Foreskin fibroblast (neonatal)

Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates
Name
Foreskin fibroblast (neonatal)
Accession Number
DB10770
Type
Biotech
Groups
Approved
Biologic Classification
Cell transplant therapies
Other cell transplant therapies
Description

Foreskin fibroblast-like stromal cells (FDSCs) are progenitors isolated from human tissue that can differentiate into various cell types 2.

Also known as Dermagraft, this device is a cryopreserved human fibroblast-derived dermal substitute. Composed of fibroblasts, extracellular matrix, and a bioabsorbable scaffold, it effectively supports wound healing 3.

Dermagraft has only been available in the United States as an investigational device (IDE). Dermagraft for the treatment of diabetic foot ulcers was approved for sale in Canada in 1997. Dermagraft was introduced in the United Kingdom in October 1997, and several other European countries, as well as New Zealand and Australia. The device is available for commercial distribution in Australia, Canada, Finland, France, Hong Kong, Ireland, The Netherlands, New Zealand, Singapore, and The United Kingdom 3.

The impact of diabetic foot ulcers (DFU) on individuals and society is devastating. Failure to observe proper wound care in this condition often results in amputation. If wound closure is achieved, it is likely to delay the need for surgical intervention and provide other benefits such as improvements in productivity, mental outlook, social interactions, and time at work, in addition to decreased mortality 14.

Interestingly, it has been shown that human foreskin cells possess immunosuppressive properties, which are mediated by other processes than that reported for bone marrow/stromal stem cells 1. Dermagraft has been combined with Foreskin keratinocyte (neonatal) to create a drug beneficial to patients with open burn wounds 11.

Synonyms
  • foreskin fibroblast, neonatal
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
GintuitForeskin fibroblast (neonatal) + Bovine type I collagen + Foreskin keratinocyte (neonatal)Cellular SheetTopicalOrganogenesis2012-03-15Not applicableUs
Categories
UNII
T34C307W5N
CAS number
Not Available

Pharmacology

Indication

This device is indicated for use for the treatment of full-thickness, diabetic foot ulcers greater than six weeks duration which extends through the dermis, but without tendon, muscle, joint capsule or bone exposure. This drug should be used in conjunction with standard wound care regimens and in patients with an adequate blood supply to the involved foot 3.

Associated Conditions
Pharmacodynamics

This physiologically active dermal substitute is a scaffold upon which tissue can grow, allowing for effective healing of wounds 3.

Dermagraft is made from human fibroblast cells obtained from newborn foreskin tissue. During the manufacturing process, the human fibroblasts are placed onto a bioabsorbable polyglactin mesh scaffold. The fibroblasts grow to fill the interstices of this scaffold and secrete human dermal collagen, matrix proteins, and growth factors, as well as cytokines. This creates a three-dimensional human dermal substitute containing active, living cells. Dermagraft does not contain macrophages, lymphocytes, blood vessels, or hair follicles 3.

Among other cytokines, this device induces the production of interleukin 6 (IL-6). This gene encodes a cytokine that functions in inflammation and the maturation of B type immune cells. In addition the above, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is mainly produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The function this gene is involved in a wide variety of inflammation-associated disease states, including susceptibility to diabetes mellitus and systemic juvenile rheumatoid arthritis 8.

Mechanism of action

Dermagraft is a cryopreserved, human fibroblast-derived dermal substitute that contains fibroblasts, extracellular matrix, and a bioabsorbable polyglactin mesh scaffold 11. The fibroblasts are obtained from human newborn foreskin tissue. The fibroblasts are then placed on a scaffold and progress to proliferate and produce human dermal collagen, matrix proteins, growth factors, and cytokines. The above steps create a three-dimensional human dermal substitute with active human cells. Dermagraft does not contain macrophages, lymphocytes, blood vessels, nor hair follicles. It is available frozen as a single sheet (2 by 3 inches) for a single application 6.

TargetActionsOrganism
UInterleukin-6
agonist
Humans
AVascular endothelial growth factor receptor 1
agonist
Humans
UInterleukin-1 receptor type 1
agonist
Humans
UTGF-beta receptor type-2
agonist
Humans
UFibroblast growth factor 1
agonist
Humans
UInterferon gamma
agonist
Humans
UFibroblast growth factor receptor 2
agonist
Humans
UGranulocyte-macrophage colony-stimulating factor receptor subunit alpha
agonist
Humans
UPlatelet-derived growth factor receptor beta
agonist
Humans
UTransforming growth factor beta-1
agonist
Humans
UTumor necrosis factor
agonist
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

Learn more
Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more
Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

No serious adverse events were attributed to Dermagraft. Of the 314 patients enrolled in a preclinical study, 10.4% (17/163) of the patients developed an infection while 17.9% (27/151) of the control group patients developed an ulcer infection. Overall, 31/163 (19%) of the dermagraft group developed infection, cellulitis, or osteomyelitis. In the control group, 49/151 (32.5%) patients developed the same adverse events. Thus, there was a lower rate of infection, cellulitis, and osteomyelitis in the dermagraft treated group 3.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

