Properties of Mesenchymal Stem Cells in Lung Transplant

Lung Transplantation Clinical Trial

Official title:

Properties of Mesenchymal Stem Cells in Lung Transplant Candidates

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01668576
• Other study ID #: IRB00053075
• Status: Terminated
• Phase: N/A
• First received: August 15, 2012
• Last updated: January 13, 2016
• Start date: August 2012
• Est. completion date: September 2014

Study information

• Verified date: January 2016
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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)

Study Design

Observational Model: Cohort, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Lung Transplantation

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intrinsic variability of MSCs measured by time to third passage of confluent MSC	Assess for intrinsic variability of MSCs derived from individuals with end-stage lung disease across a range of ages, disease types, and comorbid conditions	Post Co-Culture (24 hours)	No
Primary	2-3 IDO production measured as ug/mL of passage 3 MSCs	Demonstrate autologous MSCs have in-vitro immunoregulatory properties against allo-specific T cell responses and compare the MSC effects to conditioned media from MSCs	Post Co-Culture (24 hours)	No
Primary	Percent specific inhibition of CD4 and CD8 T cell proliferation toward donor target cells in one way mixed-lymphocyte reactions	Test the immunoregulatory properties of MSCs in the setting of conventional levels of immune suppression	Post Co-Culture (24 hours)	No