CA2483547A1 - Keratinocytes expressing exogenous angiogenic growth factors - Google Patents

Keratinocytes expressing exogenous angiogenic growth factors Download PDF

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Publication number
CA2483547A1
CA2483547A1 CA002483547A CA2483547A CA2483547A1 CA 2483547 A1 CA2483547 A1 CA 2483547A1 CA 002483547 A CA002483547 A CA 002483547A CA 2483547 A CA2483547 A CA 2483547A CA 2483547 A1 CA2483547 A1 CA 2483547A1
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CA
Canada
Prior art keywords
composition
keratinocytes
gene
exogenous
graft
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Granted
Application number
CA002483547A
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French (fr)
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CA2483547C (en
Inventor
Allen Comer
Michael Hoffmann
Lynn-Allen Hoffmann
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Stratatech Corp
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Individual
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Priority to CA2763666A priority Critical patent/CA2763666C/en
Publication of CA2483547A1 publication Critical patent/CA2483547A1/en
Application granted granted Critical
Publication of CA2483547C publication Critical patent/CA2483547C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/515—Angiogenesic factors; Angiogenin
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0697—Artificial constructs associating cells of different lineages, e.g. tissue equivalents
    • C12N5/0698—Skin equivalents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/165—Vascular endothelial growth factor [VEGF]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/17—Angiopoietin
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/09—Coculture with; Conditioned medium produced by epidermal cells, skin cells, oral mucosa cells
    • C12N2502/094—Coculture with; Conditioned medium produced by epidermal cells, skin cells, oral mucosa cells keratinocytes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
    • C12N2502/1323—Adult fibroblasts
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/99—Coculture with; Conditioned medium produced by genetically modified cells

Abstract

The present invention relates to in vitro cultured skin tissue, and in particular to cultured skin tissue comprising exogenous genes encoding angiogenic growth factors. In some embodiments, the keratinocytes express exogenous angiopoietin-1 or a member of the VEGF family, preferably VEGF-A. In particularly preferred embodiments, the keratinocytes are incorporated into cultured skin tissue.

Claims (23)

1. A composition comprising keratinocytes, said keratinocytes comprising at least one exogenous angiogenic factor operably linked to a promoter.
2. The composition of Claim 1, wherein said keratinocytes are selected from the group consisting of primary keratinocytes and immortalized keratinocytes.
3. The composition of Claim 2, wherein said immortalized keratinocytes are NIKS cells.
4. The composition of Claims 1-3, further comprising a dermal equivalent.
5. The composition of Claim 4, wherein said dermal equivalent comprises collagen and fibroblasts.
6. The composition of Claims 1-5, wherein said keratinocytes are stratified, thereby forming cultured skin tissue.
7. The composition of Claim 6, wherein said cultured skin tissue is stratified into squamous epithelia.
8. The composition of Claims 1-7, wherein said angiogenic factor is selected from the group consisting of a VEGF gene and an angiopoietin gene.
9. The composition of Claim 8, wherein said VEGF gene is VEGF-A.
10. The composition of Claim 8, wherein said angiopoietin gene is angiopoietin-1.
11. The composition of Claims 1-10, wherein said promoter is inducible.
12. The composition of Claim 11, wherein said inducible promoter is a Tet-responsive promoter.
13. The composition of Claims 1-12, wherein said composition is a human skin equivalent.
14. The composition of Claims 1-13, further comprising at least two sub-populations of keratinocytes, one of said subpopulations comprising an exogenous VEGF gene and the other of said populations comprising an exogenous angiopoietin gene.
15. The composition of Claim 8, wherein said VEGF-A gene is encoded by SEQ
ID NO:1 or sequences that hybridize to SEQ ID NO:1 under conditions of low stringency.
16. The composition of Claim 8, wherein said angiopoietin-1 gene is encoded by SEQ ID NO:2 or sequences that hybridize to SEQ ID NO:2 under conditions of low stringency.
17. A skin graft comprising keratinocytes, wherein said keratinocytes comprise an exogenous HIF-1 gene operably linked to an inducible promoter
18. A skin graft composition comprising at least first and second sub-populations of keratinocytes, wherein said first subpopulation of keratinocytes is transfected with a first exogenous angiogenic factor operably linked to an inducible promoter and said second sub-population is transfected with a second exogenous angiogenic factor operably linked to an inducible promoter.
19. A composition of Claims 1-18 for use in treating burns.
20. A composition of Claims 1-18 for use in treating wounds.
21. A method of treatment comprising:
a) providing a patient in need of a graft and the composition of Claim 1; and b) contacting said patient with said composition of Claim 1 under conditions such that said graft vascularizes.
22. A method of treatment comprising:
a) providing a patient in need of graft and a human skin equivalent, wherein said human skin equivalent comprises keratinocytes comprising at least one exogenous angiogenic factor operably linked to a promoter inducible by application of a topical substance; and b) contacting said patient with said human skin equivalent; and c) applying said topical substance to said graft under conditions such that said human skin equivalent vascularizes.
23. A composition according to Claim 1 substantially described herein in any of the examples.
CA2483547A 2002-04-30 2003-04-29 Keratinocytes expressing exogenous angiogenic growth factors Expired - Lifetime CA2483547C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2763666A CA2763666C (en) 2002-04-30 2003-04-29 Keratinocytes expressing exogenous angiogenic growth factors

