Dermal micro-organs, methods and apparatuses for producing and using the same

• US 8,293,463 B2
• Filed: 06/23/2011
• Issued: 10/23/2012
• Est. Priority Date: 11/05/2001
• Status: Expired due to Fees

• Current Assignee: Medgenics Medical Israel Ltd.
• Original Assignee: Medgenics Inc. (Avalo Therapeutics, Inc.)
• Inventors: Bellomo, Stephen F., Lippin, Itzhak, Piva, Guillermo Alberto, Rosenberg, Lior, Bukhman, Mordechay, Stern, Baruch S., Shalhevet, David, Shavitt, Menachem D., Pearlman, Andrew L., Shani, Noam, Almon, Einat
• Primary Examiner(s): Noble, Marcia S
• Application Number:
  US13/166,821
• Publication Number:
  US 20120003276A1
• Time in Patent Office: 488 Days
• Field of Search: 435/1.1, 435/325, 623/15.11
• US Class Current: 435/1.1
• 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 by marking A61B2090/395
• 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: A61P 17/00 Drugs for dermatological disorders
• 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 method of delivering erythropoietin to a subject comprising implanting into or underneath the skin a at least one genetically modified dermal micro-organ that expresses and secretes at least one recombinant gene product or at least a portion of said at least one recombinant gene product,

a. wherein said at least one recombinant gene product comprises erythropoietin;

b. wherein said genetically modified dermal micro-organ is autologous with said subject;

c. wherein said dermal micro-organ is an explant of living tissue consisting essentially of a plurality of dermal components and lacking a complete epidermal layer that substantially maintain the micro-architecture and three-dimensional structure of the dermal tissue from which they are obtained, and having dimensions selected so as to allow 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; and

d. wherein at least some of the cells of said genetically modified dermal micro-organ express and secrete at least a portion of said erythropoietin;

wherein said implanting of said at least one genetically modified dermal micro-organ delivers erythropoietin to said subject.

2. The method of claim 1, wherein said at least one genetically modified dermal micro-organ is a linear micro-organ.

3. The method of claim 2, wherein said linear micro-organ remains in a linear form after said implanting.

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

5. The method of claim 1, wherein said at least one genetically modified dermal organ includes fat tissue.

6. The method of claim 1, wherein said at least one genetically modified dermal organ comprises an in-vivo demarcation.

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

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

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

10. The method of claim 1, wherein said implanting under the skin is subcutaneous implanting.

11. The method of claim 1, wherein said at least one genetically modified dermal organ is 5-100 mm in length.

12. The method of claim 11, wherein said at least one genetically modified dermal organ is 10-60 mm in length.

13. The method of claim 12, wherein said at least one genetically modified dermal organ is 20-40 mm in length.

14. The method of claim 1, wherein said delivery of erythropoietin increases the percent hematocrit in said subject.

15. The method of claim 1, wherein said delivery of erythropoietin maintains the percent hematocrit in said subject.

16. The method of claim 15, wherein said percent hematocrit is maintained for at least one month.

17. The method of claim 1, wherein said delivery of erythropoietin increases and then maintains the percent hematocrit in said subject.

18. The method of claim 17, wherein said percent hematocrit is maintained for at least one month.

19. The method of claim 1, wherein said delivery of erythropoietin increases percent reticulocytes in said subject.

20. The method of claim 1, wherein said delivery of erythropoietin increases serum erythropoietin in said subject.