Evaluation of Mesenchymal Stem Cell-Based Therapies for Inflammatory Lung Diseases

• Author / Creator

  Ionescu, Lavinia Iuliana

• Recent discoveries in stem cell biology have generated enthusiasm about the possibility of harnessing stem cells for organ repair and regeneration. The ability of pluri- and multipotent stem cells to differentiate along various cellular lineages has placed them at the core of research that seeks to protect endogenous stem cell populations or to deliver exogenous stem cells to sites of organ injury. Lung diseases are a major health care concern and the prevalence of chronic lung diseases such as asthma, pulmonary fibrosis and chronic obstructive pulmonary disease is expected to continue to rise over the next decades. Meanwhile, improved perinatal care has allowed the survival of extremely premature infants that constitute a particularly vulnerable subpopulation because of their risk of developing bronchopulmonary dysplasia (BPD) with potential life-long complications. Research that aims to evaluate the therapeutic potential of exogenous stem cells in lung diseases placed an initial emphasis on the engraftment and differentiation of these cells in the lung. More recent studies demonstrate that multipotent stem cell populations, such as mesenchymal stromal cells (MSCs), exert paracrine activity that can modulate local inflammatory and immune responses in experimental lung disease models including asthma, acute lung injury (ALI) and pulmonary fibrosis. The studies presented hereby demonstrate that factors secreted by adult bone marrow-derived MSCs can prevent the development of inflammatory lung diseases in mouse models of asthma and ALI and provide mechanistic insight into the anti-inflammatory properties of MSCs. The perspective of using pluripotent stem cells as therapeutic agents has been revived by the landmark discovery of induced pluripotency, where “embryonic stem cell (ESC)-like” cells can be generated by reprogramming terminally differentiated somatic cells. While the field of induced pluripotent stem cell (iPSC) biology is still in its effervescent infancy, this finding may relieve many ESCs-related ethical concerns and may open the way to large-scale production and evaluation of pluripotent stem cells for organ regeneration and repair. The additional study presented provides proof-of-concept for the utility of iPSC. Together, the studies presented hereby advocate the potential of stem cells as a novel clinical option for the treatment of severe lung diseases.

• Subjects / Keywords

  • Mesenchymal stem cells
  • Acute lung injury
  • Lipopolysaccharide
  • Asthma
  • Ovalbumin
  • Lung

• Graduation date

  Fall 2012

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3N41H

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.