(W1246) CONTINUAL COLLECTION OF CONDITIONED MEDIUM FROM QUIESCENT ADIPOSE TISSUE-DERIVED STROMAL CELLS EMBEDDED IN GELS TO SUPPLY MATERIALS TO ENHANCE WOUND HEALING IN DIABETIC MICE
Director/Designated Professor TOKUSHIMA UNIVERSITY Tokushima, Tokushima, Japan
Abstract: Mesenchymal stem cell (MSC)-based cell therapies for diabetic ulcers have attracted much attention, but have not become widespread. One of the reasons for this is that chronic inflammation in diabetes causes premature senescence of MSC, which significantly impairs their proliferative and differentiation potential as well as their immunomodulatory functions. We have previously reported that quiescence of adipose tissue-derived stromal cells (ADSC), one type of MSC that has been utilized to develop MSC-based cell therapies, induced by culturing them in three-dimensional gels with the stiffness of adipose tissue, eliminates premature senescence of ADSC caused by high-glucose treatment. We have also reported that transplanting quiescent ADSC in gels promotes wound healing in diabetic mice. In this study, we investigated the effect administering conditioned medium derived from quiescent ADSC (Q-CM) on diabetic ulcers and attempted to construct a highly efficient method to produce Q-CM for future clinical application. To this end, Q-CM was collected every 3 days from the same quiescent ADSC in gels and used to culture cells seeded on plastic culture plates or intradermally injected into streptozotocin-induced diabetic mice (STZ mice) after removal of skin on their back. Compared to regular culture medium, fibroblast migration and tube formation by vascular endothelial cells were enhanced, when Q-CM was administered. A cohort of Q-CM exhibited a similar level of restoration of proliferation and tumor necrosis factor-alpha/interferon-gamma-stimulated indolamine 2,3-deoxygenase secretion by aged ADSC. Q-CM also accelerated wound healing in STZ mice. These results suggest that it is possible to continually collect CM from quiescent ADSC with maintained therapeutic effects on diabetic wound healing.
