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Abstract: Bilayered living-cell therapy has been shown in clinical trials to improve the rate of healing diabetic and venous leg ulcerations. However, literature is conflicted regarding the length of time living-cell therapy persists in acute and chronic wounds. An otherwise healthy 48-year-old man with sepsis from extensive lower-extremity wounds due to ecthyma gangrenosum was admitted to the hospital. Initial treatment consisted of surgical debridement, broad-spectrum antibiotics, and stabilization in the intensive care unit. After the patient was stabilized, three units of living-cell therapy meshed at a 3:1 ratio were applied to the wounds. Both wounds were healed after 20 weeks. Ten months post grafting, the patient returned with a recurrent ulcer in the area of graft placement. A biopsy of the wound for human leukocyte antigen revealed the presence of donor DNA from the bilayered living-cell therapy. This case suggests that bilayered living-cell therapy may persist for prolonged periods in patients without underlying skin disease or immunosuppression. Research to explicate the mode of action and optimal protocols for use of living-cell therapy is warranted.

Key Words: skin graft, living-cell therapy, acute wound, viability, immunosuppression

Potential Conflicts of Interest: Dr. Serena discloses he has received speaker honoraria from and served as a consultant or paid advisory board member for Organogenesis, Canton, MA. Dr. Bialas has nothing to disclose.

Please address correspondence to: Thomas Serena, MD, FACS, Penn North Centers for Advanced Wound Care, 552 Quaker Hill Rd, Warren, PA 16365; email: serena@healingwounds.com.

     Bilayered, living-skin, cell therapy (Apligraf®, Organogenesis, Canton, MA) is composed of human epidermal keratinocytes, human dermal fibroblasts, and an extracellular matrix of bovine collagen. The keratinocytes and fibroblasts are derived from human neonatal foreskin. This bilayered living-cell therapy does not contain antigenic cells such as Langerhans cells, melanocytes, macrophages, lymphocytes, blood vessels, or hair follicles and there is no evidence of an immune response to the cellular components of this cell therapy on immunologic testing.^1,2

     In multicenter clinical trials,^2-4 bilayered living-cell therapy has been shown to improve healing rates in venous leg and diabetic foot ulcerations compared to standard of care. In a randomized, unmasked, multicenter study of 127 patients with venous leg ulcerations >1-month duration, Falanga and the Human Skin Equivalent Investigators Group² found that, after 6 months, the proportion of patients healed in the bilayered living-cell therapy was higher than that in the control group using compression therapy alone (63% versus 49%; P = 0.02). In a prospective, randomized, multicenter trial⁵ of diabetic foot ulcers treated with saline-moistened gauze control or bilayered living-cell therapy and conventional care (including extensive surgical debridement and foot offloading), the time to wound closure was 65 days in the treatment versus 90 days in the control group (P = 0.003).

     Several theories have been proposed to explain the improved healing rates in chronic wounds after the application of bilayered living-cell therapy. One popular theory is that it facilitates healing by delivering much-needed matrix materials and cytokine growth factors in the appropriate concentrations.^4,6 It also has been suggested that bilayered living-cell therapy may act similarly to an autologous split-thickness skin graft or a biologic dressing, both of which persist within the healed wound bed.