Systems and methods for isolating and using clinically safe adipose derived regenerative cells

• US 20050260175A1
• Filed: 07/02/2004
• Published: 11/24/2005
• Est. Priority Date: 12/07/2001
• Status: Active Grant

• Current Assignee: Lorem Vascular Pte. Ltd.
• Original Assignee: Cytori Therapeutics Incorporated
• Inventors: Fraser, John K., Hedrick, Marc H., Wulur, Isabella, Schulzki, Michael J., Carlson, Grace, Schreiber, Ronda Elizabeth, Byrnes, Bobby
• Granted Patent: US 7,585,670 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61B 17/00 Surgical instruments, devices or methods, e.g. tourniquets A61B18/00 takes precedence; contraceptive devices, pessaries, or applicators therefor A61F6/00; eye surgery A61F9/007; ear surgery A61F11/00
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: C12M 29/04 Filters; Permeable or porous membranes or plates, e.g. dialysis
• CPC Class Codes: C12M 45/00 Means for pre-treatment of biological substances
• CPC Class Codes: C12M 47/04 Cell isolation or sorting purging biological preparations of unwanted cells C12N5/0081, determining the presence or kind of microorganism C12Q1/04
• CPC Class Codes: C12N 5/0667 Adipose-derived stem cells [ADSC]; Adipose stromal stem cells

Abstract

Systems and methods are described that are used to separate cells from a wide variety of tissues. In particular, automated systems and methods are described that separate regenerative cells, e.g., stem and/or progenitor cells, from adipose tissue. The systems and methods described herein provide rapid and reliable methods of separating and concentrating regenerative cells suitable for re-infusion into a subject.

Claims

1. A method for inducing hard or soft tissue formation, comprising:

(1) concentrating regenerative cells from tissue to form a composition, at least part of the composition being tested not to provoke an adverse event in a patient; and

(2) placing the composition in the patient to induce hard or soft tissue formation.

2. An apparatus constructed to perform the concentrating and testing steps of claim 1.

3. A composition formed according to the concentrating and testing steps of claim 1.

4. The method of claim 1, wherein the testing is performed automatically prior to the placing.

5. The method of claim 4, wherein the testing comprises:

receiving an input identifying at least one of a type of implantation to be performed and the type of hard or soft tissue formation to be induced;

selecting a plurality of tests from a stored group of tests, based upon the input; and

communicating the selected tests to a user.

6. The method of claim 5, wherein the testing of at least part of the composition is performed automatically prior to the placing.

7. The method of claim 4, wherein the testing comprises:

receiving an input identifying at least one of a type of implantation to be performed and the type of hard or soft tissue formation to be induced;

selecting at least one test from a plurality of tests; and

performing the at least one test on at least part of the composition, based upon the input.

8. The method of claim 7, wherein the testing of at least part of the composition is performed automatically prior to the placing.

9. The method of claim 7, wherein:

the selecting comprises selecting multiple tests and is followed by indicating to a user the selected tests, and

the performing of the at least one test is preceded by receiving an input from the user to perform the at least one test.

10. The method of claim 9, wherein the at least one test, which is input from the user, is one of the multiple tests.

11. An apparatus constructed to perform the method of claim 7.

12. The method of claim 7, wherein:

the placing comprises intravascular delivery of at least part of the composition into the patient, and

at least part of the composition is tested for clinically unsafe levels of at least one of endotoxins, residual enzymes which may have been introduced during the concentrating, free lipid, and agonists of platelet aggregation.

13. The method of claim 7, wherein:

the placing comprises a non-systemic implantation of at least part of the composition into the patient, and

the composition comprises agonists of platelet aggregation.

14. The method of claim 7, wherein:

the placing comprises a non-systemic implantation of at least part of the composition into the patient, and

the composition comprises free lipid.

15. An apparatus constructed to perform the concentrating and testing steps of claim 1, wherein the testing comprises:

receiving an input identifying at least one of a type of implantation to be performed and the type of hard or soft tissue formation to be induced;

selecting at least one test from a plurality of tests; and

performing the test on at least part of the composition, based upon the input.

