Renovation and repopulation of decellularized tissues and cadaveric organs by stem cells

• US 20020160510A1
• Filed: 02/13/2002
• Published: 10/31/2002
• Est. Priority Date: 02/14/2001
• Status: Active Grant

• Current Assignee: Celularity, Inc.
• Original Assignee: Anthrogenesis Corporation (Bristol-Myers Squibb Company)
• Inventors: Hariri, Robert J.
• Granted Patent: US 7,311,904 B2
• Time in Patent Office: Days
• US Class Current: 435/368
• 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: A61K 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 27/3695 characterised by the function or physical properties of the final product, where no specific conditions are defined to achieve this A61L27/3687, A61L27/3691 take precedence
• 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: A61M 1/02 Blood transfusion apparatus blood infusion by syringes A61M5/14
• CPC Class Codes: A61M 2202/0462 Placental blood, umbilical cord blood
• CPC Class Codes: A61M 2210/1458 Placenta
• CPC Class Codes: A61M 2210/1466 Umbilical cord
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C12N 2509/00 Methods for the dissociation of cells, e.g. specific use of enzymes
• CPC Class Codes: C12N 2513/00 3D culture
• CPC Class Codes: C12N 2533/90 Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0605 Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
• CPC Class Codes: C12N 5/0606 Pluripotent embryonic cells, e.g. embryonic stem cells [ES] embryonic germ cells C12N5/0611, induced pluripotent stem cells C12N5/0696
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12N 5/0678 Stem cells; Progenitor cells; Precursor cells

Abstract

A method of manufacturing a tissue matrix for implantation into a patient is disclosed. The method sets forth collecting embryonic stem cells from a placenta which has been treated to remove residual cord blood and seeding the collected stem cells onto or into a tissue matrix. The seeded tissue matrix is then implanted on or into a patient. The seeded tissue matrix made by the method of the present invention is also disclosed.

Claims

1. A method of manufacturing a tissue matrix for implantation into a patient, comprising:

collecting embryonic stem cells from a placenta which has been treated to remove residual cord blood and

seeding said collected stem cells onto or into a tissue matrix for implantation into a patient.

2. The method of claim 1 further comprising perfusing a placenta which has been drained of cord blood with an anticoagulant solution to flush out residual cells and collecting said residual cells and perfusion liquid from the drained placenta for seeding into or onto the tissue matrix.

3. The method of claim 2 further comprising separating said embryonic stem cells from said residual cells and perfusion liquid prior to seeding the tissue matrix.

4. The method of claim 1 including wherein the placenta is perfused with the anticoagulant solution by passing the anticoagulant solution into one or both of the umbilical artery and umbilical vein.

5. The method of claim 1 including wherein said residual cells and perfusion liquid are collected from the part of the placenta that was attached to the wall of the uterus of the mother.

6. The method of claim 3 including wherein said embryonic stem cells are separated from said residual perfusion liquid by centrifugation.

7. The method of claim 1 including wherein the tissue matrix is a decellularized tissue.

8. The method of claim 7 including wherein said tissue matrix is washed to assure removal of cellular and extracellular debris prior to said seeding.

9. The method of claim 8 including wherein said tissue matrix prior to said seeding is treated with factors to enhance the adhesion of and inward migration of said embryonic stem cells.

10. The method of claim 1 including wherein the tissue matrix is formed of natural or synthetic polymers.

11. A seeded tissue matrix made by any one of the methods of claims 1-10.

12. A method of treating a patient to repair or replace tissue comprising:

implanting a seeded tissue matrix at a site of the patient'"'"'s body in need of treatment wherein said seeded tissue matrix is made by any one of the methods of claims 1-10.

14. The isolated mammalian placenta of claim 13 that has been stored after expulsion from the uterus of the mammalian.

15. The isolated mammalian placenta of claim 13 that has been incubated to allow for the production of cells therefrom.

17. The method of claim 16 including wherein said isolated mammalian placenta is incubated to allow for the production of embryonic-like cells from said isolated mammalian placenta.

18. An isolated placental stem cell produced by the method of claim 16.

19. An isolated placental stem cell produced by the method of claim 17.

20. A pharmaceutical composition comprising an isolated placental stem cell obtained by the method of claim 16.

21. A pharmaceutical composition comprising an isolated placental stem cell obtained by the method of claim 17.

22. The method of claim 1 including before seeding said collected stem cells onto or into said tissue matrix, stimulating said placenta with exogenous cells.

23. The method of claim 2 including before seeding said collected stem cells onto or into said tissue matrix, stimulating said placenta with exogenous cells.

13. An isolated mammalian placenta comprising a mammalian placenta that has been expelled from the body of the mammalian, exsanguinated and perfused with perfusion solution to obtain embryonic-like cells.

16. A method of culturing an isolated mammalian placenta comprising obtaining a placenta after expulsion from the uterus, exsanguinating the placenta, and perfusing the placenta to obtain said isolated mammalian placenta.