Human xenografts for microbicide testing and anatomical modeling

• US 6,309,848 B1
• Filed: 07/24/2000
• Issued: 10/30/2001
• Est. Priority Date: 10/22/1999
• Status: Expired due to Fees

• Current Assignee: Penn State Research Foundation (Pennsylvania State University)
• Original Assignee: Penn State Research Foundation (Pennsylvania State University)
• Inventors: Howett, Mary K., Kreider, John W.
• Primary Examiner(s): Martin, Jill D.
• Application Number:
  US09/624,318
• Time in Patent Office: 463 Days
• Field of Search: 435/7.21, 800/3, 424/9.2, 424/9.1
• US Class Current: 424/9.2
• CPC Class Codes: A01K 67/0271 Chimeric vertebrates, e.g. comprising exogenous cells
• CPC Class Codes: G01N 33/5082 Supracellular entities, e.g. tissue, organisms

Abstract

A method for screening candidate antimicrobial compounds is described that utilizes a human vaginal xenograft engrafted in a non-human host. The method may be performed by using pathogen inoculated human vaginal xenografts in order to screen a wide range of candidate antimicrobials administered topically or systemically.

Claims

1. A method for screening compounds, comprising:

a) providing;

i) an immunocompromised non-human host;

ii) a human vaginal graft comprising a lumen;

iii) a candidate compound; and

iv) a pathogen;

b) engrafting said vaginal graft within said host to create an engrafted vaginal xenograft comprising a lumen;

c) introducing said compound systemically into said non-human host;

d) inoculating said engrafted vaginal xenograft with said pathogen; and

e) testing said engrafted vaginal xenograft for the presence of pathogen.

2. The method of claim 1, wherein said inmuunocompromised non-human host is a vertebrate.

3. The method of claim 1, wherein said human vaginal graft comprises a split thickness graft.

4. The method of claim 3, wherein said split thickness graft was configured to create a lumen, wherein said lumen is substantially lined with epithelial cells.

5. The method of claim 1, wherein said pathogen is selected from bacteria, fungi, parasites, and viruses.

6. The method of claim 5, wherein said viruses are selected from the group consisting of HSV-2, HPV, and HIV.

7. The method of claim 1, wherein, after said engrafting of step (b), said host is administered one or more gonadal hormones.

8. A method for screening compounds, comprising:

a) providing;

i) an immunocompromised non-human host;

ii) a human vaginal graft comprising a lumen;

iii) a candidate compound; and

iv) a pathogen;

b) engrafting said vaginal graft within said host to create an engrafted vaginal xenograft comprising a lumen;

c) inoculating said engrafted vaginal xenograft with said pathogen;

d) introducing said compound systemically into said non-human host; and

e) testing said engrafted vaginal xenograft for the presence of pathogen.

9. The method of claim 8, wherein said immunocompromised non-human host is a vertebrate.

10. The method of claim 8, wherein said human vaginal graft comprises a split thickness graft.

11. The method of claim 10, wherein said split thickness graft was configured to create a lumen, wherein said lumen is substantially lined with epithelial cells.

12. The method of claim 8, wherein said pathogen is selected from bacteria, fungi, parasites, and viruses.

13. The method of claim 12, wherein said viruses are selected from the group consisting of HSV-2, HPV, and HIV.

14. The method of claim 8, wherein, after said engrafting of step (b), one or more gonadal hormones is administered to said host.

15. The method of claim 14, wherein said hormone is selected from the group consisting of β

-estradiol and progesterone.