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US37648802P 2002-04-30 2002-04-30
US60/376,488 2002-04-30
US10/425,784 2003-04-29
PCT/US2003/013327 WO2003093418A2 (en) 2002-04-30 2003-04-29 Keratinocytes expressing exogenous angiogenic growth factors
US10/425,784 US7498167B2 (en) 2002-04-30 2003-04-29 Keratinocytes expressing exogenous angiogenic growth factors

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CA2763666A Division CA2763666C (en) 2002-04-30 2003-04-29 Keratinocytes expressing exogenous angiogenic growth factors

Publications (2)

Publication Number Publication Date
CA2483547A1 true CA2483547A1 (en) 2003-11-13
CA2483547C CA2483547C (en) 2012-03-20

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CA2483547A Expired - Lifetime CA2483547C (en) 2002-04-30 2003-04-29 Keratinocytes expressing exogenous angiogenic growth factors

Country Status (9)

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US (5) US7498167B2 (en)
EP (1) EP1549738B1 (en)
JP (1) JP4753577B2 (en)
AT (1) ATE465242T1 (en)
CA (1) CA2483547C (en)
DE (1) DE60332256D1 (en)
IL (3) IL164817A0 (en)
NZ (1) NZ536205A (en)
WO (1) WO2003093418A2 (en)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL164817A0 (en) 2002-04-30 2005-12-18 Stratatech Corp Keratinocytes expressing exogenous angiogenic growth factors
CA2600177C (en) 2005-03-01 2011-06-14 Stratatech Corporation Human skin equivalents expressing exogenous polypeptides
EP2215212B1 (en) 2007-11-14 2017-08-30 Stratatech Corporation Cold storage of organotypically cultured skin equivalents for clinical applications
DK2352472T3 (en) 2008-11-04 2017-04-10 Stratatech Corp Dried and irradiated skin equivalents ready to use
US20100330046A1 (en) * 2009-05-21 2010-12-30 Stratatech Corporation Human skin substitutes expressing il-12
TWI488966B (en) * 2010-07-09 2015-06-21 優普生物科技股份有限公司 Dna vaccine
US8978234B2 (en) 2011-12-07 2015-03-17 MoMelan Technologies, Inc. Methods of manufacturing devices for generating skin grafts
US9597111B2 (en) 2010-08-06 2017-03-21 Kci Licensing, Inc. Methods for applying a skin graft
JP2012205516A (en) * 2011-03-29 2012-10-25 Osaka Univ Method for producing artificial skin model, and artificial skin model
US20140065110A1 (en) * 2012-08-31 2014-03-06 The Regents Of The University Of California Genetically modified msc and therapeutic methods
US9663564B2 (en) 2013-03-15 2017-05-30 The Regents Of The University Of California Vectors and methods to treat ischemia
WO2014072941A1 (en) 2012-11-09 2014-05-15 Marco Archetti Diffusible factors and cancer cells
ES2705043T3 (en) 2013-03-13 2019-03-21 Stratatech Corp Cryopreservation of viable human skin substitutes
CN105636532B (en) 2013-03-14 2019-06-21 凯希特许有限公司 For acquiring the absorbability substrate of skin graft
EP3089682B1 (en) 2013-12-31 2017-04-19 KCI Licensing, Inc. Sensor systems for skin graft harvesting
US10463392B2 (en) 2013-12-31 2019-11-05 Kci Licensing, Inc. Fluid-assisted skin graft harvesting
WO2016164890A1 (en) 2015-04-09 2016-10-13 Kci Licensing, Inc. Soft-tack, porous substrates for harvesting skin grafts
WO2017079439A1 (en) 2015-11-03 2017-05-11 Kci Licensing, Inc. Device for creating an epidermal graft sheet
WO2017143229A1 (en) * 2016-02-19 2017-08-24 Kci Licensing, Inc. Transfected epidermal grafts and methods of making the same
EP3551746A1 (en) * 2016-12-09 2019-10-16 The University of Chicago Tissue organoids
EP4034038A4 (en) * 2019-09-27 2023-11-01 Stratatech Corporation Methods for treating acute wounds and improving outcomes
WO2021231775A1 (en) * 2020-05-13 2021-11-18 Stratatech Copporation Viable bioengineered skin constructs
AU2022287965A1 (en) * 2021-06-08 2023-12-14 Stratatech Corporation Viable bioengineered allogeneic cellularized skin constructs that secrete soluble factors associated with regenerative wound healing
WO2023017494A1 (en) * 2021-08-13 2023-02-16 Triovance Holding Llc A skin substitute composition and methods of producing and using the same