16. An apparatus constructed to automatically perform the concentrating and testing steps of claim 1, and further to automatically:

receive an input identifying at least one of a type of implantation to be performed and the type of hard or soft tissue formation to be induced;

select at least one test from a plurality of tests; and

perform the at least one test on at least part of the composition, based upon the input.

17. The apparatus of claim 16, wherein:

the type of implantation to be performed is a non-systemic implantation; and

the concentrating comprises only partially disaggregating the tissue.

18. The apparatus of claim 17, wherein the at least one selected test does not include a test for free lipids.

19. An apparatus constructed to automatically perform the concentrating and testing steps of claim 1’

, and further to automatically;

receive an input identifying at least one of a type of implantation to be performed and the type of hard or soft tissue formation to be induced;

select a plurality of tests from a stored group of tests, based upon the input; and

communicate the selected tests to a user.

20. The apparatus of claim 19, wherein:

the type of implantation to be performed is a non-systemic implantation; and

the concentrating comprises only partially disaggregating the tissue.

21. The apparatus of claim 20, wherein the selected plurality of tests does not include a test for free lipids.

22. The method of claim 1, wherein at least part of the composition is tested for clinically unsafe levels, relative to the hard or soft tissue formation to be induced in (2), of at least one of endotoxins, residual enzymes which may have been introduced during the concentrating, free lipid, and residual extracellular matrix which may be present from the concentrating.

23. The method of claim 22, wherein:

the placing comprises intravascular or systemic delivery of at least part of the composition into the patient; and

the testing comprises testing for levels of residual proteolytic enzyme activity from enzymes used in the concentrating that would be likely to provoke an adverse event in the patient following the placing.

24. The method of claim 22, wherein:

the placing comprises intravascular or systemic delivery of at least part of the composition into the patient; and

the testing comprises testing for levels of free lipid that would be likely to provoke an adverse event in the patient following the placing.

25. The method of claim 22, wherein:

the placing comprises intravascular or systemic delivery of at least part of the composition into the patient; and

the testing comprises testing for levels of agonists of platelet aggregation including collagen fragments that would be likely to provoke an adverse event in the patient following the placing.

26. The method of claim 22, wherein substantially all non-biologic that contacts the tissue during and after the concentrating is tested before the concentrating to contain ≦

about 20.0 United States Pharmacopeia (USP) endotoxin units (EU)/device.

27. The method of claim 22, wherein the testing is performed automatically prior to the placing.

28. The method of claim 1, wherein the concentrating comprises only partially disaggregating the tissue.

29. The method of claim 28, wherein the disaggregating is performed with one or more enzymes, which are removed from at least a part of the tissue early, relative to an amount of time that the enzyme would otherwise be left thereon to fully disaggregate the tissue.

30. The method of claim 28, wherein the tissue comprises adipose tissue.

31. The method of claim 1, wherein the concentrating comprises providing an automated system comprising:

a. a chamber assembly to receive tissue removed from a patient, wherein the chamber assembly facilitates disaggregation of the tissue such that regenerative cells are separated from the tissue;

b. a concentration device which can be connected to concentrate regenerative cells from the chamber assembly; and

c. a programmable processing device capable of communicating with and controlling the chamber assembly and the concentration device.

32. The method of claim 31, wherein the concentration device comprises a centrifugation device.

33. The method of claim 31, wherein the chamber assembly comprises a collection chamber and a processing chamber.

34. The method of claim 33, wherein:

the providing comprises coupling the processing chamber to the collection chamber; and

the centrifugation device is configured to connect with and receive the disaggregated tissue from the collection chamber.

35. The system of claim 1, wherein the tissue is adipose tissue.

36. The system of claim 1, wherein the regenerative cells are stem cells.

37. The system of claim 1, wherein the regenerative cells are progenitor cells.

38. The system of claim 1, wherein the regenerative cells are a combination of stem cells and progenitor cells.