The Longevity of a Bilayered Skin Substitute After Application to Venous Ulcers

Abstract

Background: A bilayered skin substitute composed of allogeneic keratinocytes and fibroblasts in a collagen gel has been approved by the US Food and Drug Administration for the treatment of venous and diabetic ulcers. Its mechanism of action has not been fully determined. Objective: To determine the longevity of allogeneic fibroblasts and keratinocytes in a bilayered skin substitute in patients with venous leg ulcers. Methods: Ten patients with venous leg ulcers were treated with a bilayered skin substitute on day 0, days 3 to 5, and weeks 1 through 3. Biopsy specimens of the grafted wound were taken. We used polymerase chain reaction analysis to determine whether allogeneic DNA was present in the biopsy specimens. Results: We detected allogeneic DNA in 2 of 8 specimens at 1 month after initial grafting. Neither of the 2 patients showed persistence of allogeneic DNA at 2 months after initial grafting. Conclusions: Allogeneic cells from a bilayered skin substitute do not appear to survive permanently after grafting for treatment of venous leg ulcers. Other mechanisms of action might include cytokine release, structural support, or provision of a moist wound environment.

Regenerative Medicine: Charting a New Course in Wound Healing

“…The latter do not engraft, but rather survive for a limited time, presumably releasing growth factors, synthesizing matrix, and recruiting endogenous stem cells. 30,31 Mesenchymal stem cells, found primarily not only in the bone marrow but also in adipose, vascular, muscle, and dermal tissue, are a highly active topic of research because of their ability to differentiate into multiple connective tissues, such as bone, cartilage, muscle, bone marrow stroma, tendon/ligament, fat, and dermis. 32 Furthermore, these cells secrete numerous immunoregulatory and regenerative molecules.…”

Human cell therapy for venous leg ulcers

“…As measured by in situ hybridization for donor cell Y-chromosome, the allogeneic cells persisted in female recipients for only approximately four weeks [85][86][87]. Reports concerning cell persistence [85,87] were contrary to the published academic experience, but eventually it was understood that histologic constructions are not necessary because the cells begin to die very soon after application [88]. Any barrier or water loss function provided by the engineered tissues is very short lived.…”

A Bioengineered Human Skin Tissue for the Treatment of Infected Wounds

“…22,23 However, clinical findings with BSS therapies suggest that cultured skin tissue is unlikely to be acutely rejected in humans. [24][25][26][27][28] Skin substitutes are gradually replaced by the patient's skin with no excessive inflammation or other signs of acute rejection. [25][26][27][28] Finally, a limitation of all cell-based BSS therapies is the high cost of manufacturing.…”

“…[24][25][26][27][28] Skin substitutes are gradually replaced by the patient's skin with no excessive inflammation or other signs of acute rejection. [25][26][27][28] Finally, a limitation of all cell-based BSS therapies is the high cost of manufacturing. However, this may be counterbalanced by an improved wound healing timeline, which would result in shorter patient hospitalization.…”