References

General References
  1. Wada N, Bartold PM, Gronthos S: Human foreskin fibroblasts exert immunomodulatory properties by a different mechanism to bone marrow stromal/stem cells. Stem Cells Dev. 2011 Apr;20(4):647-59. doi: 10.1089/scd.2010.0246. Epub 2010 Oct 12. [PubMed:20712449]
  2. Huang HI, Chen SK, Wang RY, Shen CR, Cheng YC: Human foreskin fibroblast-like stromal cells can differentiate into functional hepatocytic cells. Cell Biol Int. 2013 Dec;37(12):1308-19. doi: 10.1002/cbin.10175. Epub 2013 Sep 16. [PubMed:23956153]
  3. FDA document,: SUMMARY OF SAFETY AND EFFECTIVENESS DATA [Link]
  4. Apligraf document, FDA [Link]
  5. Three-Dimensional Human Tissue Models That Incorporate Diabetic Foot Ulcer-Derived Fibroblasts Mimic In Vivo Features of Chronic Wounds [Link]
  6. Skin Substitutes for Treating Chronic Wounds [Internet] [Link]
  7. Human foreskin fibroblast produces interleukin-6 to support derivation and self-renewal of mouse embryonic stem cells [Link]
  8. IL6 interleukin 6 [ Homo sapiens (human) ] [Link]
  9. IFNλ Stimulates MxA Production in Human Dermal Fibroblasts via a MAPK-Dependent STAT1-Independent Mechanism [Link]
  10. Fibronectin human foreskin fibroblasts [Link]
  11. SUMMARY OF SAFETY AND EFFECTIVENESS DATA, Orcel [Link]
  12. Immortalized human skin fibroblast feeder cells support growth and maintenance of both human embryonic and induced pluripotent stem cells [Link]
  13. Pre-Clinical Demo Orcel [Link]
  14. SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) [Link]
  15. Advancement of wound care from grafts to bioengineered smart skin substitutes [Link]
  16. Premarket Approval (PMA) [Link]
External Links
Not Available
MSDS
Download (393 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2TerminatedTreatmentEdentulous Alveolar Ridge1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Cellular sheetTopical
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility1 mg/mL at 37 °CMSDS

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Interleukin-6 receptor binding
Specific Function
Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Inv...
Gene Name
IL6
Uniprot ID
P05231
Uniprot Name
Interleukin-6
Molecular Weight
23717.965 Da
References
  1. Human foreskin fibroblast produces interleukin-6 to support derivation and self-renewal of mouse embryonic stem cells [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
References
  1. Pre-Clinical Demo Orcel [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Transmembrane signaling receptor activity
Specific Function
Receptor for IL1A, IL1B and IL1RN. After binding to interleukin-1 associates with the corecptor IL1RAP to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependen...
Gene Name
IL1R1
Uniprot ID
P14778
Uniprot Name
Interleukin-1 receptor type 1
Molecular Weight
65401.91 Da
References
  1. Pre-Clinical Demo Orcel [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Type iii transforming growth factor beta receptor binding
Specific Function
Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Tran...
Gene Name
TGFBR2
Uniprot ID
P37173
Uniprot Name
TGF-beta receptor type-2
Molecular Weight
64567.1 Da
References
  1. Pre-Clinical Demo Orcel [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
S100 protein binding
Specific Function
Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.
Gene Name
FGF1
Uniprot ID
P05230
Uniprot Name
Fibroblast growth factor 1
Molecular Weight
17459.58 Da
References
  1. Pre-Clinical Demo Orcel [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Interferon-gamma receptor binding
Specific Function
Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrop...
Gene Name
IFNG
Uniprot ID
P01579
Uniprot Name
Interferon gamma
Molecular Weight
19348.165 Da
References
  1. Pre-Clinical Demo Orcel [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosi...
Gene Name
FGFR2
Uniprot ID
P21802
Uniprot Name
Fibroblast growth factor receptor 2
Molecular Weight
92024.29 Da
References
  1. Pre-Clinical Demo Orcel [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Receptor activity
Specific Function
Low affinity receptor for granulocyte-macrophage colony-stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells.
Gene Name
CSF2RA
Uniprot ID
P15509
Uniprot Name
Granulocyte-macrophage colony-stimulating factor receptor subunit alpha
Molecular Weight
46206.185 Da
References
  1. Pre-Clinical Demo Orcel [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
References
  1. Pre-Clinical Demo Orcel [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Type iii transforming growth factor beta receptor binding
Specific Function
Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negati...
Gene Name
TGFB1
Uniprot ID
P01137
Uniprot Name
Transforming growth factor beta-1
Molecular Weight
44340.685 Da
References
  1. Pre-Clinical Demo Orcel [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Tumor necrosis factor receptor binding
Specific Function
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da
References
  1. Pre-Clinical Demo Orcel [Link]

Drug created on December 01, 2015 13:04 / Updated on December 02, 2019 08:52