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US448096A (en) * 1891-03-10 Hydrant
US4485096A (en) 1982-02-26 1984-11-27 Massachusetts Institute Of Technology Tissue-equivalent and method for preparation thereof
IL95429A (en) 1989-09-15 1997-09-30 Organogenesis Living tissue equivalents comprising hydrated collagen lattice and a collagen gel and their production
US5292655A (en) * 1990-01-29 1994-03-08 Wille Jr John J Method for the formation of a histologically-complete skin substitute
HUT63319A (en) 1990-04-24 1993-08-30 Mark Eisenberg Method for producing composition equivalent with living skin
US5292566A (en) * 1990-05-22 1994-03-08 National Label Company Battery label with non-shrinkable top layer
IT1248934B (en) 1990-06-01 1995-02-11 Fidia Spa BIOCOMPATIBLE PERFORATED MEMBRANES, PROCESSES FOR THEIR PREPARATION, THEIR USE AS A SUPPORT FOR THE IN VITRO GROWTH OF EPITHELIAL CELLS, ARTIFICIAL LEATHER THUS OBTAINED AND THEIR USE IN LEATHER TRANSPLANTS
US5693332C1 (en) 1995-08-11 2001-01-09 Univ California Human keratinocytes supported on a hydrophilic membrane and methods of using same to effect wound closure
US5968546A (en) 1997-05-16 1999-10-19 Baur; Marcus Keratinocyte culture from precursor cells
US20010048917A1 (en) * 1998-03-09 2001-12-06 Warren Hoeffler Skin equivalent and methods of forming and using same
US5989837A (en) 1998-07-13 1999-11-23 Wisconsin Alumni Research Foundation Immortalized human keratinocyte cell line
US20030152562A1 (en) * 2001-10-23 2003-08-14 Yissum Research Development Company Of The Hebrew University Of Jerusalem Vitro micro-organs, and uses related thereto
US6458382B1 (en) * 1999-11-12 2002-10-01 Mirus Corporation Nucleic acid transfer complexes
AU2002224471A1 (en) * 2000-11-01 2002-05-15 Aventis Pharma S.A. In vivo stimulation of angiogenic activity
EP1404809B1 (en) * 2001-03-02 2013-12-11 Stratatech Corporation Improved skin substitutes and uses thereof
US6849718B2 (en) 2001-03-20 2005-02-01 Dana Farber Cancer Institute, Inc. Muteins of hypoxia inducible factor alpha and methods of use thereof
WO2003018621A2 (en) * 2001-08-23 2003-03-06 Oxford Biomedica (Uk) Limited Genes
US6838430B2 (en) 2001-09-28 2005-01-04 The Regents Of The University Of California Use of HIF-1a variants to accelerate wound healing
US20040190793A1 (en) 2002-03-01 2004-09-30 Rorvig Mark E. Method for retrieving images by content measure metadata encoding
IL164817A0 (en) 2002-04-30 2005-12-18 Stratatech Corp Keratinocytes expressing exogenous angiogenic growth factors
US7462448B2 (en) 2002-08-02 2008-12-09 Stratatech Corporation Species specific DNA detection
CA2527822A1 (en) 2003-05-30 2004-12-23 Stratatech Corporation Room temperature storage of organs
EP3100611B1 (en) 2003-08-01 2018-09-12 Stratatech Corporation Human skin equivalents expressing exogenous polypeptides

Also Published As

Publication number Publication date
EP1549738B1 (en) 2010-04-21
CA2483547C (en) 2012-03-20
EP1549738A2 (en) 2005-07-06
US7915042B2 (en) 2011-03-29
WO2003093418A2 (en) 2003-11-13
IL195518A (en) 2012-08-30
AU2003228755A1 (en) 2003-11-17
IL164817A (en) 2010-12-30
US20040009591A1 (en) 2004-01-15
US7807148B2 (en) 2010-10-05
JP4753577B2 (en) 2011-08-24
IL164817A0 (en) 2005-12-18
US20110286985A1 (en) 2011-11-24
US20110059057A1 (en) 2011-03-10
US7498167B2 (en) 2009-03-03
ATE465242T1 (en) 2010-05-15
EP1549738A4 (en) 2006-11-02
DE60332256D1 (en) 2010-06-02
WO2003093418A3 (en) 2005-04-21
JP2006509529A (en) 2006-03-23
US20090169528A1 (en) 2009-07-02
US20050013807A1 (en) 2005-01-20
US7988959B2 (en) 2011-08-02
NZ536205A (en) 2008-04-30
US8808685B2 (en) 2014-08-19

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