Properties of Mesenchymal Stem Cells in Lung Transplant

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Emory University
Sponsor:
Information provided by (Responsible Party):
David C Neujahr, MD, Emory University
ClinicalTrials.gov Identifier:
NCT01668576
First received: August 15, 2012
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

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.

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.

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.


Condition
Lung Transplantation

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Properties of Mesenchymal Stem Cells in Lung Transplant Candidates

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Intrinsic variability of MSCs measured by time to third passage of confluent MSC [ Designated as safety issue: No ]
    Assess for intrinsic variability of MSCs derived from individuals with end-stage lung disease across a range of ages, disease types, and comorbid conditions

  • 2-3 IDO production measured as ug/mL of passage 3 MSCs [ Designated as safety issue: No ]
    Demonstrate autologous MSCs have in-vitro immunoregulatory properties against allo-specific T cell responses and compare the MSC effects to conditioned media from MSCs

  • Percent specific inhibition of CD4 and CD8 T cell proliferation toward donor target cells in one way mixed-lymphocyte reactions [ Designated as safety issue: No ]
    Test the immunoregulatory properties of MSCs in the setting of conventional levels of immune suppression


Biospecimen Retention:   Samples With DNA

mesenchymal stem cells derived from subject bone marrow aspiration


Estimated Enrollment: 20
Study Start Date: August 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Lung transplant candidates

Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01668576

Contacts
Contact: David Neujahr, MD 404-727-5854 dneujah@emory.edu
Contact: Beth Begley, RN 404-712-7168 beth.begley@emoryhealthcare.org

Locations
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: David Neujahr, MD    404-727-9651    dneujah@emory.edu   
Contact: Beth Begley, RN    404-712-7168    beth.begley@emoryhealthcare.org   
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: David Neujahr, MD Emory University
  More Information

No publications provided

Responsible Party: David C Neujahr, MD, Assistant Professor, Emory University
ClinicalTrials.gov Identifier: NCT01668576     History of Changes
Other Study ID Numbers: IRB00053075
Study First Received: August 15, 2012
Last Updated: July 31, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
mesenchymal stem cells
Lung transplantation

ClinicalTrials.gov processed this record on September 18, 2014