DERMAL MICRO-ORGANS, METHODS AND APPARATUSES FOR PRODUCING AND USING THE SAME

• US 20100150878A1
• Filed: 10/01/2009
• Published: 06/17/2010
• Est. Priority Date: 11/05/2001
• Status: Active Grant

• Current Assignee: Medgenics Medical Israel Ltd.
• Original Assignee: Medgenics Inc. (Avalo Therapeutics, Inc.)
• Inventors: Pearlman, Andrew L., Shani, Noam, Shavitt, Menachem D., BELLOMO, Stephen F., Shalhevet, David, Stern, Baruch S., Almon, Einat, Rosenberg, Lior, Bukhman, Mordechay, Lippin, Itzhak, Piva, Guillermo Alberto
• Granted Patent: US 8,088,568 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61B 10/0275 with sample notch, e.g. on the side of inner stylet
• CPC Class Codes: A61B 17/32053 Punch like cutting instruments, e.g. using a cylindrical or oval knife A61B17/326 takes precedence; trepans A61B17/1695; for use on the cornea A61F9/007
• CPC Class Codes: A61B 17/322 Skin grafting apparatus
• CPC Class Codes: A61B 2017/0023 disposable
• CPC Class Codes: A61B 2017/00969 used for transplantation
• CPC Class Codes: A61B 2017/2808 Clamp, e.g. towel clamp
• CPC Class Codes: A61B 2017/320052 Guides for cutting instruments
• CPC Class Codes: A61B 2017/320064 with tissue or sample retaining means
• CPC Class Codes: A61B 2017/3225 with processing of harvested tissue
• CPC Class Codes: A61B 2217/005 with suction drainage system
• CPC Class Codes: A61F 2/105 Skin implants, e.g. artificial skin
• CPC Class Codes: A61K 35/36 Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells islets of Langerhans A61K35/39
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/2066 IL-10
• CPC Class Codes: A61K 38/215 IFN-beta
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: C12N 2502/094 keratinocytes
• CPC Class Codes: C12N 2502/1323 Adult fibroblasts
• CPC Class Codes: C12N 2510/00 : Genetically modified cells
• CPC Class Codes: C12N 5/0698 : Skin equivalents
• CPC Class Codes: Y10T 83/929 : Tool or tool with support

Abstract

Embodiments of the present invention provide Dermal Micro-organs (DMOs), methods and apparatuses for producing the same. Some embodiments of the invention provide a DMO including a plurality of dermal components, which substantially retain the micro-architecture and three dimensional structure of the dermal tissue from which they are derived, having dimensions selected so as to allow passive diffusion of adequate nutrients and gases to cells of the DMO and diffusion of cellular waste out of the cells so as to minimize cellular toxicity and concomitant death due to insufficient nutrition and accumulation of waste in the DMO. Some embodiments of the invention provide methods and apparatuses for harvesting the DMO. An apparatus for harvesting the DMO may include, according to some exemplary embodiments, a support configuration to support a skin-related tissue structure from which the DMO is to be harvested, and a cutting tool able to separate the DMO from the skin-related tissue structure. Other embodiments are described and claimed.

Claims

1. A genetically modified dermal micro-organ expressing at least one recombinant gene product, said dermal micro-organ comprising a plurality of dermal components, which retain the micro-architecture and three-dimensional structure of the dermal tissue from which they are derived, having dimensions selected so as to enable passive diffusion of adequate nutrients and gases to cells of said dermal micro-organ and diffusion of cellular waste out of said cells so as to minimize cellular toxicity and concomitant death due to insufficient nutrition and accumulation of waste in said dermal micro-organ, wherein at least some of said cells express at least a portion of at least one recombinant gene product, and wherein said recombinant gene product is Factor VIII.

2. The genetically modified dermal micro-organ of claim 1, wherein said dermal micro-organ includes at least part of the cross-section of the dermis.

3. The genetically modified dermal micro-organ of claim 1, wherein said dermal micro-organ further comprises fat tissue.

4. The genetically modified dermal micro-organ of claim 1, wherein said at least one recombinant gene product is naturally produced by an organ from which the dermal micro-organ is derived.

5. The genetically modified dermal micro-organ of claim 1, wherein said at least one recombinant gene product is not naturally produced by the organ from which the dermal micro-organ is derived.

6. The genetically modified dermal micro-organ of claim 1, wherein said genetically modified dermal micro-organ comprises an in-vivo demarcation.

7. The genetically modified dermal micro-organ of claim 6, wherein said in-vivo demarcation comprises an ink or stain on the peripheral surface of said micro-organ.

8. The genetically modified dermal micro-organ of claim 6, wherein said in-vivo demarcation comprises a green fluorescent protein (GFP) gene or Luciferase reporter gene expressed by said micro-organ.

9. The dermal micro organ of claim 1, wherein said dermal micro-organ does not produce keratin.

10. The genetically modified dermal micro-organ of claim 1, wherein said dermal micro-organ is 10-60 mm in length.

11. The genetically modified dermal micro-organ of claim 10, wherein said dermal micro-organ is 20-40 mm in length.

12. The genetically modified dermal micro-organ of claim 1, wherein at least one dimension of the cross section of said genetically modified dermal micro-organ is 0.5-3.5 mm.

13. The genetically modified dermal micro-organ of claim 1, wherein said dermal micro-organ is harvested using a harvester with an inner diameter of 1-2 mm.

14. The genetically modified dermal micro-organ of claim 1, wherein said dermal micro-organ comprises fibroblasts, epithelial components, nerve endings, sweat glands, sebaceous glands, blood and lymph vessels, elastin fibers, collagen fibers, endothelial components, immune system derived cells, extra-cellular matrix, or a combination thereof.

15. The genetically modified dermal micro-organ of claim 1, wherein said dermal micro-organ secretes said at least one recombinant gene product.

16. The genetically modified dermal micro-organ of claim 1, wherein said dermal micro-organ is viable in-vitro for at least several days.

17. The genetically modified dermal micro-organ of claim 1, wherein said dermal micro-organ is viable in-vitro for at least several weeks.

18. The genetically modified dermal micro-organ of claim 1, wherein said dermal micro-organ is implanted subcutaneously.

19. The genetically modified dermal micro-organ of claim 1, wherein said dermal micro-organ is implanted into the skin.

20. A method of inducing a local or systemic physiological effect in a subject comprising implanting in the body a genetically modified dermal micro-organ according to claim 1.

21. The method of claim 20, wherein implanting said genetically modified dermal micro-organ comprises implanting said dermal micro-organ into or underneath the skin.

22. A method of delivering a gene product of interest to a subject comprising implanting in the body the genetically modified dermal micro-organ of claim 1.

23. The method of claim 22, wherein implanting said genetically modified dermal micro-organ comprises implanting said genetically modified dermal micro-organ into or underneath the skin.

24. The method of claim 22, wherein said dermal micro-organ is derived from said subject.