Metabolomics and cytokine profiling of mesenchymal stromal cells identify markers predictive of T-cell suppression |
| |
| Institution: | 1. School of Chemical, Materials, and Biomedical Engineering, University of Georgia, Athens, Georgia, USA;2. Regenerative Bioscience Center, University of Georgia, Athens, Georgia, USA;3. Complex Carbohydrate Research Center and Institute of Bioinformatics, University of Georgia, Athens, Georgia, USA;4. School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, USA;5. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA;6. Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA;7. Department of Animal and Dairy Sciences, University of Georgia, Athens, Georgia, USA;1. The State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China;2. Department of Central Lab, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China;1. Air Force Medical Center, People''s Liberation Army, Beijing, People''s Republic of China;2. Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, People''s Republic of China;3. Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People''s Republic of China;4. Beijing Institute of Basic Medical Sciences, Beijing, People''s Republic of China;5. The Fifth Medical Center of Chinese People''s Liberation Army General Hospital, Beijing, People''s Republic of China;6. Graduate School of Anhui Medical University, Hefei, People''s Republic of China;1. Division of Hematology, Center of Cellular Therapy “G. Lanzani,” Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy;2. Centre National de la Recherche Scientifique UAR3426 “Baculovirus et Thérapie,” Saint-Christol-Lez Alès, France;3. Accelera srl, Nerviano, Italy;4. Nerviano Medical Sciences, Nerviano, Italy;5. Fondazione per la Ricerca Ospedale Maggiore, Bergamo, Italy;1. Cancer and Blood Disease Institute, Children''s Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California, USA;2. Center for Cancer and Blood Disorders, Children''s National Hospital, George Washington School of Medicine, Washington, DC, USA;3. Department of Immunology and Microbiology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, USA;4. Seattle Children''s Therapeutics, Seattle Children''s Research Institute, Seattle, Washington, USA;1. Institute of Computer Sciences, Foundation for Research and Technology Hellas, Heraklion, Greece;2. Public Cord Blood Bank of Crete, Department of Hematology, University Hospital of Heraklion, Heraklion, Greece;3. Haemopoiesis Research Laboratory, School of Medicine, University of Crete, Heraklion, Greece;4. CeMIA SA, Larissa, Greece;1. Department of Intensive Care Medicine, The Third Xiangya Hospital of Central South University, Changsha, China;2. Department of Preparations, The First Hospital of Hunan University of Chinese Medicine, Changsha, China |
| |
| Abstract: | Background aimsMesenchymal stromal cells (MSCs) have shown great promise in the field of regenerative medicine, as many studies have shown that MSCs possess immunomodulatory function. Despite this promise, no MSC therapies have been licensed by the Food and Drug Administration. This lack of successful clinical translation is due in part to MSC heterogeneity and a lack of critical quality attributes. Although MSC indoleamine 2,3-dioxygnease (IDO) activity has been shown to correlate with MSC function, multiple predictive markers may be needed to better predict MSC function.MethodsThree MSC lines (two bone marrow-derived, one induced pluripotent stem cell-derived) were expanded to three passages. At the time of harvest for each passage, cell pellets were collected for nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography mass spectrometry (MS), and media were collected for cytokine profiling. Harvested cells were also cryopreserved for assessing function using T-cell proliferation and IDO activity assays. Linear regression was performed on functional data against NMR, MS and cytokines to reduce the number of important features, and partial least squares regression (PLSR) was used to obtain predictive markers of T-cell suppression based on variable importance in projection scores.ResultsSignificant functional heterogeneity (in terms of T-cell suppression and IDO activity) was observed between the three MSC lines, as were donor-dependent differences based on passage. Omics characterization revealed distinct differences between cell lines using principal component analysis. Cell lines separated along principal component one based on tissue source (bone marrow-derived versus induced pluripotent stem cell-derived) for NMR, MS and cytokine profiles. PLSR modeling of important features predicted MSC functional capacity with NMR (R2 = 0.86), MS (R2 = 0.83), cytokines (R2 = 0.70) and a combination of all features (R2 = 0.88).ConclusionsThe work described here provides a platform for identifying markers for predicting MSC functional capacity using PLSR modeling that could be used as release criteria and guide future manufacturing strategies for MSCs and other cell therapies. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
