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Abstract
FDA-approved mesenchymal stem cell (MSC) clinical therapies have been elusive despite strong evidence of their potential to modulate immune response in preclinical models. This failure stems in part from the loss of immune modulatory activity after the high degree of expansion required to make an adequate dose of MSCs for clinical use, and an inability to monitor MSC immune modulatory potential during the expansion process.
Studies show that indoleamine-2,3-dioxygenase (IDO), which is the first and rate-limiting enzyme that catabolizes tryptophan (a promoter of T-cell activity) into L-kynurenine, can be considered as a critical factor during MSCs suppression of T-cell proliferation.
Therefore, here we investigate MSC immune potency through IDO activity and expression as well as the relationship to MSC morphology, proliferation, and senescence. Our work focuses on the following: 1) the change in IDO activity over passages with a concurrent change in cell proliferation rate; 2) the potential of a correlation between IDO expression and cell morphology; 3) using a morphological imaging approach to separate high IDO potency and high proliferation MSCs during culture expansion.
The success of our future work could provide key insights into potency metrics that would allow for monitoring and selection of high immune potency MSCs. This would significantly increase the efficacy of MSC therapies and provide much-needed relief to patients suffering with immune diseases.
Studies show that indoleamine-2,3-dioxygenase (IDO), which is the first and rate-limiting enzyme that catabolizes tryptophan (a promoter of T-cell activity) into L-kynurenine, can be considered as a critical factor during MSCs suppression of T-cell proliferation.
Therefore, here we investigate MSC immune potency through IDO activity and expression as well as the relationship to MSC morphology, proliferation, and senescence. Our work focuses on the following: 1) the change in IDO activity over passages with a concurrent change in cell proliferation rate; 2) the potential of a correlation between IDO expression and cell morphology; 3) using a morphological imaging approach to separate high IDO potency and high proliferation MSCs during culture expansion.
The success of our future work could provide key insights into potency metrics that would allow for monitoring and selection of high immune potency MSCs. This would significantly increase the efficacy of MSC therapies and provide much-needed relief to patients suffering with immune diseases.