Wound Healing of Chronic Leg Ulcers Is Stimulated by Wound Edge Continuity with Adult Cultured Epidermal Autografts

Submit Manuscript | http://medcraveonline.com this definition has been met by our methods of isolation and cloning of adult epidermal keratinocytes, which exhibit a multigenerational proliferative life span and undergo parasynchronous terminal squamous differentiation under defined serum-free culture conditions [2]. At present, the best source of safe and reliable epithelial stem cells are autologous adult epidermal keratinocytes re-engineered as a biological dressing, a cultured epidermal autograft (CEA), useable for treatment of chronic wounds. The term biological dressings refers to the field of biomedical research and practice that focuses on the use of cell culture-derived tissue constructs to replace, restore and regenerate tissue loss due to damaged or diseased tissue cells. Biological dressings have had an important impact on outcome and efficacy of wound healing, and on the design and choice of the best clinical pathways for treatment of burns and other hardto-heal wounds [3,4]. To date, tissue engineered bilayered skin composite skin grafts using allogeneic keratinocytes have show only marginal wound healing benefit relative to standard of care treatment [5-11]. Use of allogeneic epidermal cells requires pooling of neonatal keratinocytes from many different human sources from cell bank stocks. This carries many serious safety and health concerns including immunological rejection, and the possibility of disease transmission from unscreened pathogenic bacteria and viruses. To prevent such consequences, costly screening and quality control tracking systems are required reducing the commercial potential of such products. Moreover, allogeneic epidermal keratinocytes transplanted to host wounds are only of transient benefit and are not permanently integrated in to the hosts healed tissue [12]. Recently, an innovative technique of cell therapy in which allogeneic keratinocytes and fibroblasts are sprayed on to debrided chronic leg ulcers wounds also showed only slight improvement in the rate or time to complete wound closure over and above compression therapy, the standard of care [13], and in a 24-week follow up, wound closure occurred for 43% of patients receiving cells versus 35% for those receiving vehicle [14]. Previously, we reported [15] using adult epidermal cells obtained from normal adult skin to treat chronic venous leg ulcers. The techniques and methods used to construct an autologous biological dressing composed entirely of autologous epidermal keratinocytes has been recently described [16]. The methodology differs substantially from both previous biological dressings composed of allogeneic epidermal keratinocyte and also from biological dressings composed of autologous epidermal keratinocytes [17-21], including the use of serumfree culture medium, absence of an organotypic matrix or xenobiotic such as cholera toxins, and irradiated mouse feeder layer cells. These improvements were employed before [2] to construct a serumfree adult CEA to heal chronic venous stasis leg ulcer. Here, we have evaluated our previous clinical data seeking correlations among a number of variables, including: