Ex vivo methods for testing organ system disruption

• US 20080288399A1
• Filed: 05/18/2007
• Published: 11/20/2008
• Est. Priority Date: 05/18/2007
• Status: Active Grant

• Current Assignee: Lifeline Scientific, Inc. (Shanghai Genext Medical Technology Co., Ltd.)
• Original Assignee: Lifeline Scientific, Inc. (Shanghai Genext Medical Technology Co., Ltd.)
• Inventors: Brassil, John, Kravitz, David, Curtis, Christopher Gerald
• Granted Patent: US 8,771,930 B2
• Time in Patent Office: Days
• US Class Current: 705/40
• CPC Class Codes: G01N 33/5014 for testing toxicity
• CPC Class Codes: G01N 33/5082 Supracellular entities, e.g. tissue, organisms
• CPC Class Codes: G01N 33/566 using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: G06Q 20/102 Bill distribution or payments

Abstract

Properties such as toxicity of substances may be determined by assaying properties, fates and effects of substances in an ex vivo metabolically active human organ or tissue under normothermic perfusion with a fluid containing a test substance. The data can be used as, for example, part of a submission to a government regulatory organization. Preferred methods use perfused endocrine gland organs or tissues to evaluate hormone or other bodily chemical disruption caused by substances and pre-donation diseased or injured organs or tissues.

Claims

1. A method of testing the toxicity of a substance, comprising:

passing a perfusate comprising the substance under normothermic conditions through at least one metabolically active ex vivo donated human organ or tissue that was injured or diseased before donation;

collecting data derived from the perfused organ or tissue; and

analyzing the data to assess toxicity of the substance.

2. The method of claim 1, wherein the data are used to analyze at least one of the following:

hormone level, target cell-receptor mediation, glandular secretion function, hormone function, organ function and a combination thereof.

3. The method of claim 1, wherein the data are collected by electrophysiological testing, medical diagnostic imaging, spectroscopic testing, microdialysis, solid state tissue probe testing or a combination thereof.

4. The method of claim 1, wherein the organ or tissue is selected from the group consisting of endocrine glands and exocrine glands.

5. The method of claim 1, wherein the organ or tissue is an organ selected from the group consisting of pancreas, thymus, male reproductive organs, female reproductive organs, thyroid gland and adrenal gland.

6. The method of claim 1, wherein the passing comprises perfusing the organ or tissue with a first perfusate that does not contain the substance, followed by perfusing the organ or tissue with a second perfusate that contains the substance.

7. The method of claim 1, wherein the organ or tissue has been injured by mechanical injury.

8. The method of claim 1, wherein the organ or tissue is diseased.

9. The method of claim 1, wherein the data are analyzed to assess whether a hormone level is unaltered or is increased, decreased or otherwise altered.

10. The method of claim 1, wherein said substance is a substance other than a drug or drug candidate.

11. The method of claim 1, wherein said substance is selected from the group consisting of agricultural products, industrial products, building materials, food products, tobacco products, cleaning products and cosmetics.

12. A method of generating revenue, comprising:

charging a fee to a third party for collecting data relating to the toxicity of a test substance;

passing a perfusate comprising the substance under normothermic conditions through at least one metabolically active ex vivo donated human organ or tissue that was injured or diseased before donation;

collecting data derived from the perfused organ or tissue; and

providing information relative to the data to said third party.

13. The method of claim 12, wherein the data are provided to said third party in a raw form.

14. The method of claim 12, further comprising conducting an analysis of the data and providing results of said analysis to the third party.

15. A method of testing the toxicity of a substance, comprising:

passing a perfusate comprising the substance under normothermic conditions through at least one metabolically active ex vivo human endocrine gland or endocrine gland tissue under normothermic conditions;

collecting data derived from the perfused organ or tissue; and

analyzing the data to assess effects of the substance on hormone uptake or production by said organ or tissue.

16. The method of claim 15, wherein the organ or tissue is a donated organ or tissue from a human being.

17. The method of claim 15, wherein the organ or tissue is an engineered organ or tissue derived from isolated and/or cultured human cells.

18. The method of claim 15, wherein the data are collected by electrophysiological testing, medical diagnostic imaging, spectroscopic testing, microdialysis, solid state tissue probe testing or a combination thereof.

19. The method of claim 15, wherein the endocrine gland is selected from the group consisting of pancreas, thymus, male reproductive organs, female reproductive organs, thyroid gland and adrenal gland.

20. The method of claim 15, wherein the organ or tissue is diseased or injured.

21. The method of claim 15, wherein the organ or tissue has been injured by prolonged warm ischemia.

22. The method of claim 15, wherein the organ or tissue has been injured by prolonged hypothermic storage.

23. The method of claim 15, wherein the organ or tissue has been injured by mechanical injury.

24. The method of claim 15, wherein the organ or tissue is diseased.

25. The method of claim 15, wherein the data are analyzed to assess whether a hormone level is unaltered or is increased, decreased or otherwise altered.

26. The method of claim 15, wherein said substance is a substance other than a drug or drug candidate.

27. The method of claim 15, wherein said substance is a drug or drug candidate.

28. The method of claim 15, wherein said substance is selected from the group consisting of agricultural products, industrial products, building materials, food products, tobacco products, cleaning products and cosmetics.

29. A method of generating revenue, comprising:

charging a fee to a third party for collecting data relating to the toxicity of a test substance;

passing a perfusate comprising the substance under normothermic conditions through at least one metabolically active ex vivo human endocrine gland or endocrine gland tissue under normothermic conditions;

collecting data derived from the perfused organ or tissue relating to hormone uptake or production; and

providing information relative to the data to said third party.

30. The method of claim 29, wherein the data are provided to said third party in a raw form.

31. The method of claim 29, further comprising conducting an analysis of the data and providing results of said analysis to the third party.