| Candidate ID: | R1324 |
| Source ID: | DB10772 |
| Source Type: | approved |
| Compound Type: |
biotech
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| Compound Name: |
Foreskin keratinocyte (neonatal)
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| Synonyms: |
foreskin keratinocyte, neonatal
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| Molecular Formula: |
--
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| SMILES: |
--
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| DrugBank Description: |
Skin, the largest organ of the human body, plays the main role in protecting the body from mechanical damage. It is composed of epidermal, dermal and hypodermal layers. The barrier function of the skin owed to its avascular epidermal layer, which is made mainly of keratinocytes. The keratinocytes form a stratified epithelium, with growing basal cells at the innermost layer and the keratinized, and mostly impermeable outer stratum corneum layer on the surface .
Foreskin keratinocytes are a form of skin cells that are cultured as a skin cell replacement for wounds, to accelerate wound closure and healing , .
The defining moment in skin culture was in 1975 when Rheinwald and Green successfully grew human keratinocytes on lethally irradiated murine fibroblasts. In 1981, O’Conner and his group utilized cultured autologous epithelium to coat burn defects for the first time. To construct a "living" alternative, a dermal substitute based on collagen I gel was created with mesenchymal cells such as fibroblasts. When an epidermal layer was added, this approach became known as "skin equivalent", "composite culture" or "organotypical culture" .
Foreskin keratinocytes are an important ingredient in several skin substitutes , used for various indications.
Keratinocytes are derived from neonatal foreskins and used to create a drug called _Apligraf_, a mixture of and keratinocytes. A gel made of bovine collagen is used as the matrix for cell growth and differentiation. Apligraf has been useful in the treatment of venous leg ulcers and diabetic foot ulcers, by increasing rates of wound healing and decreasing the time required for closure of wounds .
Orcel, another skin substitute, is similar to Apligraf since it contains both fibroblasts and keratinocytes derived from neonatal foreskin, but in addition, utilizes a type I collagen sponge as its matrix. It is used for grafting onto partial-thickness wounds, where it offers a favorable matrix for host cell migration .
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| CAS Number: |
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| Molecular Weight: |
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| DrugBank Indication: |
For chronic leg ulcers and diabetic foot .
Orcel is indicated for use with standard therapeutic compression for the treatment of non-infected partial and full-thickness skin ulcers due to venous insufficiency of greater than 1 month in duration and which have not effectively responded to conventional ulcer therapy. Orcel is also for use with standard diabetic foot ulcer care for the treatment of full-thickness neuropathic diabetic foot ulcers of greater than 3 weeks in duration which have not effectively responded to conventional ulcer therapy, and which extend through the dermis but without tendon, muscle, capsule or bone involvement .
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| DrugBank Pharmacology: |
Foreskin keratinocyte grafts lead to the re‐epithelialization of partial deep severe burns, thus allowing complete wound closure, and improves the condition of scars .
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| DrugBank MoA: |
Foreskin keratinocytes promote the proliferation of epithelial (skin) cells.
Epidermal keratinocytes (skin cells) are very specialized epithelial cells designed for a very specific function, which is the separation of the organism from its outside environment. To provide this protection, the cells synthesize precursors and assemble them into two distinct structures, the cornified envelope and keratin intermediate filaments. The intermediate filaments are formed by keratin monomers and the cornified envelope is assembled from a protein called _involucrin_ and several other proteins .
The following is a description of the mechanism of action of foreskin keratinocytes in various devices, while combined with other types of cells:
Orcel (epidermal keratinocytes and dermal fibroblasts) are cultured in two separate layers into a Type I bovine collagen sponge. Donor dermal fibroblasts are cultured on and within the porous sponge side of the collagen matrix while keratinocytes, from the same donor, are also cultured on the covered, non-porous side of the collagen matrix. Orcel acts as an absorbable matrix, providing a fertile environment for host cell migration and has been shown to contain the following cell-expressed cytokines with growth factors: FGF-1 (bFGF), NGF, GM-CSF, IL-1α, IL-1β, IL-6, HGF, KGF-1 (FGF- 7), M-CSF, PDGF-AB, TGF-α, TGF-β1, TGF-β2, and VEGF. DNA analysis performed on two Orcel treated donor site patient tissue samples demonstrated no trace of allogeneic cell DNA after 2-3 weeks post-treatment. Orcel is manufactured under aseptic conditions from human neonatal foreskin tissue .
Apligraf is supplied as a living, bi-layered skin substitute: the epidermal layer is formed by human keratinocytes and has a well-differentiated stratum corneum; the dermal layer is composed of human fibroblasts in a bovine Type I collagen lattice. While matrix proteins and cytokines found in human skin are present in Apligraf, Apligraf does not contain Langerhans cells, melanocytes, macrophages, lymphocytes, blood vessels or hair follicles. In a 10 patient venous leg ulcer study to determine the longevity of Apligraf cells, 2 of 8 patients evaluated at 4 weeks demonstrated Apligraf DNA. Neither of these patients showed Apligraf DNA at 8 weeks .
For dental applications, Gintuit (Allogeneic Cultured Keratinocytes and Fibroblasts in Bovine Collagen) is an allogeneic cellularized scaffold product indicated for topical application to a surgically created vascular wound bed in the treatment of mucogingival conditions in adults .
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| Targets: |
Fibroblast growth factor 1 agonist; Epidermal growth factor receptor agonist; Granulocyte-macrophage colony-stimulating factor receptor subunit alpha agonist; Interleukin-1 beta agonist; Interleukin-6 agonist; Interferon gamma agonist; Fibroblast growth factor receptor 2 agonist; Platelet-derived growth factor receptor alpha agonist; TGF-beta receptor type-2 agonist; Transforming growth factor beta-1 agonist; Tumor necrosis factor agonist; Vascular endothelial growth factor A agonist
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| Inclusion Criteria: |
Target associated
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