The Role of Fibroblasts in Tissue Engineering and Regeneration

T. Wong; J.A. McGrath; H. Navsaria

The British Journal of Dermatology. 2007;156(6):1149-1155.

Summary and Introduction

Fibroblasts are mesenchymal cells that can be readily cultured in the laboratory and play a significant role in epithelial-mesenchymal interactions, secreting various growth factors and cytokines that have a direct effect on epidermal proliferation, differentiation and formation of extracellular matrix. They have been incorporated into various tissue-engineered products such as Dermagraft^® (Advanced BioHealing, La Jolla, CA, U.S.A.) and Apligraf^® (Novartis, Basel, Switzerland) and used for a variety of clinical applications, including the treatment of burns, chronic venous ulcers and several other clinical applications in dermatology and plastic surgery. In this article we review the cell biology of dermal fibroblasts and discuss past and current experience of the clinical use of cultured fibroblasts.

Fibroblasts are a heterogeneous population of cells found in numerous tissues and are of mesenchymal origin. Fibroblasts from different anatomical sites all have similar morphology but DNA-microarray studies have demonstrated that fibroblasts in different anatomical sites have their own gene-expression profile and characteristic phenotypes, synthesizing extracellular matrix (ECM) proteins and cytokines in a site-specific manner.^[1] Dermal fibroblasts have numerous functions, not only in synthesizing and depositing ECM components, but also proliferation and migration in response to chemotactic, mitogenic and modulatory cytokines, and also autocrine and paracrine interactions.^[2]

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Summary and Introduction
Culturing Fibroblasts
Allogeneic vs. Autologous Fibroblasts
Epithelial-mesenchymal Interactions and Tissue Engineering
Clinical Applications
Conclusion
References

A Summary of Dermal and Epidermal-dermal Replacement Matrices That Currently Have US Food and Drug Administration (FDA) Approval
Product	Epidermal component	Dermal component	Preservation	FDA-approved uses	Cost^a
Whole skin
Allogeneic cadaver skin (Euro Skin Bank)	Epidermis	Cellular dermis	Glycerolized	Burns, scar revision	€0·85 for 1 cm²
Alloderm^® (LifeCell Corporation, Woodlands, TX, U.S.A.)	None	Acellular dermis	Freeze-dried	Burns, scar revision	£1015 for 5 × 10 cm
De-epidermized dermis (DED) (National skin banks)	None	Acellular dermis	Cryopreserved, lyophilized, glycerolized	Burns, scar revision
HYAFF^® technologies
Hyalograft-3D^® (Fidia Advanced Biopolymers srl, Abano Terme, Italy)	Silicone membrane	Esterified hyaluronic acid matrix with autologous fibroblasts	Stored in cool, dry place	Burns, diabetic foot ulcers
Hyalomatrix^® (Fidia Advanced Biopolymers srl)	Silicone membrane	Hyaluronic acid matrices with variable esterification	Stored in cool, dry place	Burns, diabetic foot ulcers
Laserskin^® (Fidia Advanced Biopolymers srl)	100% esterified hyaluronic acid membrane with laser-drilled micropores and keratinocytes	None	Stored in cool, dry place	Biodegradable keratinocyte delivery system
Dermal substitutes
Dermagraft^® (Advanced BioHealing, La Jolla, CA, U.S.A.)	None	Bioabsorbable polyglactin mesh with viable neonatal foreskin fibroblasts	Cryopreserved	Burns, diabetic foot ulcers	£300
TransCyte^® (Dermagraft TC, Advanced BioHealing)	Silicone membrane	Nylon mesh coated with porcine collagen with nonviable neonatal foreskin fibroblasts	Cryopreserved	Burns, diabetic foot ulcers	£1000
Integra^TM (Integra LifeSciences Corporation, Plainsboro, NJ, U.S.A.)	Silicone membrane	Bovine collagen I and shark chondroitin-6-sulphate	Isopropyl alcohol at 2-8 °C	Burns, scar revision	£1346 for 8 × 10 cm
Composite skin equivalents
Apligraf^® (Novartis Pharmaceuticals, Basel, Switzerland; Organogenesis, Canton, MA, U.S.A.)	Living neonatal foreskin keratinocytes	Bovine collagen I with viable neonatal foreskin fibroblasts	Stored at 37 °C	Burns, venous ulcers, diabetic ulcers	$1200 for 44 cm²
OrCel^TM (Ortec International Inc., New York, NY, U.S.A.)	Living allogeneic keratinocytes cultured on bilayered collagen matrix	Bilayered matrix of bovine collagen I with viable fibroblasts	Stored at 37 °C	Burns
Epidermal substitutes
Epicel^® (Genzyme Corporation, Cambridge, MA, U.S.A.)	Viable cultured autologous keratinocytes	None	Stored at 37 °C	Burns, chronic venous ulcers, diabetic leg ulcers, skin graft donor sites, scar revision	$1164 for 50 cm²
Isolagen^® (Isolagen Technologies Inc., Paramus, NJ, U.S.A.)	None	Autologous fibroblasts	Room temperature	Cosmetic application, wrinkles	£3500

^aE-mails were sent to all the companies listed in the Table but not all responded. The prices vary in different countries. Costs represent August 2006 prices.

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