Melbourne, Australia -
Systemic administration of stem cells is usually associated with preferential localization into the lung and liver. Lung conditions such as acute respiratory distress syndrome have no cure with exception of transplantation, which is limited to a small number of patients. The rationale of using mesenchymal stem cells for pulmonary diseases comes from their ability to inhibit fibrosis, which has been previously reported in liver failure, their ability to differentiate into pulmonary cells, and their capacity to produce growth factors. Additionally, bone marrow mononuclear cells, which are known to contain both hematopoietic and mesenchymal stem cells have been previously demonstrated to effectively treat an animal model of pulmonary hypertension.
In a recent study (Moodley et al. Human Umbilical Cord Mesenchymal Stem Cells Reduce Fibrosis of Bleomycin-Induced Lung Injury. Am J Pathol, 2009 Jun 4) the therapeutic ability of Wharton's Jelly derived mesenchymal stem cells was assessed in a lung fibrosis model.
The investigators intravenously administered the mesenchymal stem cells and induced lung injury using the fibrosis-inducing agent bleomycin. The human mesenchymal stem cells were only detected in areas of injured lungs but not in alveolar tissue that was not damaged.
Suppression of TGF-beta, IFN-gamma, TNF-alpha, and macrophage chemoattractants was observed locally in the animals treated with the mesenchymal stem cells.
Expression of the TGF-beta effector transcription factor SMAD-2 was also suppressed by the mesenchymal stem cell treatment, whereas matrix metalloprotease 2, which is involved in clearing of fibrotic tissue was upregulated.
The current study supports the possibility of using systemic administration of mesenchymal stem cells for treatment of various fibrotic conditions, however efficacy appears to still require optimization. Hypothetically one could do this by co-administration of mesenchymal stem cells with agents capable of in vivo activating the cells, for example, estrogen.