We hypothesized that the route of administration would impact the beneficial effects of bone marrow-derived mononuclear cell (BMDMC) therapy on the remodelling process of asthma. C57BL/6 mice were randomly assigned to two main groups. In the OVA group, mice were sensitized and challenged with ovalbumin, while the control group received saline using the same protocol. Twenty-four hours before the first challenge, control and OVA animals were further randomized into three subgroups to receive saline (SAL), BMDMCs intravenously (2×10(6)), or BMDMCs intratracheally (2×10(6)). The following changes were induced by BMDMC therapy in OVA mice regardless of administration route: reduction in resistive and viscoelastic pressures, static elastance, eosinophil infiltration, collagen fibre content in airways and lung parenchyma; and reduction in the levels of interleukin (IL)-4, IL-13, transforming growth factor-β and vascular endothelial growth factor. In conclusion, BMDMC modulated inflammatory and remodelling processes regardless of administration route in this experimental model of allergic asthma.

Stem cells in animal asthma models: a systematic review

“…Of these, 30 studies were selected for full text review, 19 of which met the inclusion criteria. Two studies were excluded because bone marrowederived mononuclear cells were used rather than stem cells [7,8] because soluble factors from bone marrow cells were used [5].…”

“…In fact, Abreu et al [7,8] have shown that bone marrow mononuclear cell administration before allergen challenge also reduced eosinophilic infiltration, Th2 cytokines, airway remodeling and airway hyperresponsiveness whether injected intravenously or intratracheally. With the use of MSCs treated with a cross-linker to prevent release of soluble factors, Goodwin et al [20] demonstrated that the effects of MSCs were not due to surface antigens either, but to soluble factors.…”

“…Other concerns may include clumping of the stem cells in the pulmonary vasculature when administered intravenously and the introduction of foreign antigens present in culture media. We note that intratracheal administration is feasible because it was used successfully in a few studies [8,11,23,24]. MSC treatment has been evaluated in human clinical trials for several other conditions including acute myocardial infarction [36], stroke, diabetes and multiple sclerosis [37] and for cartilage repair [38], with no particular safety concerns emerging, including tumors.…”

The Effects of Short-Term Propofol and Dexmedetomidine on Lung Mechanics, Histology, and Biological Markers in Experimental Obesity

“…Because the NI of the lines with the epithelial basal membrane is proportional to the airway area, the magnitude of bronchoconstriction (contraction index) was computed as contraction index = NI/√NP. 22 Lung morphometric analysis was performed in a blinded fashion.…”

An Official American Thoracic Society Workshop Report: Stem Cells and Cell Therapies in Lung Biology and Diseases

“…In the ovalbumin asthma model, murine bone marrow-derived mononuclear cells, which were isolated using gradient centrifugation and administered intravenously, attenuated eosinophilic inflammation, airway remodelling, and physiologic parameters (105). These effects were independent of the route of administration (intravenous or intratracheal) (106). Next, her group compared their bone marrow-derived mononuclear cells to murine bone marrow-derived MSCs.…”