Rapid preparation of stem cell matrices for use in tissue and organ treatment and repair

• US 20050220775A1
• Filed: 05/25/2005
• Published: 10/06/2005
• Est. Priority Date: 02/23/2001
• Status: Active Grant

• Current Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: University Of Pittsburgh (University of Pittsburgh of The Commonwealth System of Higher Education)
• Inventors: Sacks, Michael S., Chancellor, Michael B., Huard, Johnny, Chung, Steve, Capelli, Christopher
• Granted Patent: US 7,906,110 B2
• Time in Patent Office: Days
• US Class Current: 424/93.210
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61L 2430/22 for reconstruction of hollow organs, e.g. bladder, esophagus, urether, uterus
• CPC Class Codes: A61L 27/225 Fibrin; Fibrinogen
• CPC Class Codes: A61L 27/3629 Intestinal tissue, e.g. small intestinal submucosa
• CPC Class Codes: A61L 27/3679 Hollow organs, e.g. bladder, esophagus, urether, uterus, intestine
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 2533/56 Fibrin; Thrombin
• CPC Class Codes: C12N 2533/74 Alginate
• CPC Class Codes: C12N 2533/90 Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
• CPC Class Codes: C12N 2533/92 Amnion; Decellularised dermis or mucosa
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0658 Skeletal muscle cells, e.g. myocytes, myotubes, myoblasts
• CPC Class Codes: C12N 5/0668 Mesenchymal stem cells from other natural sources
• CPC Class Codes: C12N 5/0697 Artificial constructs associating cells of different lineages, e.g. tissue equivalents blood vessels C12N5/0691

Abstract

A rapid method for preparing stem cell and physiologically acceptable matrix compositions for use in tissue and organ repair is described. Compared with previous tissue engineering materials, the stem cell-matrix compositions of the present invention do not require long-term incubation or cultivation in vitro prior to use in in vivo applications. The stem cells can be from numerous sources and may be homogeneous, heterogeneous, autologous, and/or allogeneic in the matrix material. The stem cell-matrix compositions provide point of service utility for the practitioner, wherein the stem cells and matrix can be combined not long before use, thereby alleviating costly and lengthy manufacturing procedures. In addition, the stem cells offer unique structural properties to the matrix composition which improves outcome and healing after use. Use of stem cells obtained from muscle affords contractility to the matrix composition.

Claims

1. A rapid method of preparing a stem cell matrix for use in tissue and organ repair comprising:

a) admixing a preparation comprising stem cells with a physiologically acceptable matrix material to form a stem cell matrix; and

b) incubating the stem cell matrix in vitro for less than about 12 hours prior to use in tissue and organ repair or treatment.

2. The method according to claim 1, wherein the stem cells are autologous to a recipient.

3. The method according to claim 1, wherein the stem cells are allogeneic to a recipient.

4. The method according to claim 1, wherein the physiologically acceptable matrix material is absorbable.

5. The method according to claim 1, wherein the physiologically acceptable matrix material is non-absorbable.

6. The method according to claim 1, wherein the physiologically acceptable matrix material is selected from the group consisting of small intestine submucosa (SIS), crosslinked alginate, bioadhesives, hydrocolloid, collagen gel, collagen sponge, polyglycolic acid (PGA) mesh, polyglactin (PGL) mesh, fleeces, and dead de-epidermized skin equivalents.

7. The method according to claim 1, wherein the stem cells are homogeneous stem cells.

8. The method according to claim 1, wherein the stem cells are heterogeneous stem cells.

9. The method according to claim 1, wherein the stem cells are obtained from a tissue selected from the group consisting of adult, embryonic, and fetal tissue.

10. The method according to claim 1, wherein the tissue is bone marrow, muscle, adipose, liver, heart, lung, or nervous system tissue.

11. The method according to claim 1, wherein the stem cells are muscle stem cells.

12. The method according to claim 11, wherein the stem cell matrix is contractible.

13. The method according to claim 1, wherein about 2.5×

10³ to about 1×

10⁶ stem cells are admixed with the physiologically acceptable matrix material.

14. The method according to claim 1, wherein about 5×

10³ to about 1×

10⁶ stem cells are admixed with the physiologically acceptable matrix material.

15. The method according to claim 1, wherein about 1×

10⁵ stem cells are admixed per 1 cm² of the physiologically acceptable matrix material.

16. The method according to claim 1, wherein the stem cells are incubated with the physiologically acceptable matrix material in vitro for less than about 3 hours prior to use in tissue and organ repair.

17. The method according to claim 1, wherein the stem cells are incubated with the physiologically acceptable matrix material in vitro for less than about 1 hour prior to use in tissue and organ repair.

18. The method according to claim 1, wherein the stem cells are incubated with the physiologically acceptable matrix material in vitro for less than about 30 minutes prior to use in tissue and organ repair.

19. The method according to claim 1, wherein the stem cells are incubated with the physiologically acceptable matrix material in vitro from about 5 seconds to about 30 minutes prior to use in tissue and organ repair.

20. The method according to claim 1, wherein the stem cell matrix is used for wound healing, surgical incision repair, tissue augmentation, organ augmentation, smooth muscle repair, non-smooth muscle repair, or blood vessel repair.

21. The method according to claim 1, further comprising attaching the stem cells to the physiologically acceptable matrix material using a biological adhesive.

22. The method according to claim 21, wherein the biological adhesive is fibrin glue.

23. The method according to claim 1, further comprising applying the stem cell matrix to a tissue by spraying, painting, coating, or spreading.

24. The method according to claim 1, further comprising applying the stem cell matrix to an organ by spraying, painting, coating, or spreading.

25. A method of tissue and organ repair or treatment, comprising:

a) preparing a stem cell matrix by admixing a preparation comprising stem cells with a physiologically acceptable matrix;

b) incubating the stem cell matrix in vitro for less than about 12 hours prior to use; and

c) introducing the stem cell matrix into a patient.

26. A rapid method of preparing a stem cell matrix for use in tissue and organ repair comprising:

a) admixing a preparation comprising muscle stem cells with a physiologically acceptable matrix material to form a muscle stem cell matrix; and

b) incubating the muscle stem cell matrix in vitro for less than about 12 hours prior to use in tissue and organ repair or treatment.

27. A method of tissue and organ repair or treatment, comprising:

a) preparing a muscle stem cell matrix by admixing a preparation comprising muscle stem cells with a physiologically acceptable matrix;

b) incubating the muscle stem cell matrix in vitro for less than about 12 hours prior to use; and

c) introducing the muscle stem cell matrix into a patient.