According to the Wound Healing Society, about 15% of older adults in the United States suffer from chronic, hard-to-heal skin wounds. An increase in proteolytic activity is associated with intrinsic cutaneous aging predisposing the elderly to tissue breakdown. Furthermore, chronic wounds inherently exhibit a highly proteolytic environment resulting in abnormal degradation of the extracellular matrix, critical soluble or matrix-associated growth factors, and their respective cellular receptors. Therefore, the proteolytic nature of aged skin not only contributes to impaired acute wound healing, but perpetuates existing chronic cutaneous wounds in older adults. Strategies to attenuate the highly proteolytic environment of chronic wounds have the potential to dramatically enhance the healing of these hard-to-heal wounds. To date no biological treatment options specifically targeting the proteolytic nature of chronic wounds have been developed and marketed. In this Phase I feasibility determination, we propose to generate and characterize a human keratinocyte cell line genetically-modified to constitutively express a functional, bioactive proteinase inhibitor. This cellular reagent is intended for eventual use in ExpressGraft(tm)shieid, a cell-based gene therapy product engineered to combat the excess proteolytic activity associated with chronic cutaneous wounds in the elderly. Advances in ex vivo genetic engineering of a patented human keratinocyte cell line at Stratatech Corporation has made it uniquely positioned to complete this work. Upon successful completion of Phase I objectives, we will expand our studies to examine tissue generated from candidate cellular reagents both in vitro and in vivo during subsequent Phase II preclinical testing.
| De Abrew, K Nadira; Thomas-Virnig, Christina L; Rasmussen, Cathy A et al. (2014) TCDD induces dermal accumulation of keratinocyte-derived matrix metalloproteinase-10 in an organotypic model of human skin. Toxicol Appl Pharmacol 276:171-8 |
