Chronic wound healing by fetal cell therapy may be explained by differential gene profiling observed in fetal versus old skin cells

Abstract

a b s t r a c tEngineering of fetal tissue has a high potential for the treatment of acute and chronic wounds of the skin in humans as these cells have high expansion capacity under simple culture conditions and one organ donation can produce Master Cell Banks which can fabricate over 900 million biological bandages (9 Â 12 cm). In a Phase 1 clinical safety study, cases are presented for the treatment of therapy resistant leg ulcers. All eight patients, representing 13 ulcers, tolerated multiple treatments with fetal biological bandages showing no negative secondary effects and repair processes similar to that seen in 3rd degree burns. Differential gene profiling using Affymetrix gene chips (analyzing 12,500 genes) were accomplished on these banked fetal dermal skin cells compared to banked dermal skin cells of an aged donor in order to point to potential indicators of wound healing. Families of genes involved in cell adhesion and extracellular matrix, cell cycle, cellular signaling, development and immune response show significant differences in regulation between banked fetal and those from banked old skin cells: with approximately 47.0% of genes over-expressed in fetal fibroblasts. It is perhaps these differences which contribute to efficient tissue repair seen in the clinic with fetal cell therapy.

The Wound Healing Process: An Overview of the Cellular and Molecular Mechanisms

“…Novel techniques of topical growth factor application and incisional priming with PDGF or IL-1 can optimize both the cellular and molecular environment, thus decreasing healing time by modifying inflammation and accelerating the proliferative phase. 91,92 Electrical field stimulation may optimize the remodelling phase by promoting more efficient fibroblast recruitment and collagen deposition, 93 -96 prosthetic materials can favour tissue repair, 4,97 and gene therapy, 98 which is currently in pre-clinical development, may be able to provide a way for selective healing.…”

Strategies for Improving the Repair of Focal Cartilage Defects

“…Thus, Darwiche et al propose epiphyseal chondroprogenitors as a stable cell source for cartilage cell therapy [105]. Indeed, extraordinary ability for self-repair has been shown by fetal cartilage cells [106], as well as an immune-modulatory activity [107,108].…”

Human cell therapy for venous leg ulcers

“…Fetal-derived fibroblasts have recently been tested in VLU, with 62% healing after up to 31 weeks of treatment [64]. However, the use of fetal tissue does not appear to offer any advantages.…”