Dr. Mauricio Rojas’ Research
The focus of Dr. Rojas’ research is finding the role of Mesenchymal Stem Cells in lung repair after injury. The models standardized in his lab include:
a) Bleomycin induced pulmonary fibrosis, where it was found that myelosupression increased susceptibility to injury and that stem cell transfer was protective. These transferred cells can detect the injured lung and assume lung cell phenotypes, but having protection from injury and fibrosis requires suppression of inflammation and triggering production of reparative growth factors.
b) A second model of lung injury that was established is the ventilator induced-mechanical injury. A selective ventilator designed to ventilate each lung independently was utilized. One notable advantage of this model for studying is that biological variability between animals is reduced since the same animal is used as test and control. This purpose of this model is to study the use of mesenchymal stem cells to prevent this common type of injury in assisted ventilated patients.
c) A third model is the post radiation lung injury. For this model, the hypothesis is that that the chemokine SDF-1 is induced in the lung in response to radiation injury leading to the recruitment of bone marrow-derived CXCR4-expressing fibroblast progenitor cells called “fibrocytes” to the site of pulmonary injury. It is believed that recruitment of these bone marrow cells is a critical step for the development of radiation-induced pulmonary fibrosis and that disruption of the SDF-1:CXCR4 signaling axis may prevent the development of this potentially devastating pulmonary complication. Testing is being done on the CXCR4 antagonist WZ40 as a potential mitigator for the development lung fibrosis after exposure to radiation. Dr. Rojas’ lab hypothesizes that blockade of the SDF-1:CXCR4 axis with this drug during the time of injury may be sufficient to halt recruitment of the fibrocytes and hold the fibrotic process.
d) A fourth model, work in acute lung injury induced by systemic administration of endotoxin, in which we were pioneers describing the anti-inflammatory effect of the Mesenchymal Stem Cells in the lung repair, a well accepted concept in the scientific community today. It has been demonstrated that mesenchymal stem cells decrease both the systemic and local inflammatory responses induced by endotoxin. These effects do not require either lung engraftment or differentiation of the stem cells and are due at least in part to the production of stem cell chemoattractants by the lungs and to humoral and physical interactions between stem cells and lung cells.
e) Finally, lung transplant is the last and unique alternative for patients with a variety of lung diseases. Unfortunately, survival in lung transplant remains low compare to transplants of other organs. The main complication is the Bronchiolitis obliterans (BO) which is an occlusion of the airways by deposition of collagen and fibrin in the lumen of the airway. Dr. Rojas’ lab continues to conduct evaluation of the use of mesenchymal stem cells to prevent the development of BO. In the mouse model of heterotopic trachea transplantation, it was possible to prevent the occlusion of the airways by infusing Mesenchymal Stem Cells into the recipient of an allogenic transplant. Recently the lab initiated a new area of research in aging, to determine the effect of aging in the recruitment of stem cells into the injured organ and the ability of senescent stem cells to respond to the different signals involved in recruitment and differentiation of these cells.
Dr. Rojas’ immediate goal is to expand the understanding of the immune and cellular mechanisms used by mesenchymal stem cells to prevent lung injury, and the regulation of their migration and recruitment to the injury site. Specifically, studying the effect of Mesenchymal Stem Cells in the differentiation of T regulatory cells and TGF-b signaling and the mechanisms of recruitment of endogenous stem cells using the parabiosis animal model. This will allow the designation of better clinical trials according to the type of injury that is suffering the lung. By translating this knowledge into clinic Dr. Rojas hopes to complete his long term goal: better conditions of life on patients with lung diseases.