Properties of Mesenchymal Stem Cells in Lung Transplant

Problem of Interest: Lung transplantation represents a potential therapy for patients with
end-stage lung diseases such as pulmonary fibrosis, emphysema and cystic fibrosis. The major
limitation to long term survival in lung transplant recipients is the development of graft
failure over time, termed bronchiolitis obliterans. The conventional therapies used to
prevent rejection are not effective in preventing bronchiolitis obliterans. Therefore, new
therapies are needed to address this problem. A growing body of research has focused on a
unique population of bone marrow cells termed Mesenchymal Stem Cells (MSCs) to improve a
range of medical conditions including heart failure, autoimmune disease, and inflammatory
bowel disease. MSCs can prevent animal models of bronchiolitis obliterans. Because of this
information, it is plausible that MSCs could help patients as a potential treatment in lung
transplantation. MSCs can be obtained from 2 sources: commercially available MSCs which are
generated from other normal volunteers and from the patient themselves. When MSCs are
obtained from the patient for whom they are used, they are termed "autologous MSCs". A major
potential drawback to the use of commercially available MSCs is that these cells contain
proteins from other individuals which could provoke rejection when used in lung transplant
recipients. Therefore, the use of autologous MSCs currently appears the most attractive
option. What is not understood at the present time is the extent to which autologous MSCs
obtained from chronically ill patients with end-stage lung disease still maintain properties
which would be beneficial. This proposal will test the immunologic properties of MSCs
generated from such individuals to answer the question of whether generation of whether it
would be feasible to use such cells in the future to prevent entities such as bronchiolitis
obliterans.

Overview on how this will be studied: The Investigator will approach patients who are being
considered for a lung transplant because of end stage lung disease. Enrolled patients will
undergo a bone marrow aspiration where a small amount of fluid is removed from their pelvic
bone. Cells obtained in this procedure will be expanded in the Emory/Georgia Tech Cell Lab.
MSCs will be expanded in this lab using cell culture conditions which are standardly used
for MSCs. The Investigator will test the efficiency of expansion of these MSCs to determine
if they can be obtained from all patients, or if there some patients demonstrate inefficient
MSC expansion based on age or disease or other factors. The Investigator will then test
in-vitro the ability of MSCs from different patients to prevent activation of the immune
system when faced with proteins from other individuals. The Investigator believes this model
system approximates the type of interaction that would occur if these MSCs were given to
patients who received a lung transplant.

Benefit of research to knowledge and human health: It is not presently known whether
patients with severe medical illness are able to have MSCs expanded. If it is found that
MSCs can be readily obtained from such individuals and additionally find that such MSCs have
properties which would be predicted to be beneficial in lung transplant, this study would
provide the rationale to use MSCs as a therapeutic agent in patients undergoing lung
transplantation.

Inclusion Criteria:

- Patients aged 18-70 without regard to race or gender

- End stage lung disease from IPF, cystic fibrosis, emphysema, sarcoidosis or pulmonary
hypertension

- Expected time from enrollment to transplant greater than 4 weeks

- Patient willing to undergo a bone marrow aspiration prior to transplantation

Exclusion Criteria:

- Patients under age 18

- Patients on significant immunosuppressive agents prior to transplant (specifically
calcineurin inhibitors, cell cycle inhibitors or prednisone >0.5 mg/kg lean body
weight)