Pharmaceutical kits comprising mesenchymal stem cells

• US 8,178,084 B2
• Filed: 09/08/2003
• Issued: 05/15/2012
• Est. Priority Date: 09/07/2002
• Status: Active Grant

• Current Assignee: Recellerate Inc.
• Original Assignee: Quy Biosciences Limited
• Inventors: Smith, Roger Kenneth Whealands, McGarrell, Kenneth Gregory, Goodship, Allen Edward, Blunn, Gordon William
• Primary Examiner(s): BERTOGLIO, VALARIE E
• Application Number:
  US10/526,753
• Publication Number:
  US 20060130852A1
• Time in Patent Office: 3,172 Days
• Field of Search: 424/93.1
• US Class Current: 424/93.1
• CPC Class Codes: A61K 35/16 Blood plasma; Blood serum umbilical cord blood A61K35/51
• CPC Class Codes: A61K 35/19 Platelets; Megacaryocytes
• 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: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 35/33 Fibroblasts
• CPC Class Codes: A61K 35/51 Umbilical cord; Umbilical cord blood; Umbilical stem cells
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue

Abstract

A method of treating a natural soft skeletal tissue injury in a patient the method comprising administering to the patient a composition of mesenchymal stem cells in liquid suspension enriched compared to the natural source of said cells, or tenocytes derived therefrom. The method is particularly suited to the regeneration of tendons in competitive mammals, such as the superficial digital flexor tendon of the horse.

Claims

1. A method of treating a soft skeletal tissue injury in a patient, wherein the soft skeletal tissue injury is a tendon or ligament injury, the method comprising:

isolating bone marrow cells comprising mesenchymal stem cells and culturing the bone marrow cells in vitro to generate a composition enriched for mesenchymal stem cells and administering to the tendon or ligament injury of the patient the composition enriched for mesenchymal stem cells in a liquid suspension of bone marrow supernatant, wherein said administering promotes regeneration of the tendon or ligament at the site of the tendon or ligament injury.

2. The method according to claim 1 wherein the soft skeletal tissue injury is strain induced.

3. The method according to claim 1 wherein the patient is a mammal.

4. The method according to claim 3 wherein the mammal is a human or a non-human mammal.

5. The method according to claim 4 wherein the non-human mammal is selected from the group consisting of horses, dogs and camels.

6. The method according to claim 1 wherein the patient is a horse.

7. The method according to claim 1 wherein the patient is a horse or a camel and the soft skeletal tissue is selected from the group consisting of superficial digital flexor tendon (SDFT), suspensory ligament, deep digital flexor tendon, cruciate ligament, and accessory ligament of the deep digital flexor tendon.

8. The method according to claim 1 wherein the patient is a dog and the soft skeletal tissue is selected from the group consisting of Achilles tendon, cruciate ligament, and flexor tendon.

9. The method according to claim 1 wherein the patient is a human and the soft skeletal tissue is selected from the group consisting of Achilles tendon, quadriceps tendon, rotator cuff, medial and lateral epicondylitis, and cruciate ligament.

10. The method according to claim 1 wherein the mesenchymal stem cells are allogenic.

11. The method according to claim 1 wherein the mesenchymal stem cells are autologous.

12. The method according to claim 11 wherein the mesenchymal stem cells are derived from bone marrow of the patient.

13. The method according to claim 1 wherein the liquid suspension of mesenchymal stem cells is injected.

14. The method according to claim 1 wherein the tendon or ligament injury is cleansed of damaged tissue and any early repair scar tissue starting to form at the tendon or ligament injury before administration of the composition of mesenchymal stem cells.

15. The method according to claim 1 wherein the soft skeletal tissue injury comprises a cavity, or a lesion that can be closed to form a cavity, for retaining the composition.

16. The method according to claim 1 wherein the composition comprises a gelling agent.

17. The method of claim 1, wherein the soft skeletal tissue injury is percutaneous or subcutaneous.

18. The method of claim 1, wherein the soft skeletal tissue injury is a natural subcutaneous strain induced injury in a tendon or ligament selected from the group consisting of superficial digital flexor tendon (SDFT), suspensory ligament, deep flexor tendon, deep digital flexor tendon (DDFT), accessory ligament of the deep digital flexor tendon, cruciate ligament, Achilles tendon, flexor tendon, quadriceps tendon, rotator cuff, and lateral or medial epichondylitis.

19. A method of treating a soft skeletal tissue injury in a patient, wherein the soft skeletal tissue injury is a tendon or ligament injury, the method comprising:

isolating a bone marrow aspirate comprising bone marrow cells;

culturing the bone marrow cells in vitro to generate a composition comprising an enriched concentration of mesenchymal stem cells in liquid suspension media, wherein the enriched concentration of mesenchymal stem cells is at least two-fold enriched relative to that of the bone marrow aspirate; and

administering the composition comprising the enriched concentration of mesenchymal stem cells to the tendon or ligament injury of the patient, wherein said administering promotes repair of the tendon or ligament at the site of the tendon or ligament injury.

20. The method of claim 19, wherein the liquid suspension media comprises one or more of platelet rich plasma, bone marrow supernatant, serum, plasma, growth factors, differentiation factors, regeneration factors, cytokines or cartilage oligomeric matrix protein.

21. The method of claim 19, wherein the mesenchymal stem cells are enriched in vitro by at least one passage of the bone marrow cells in culture.

22. The method of claim 20, wherein the liquid suspension media comprises plasma or serum with the addition of one or more growth factors, differentiation factors or regeneration factors.

23. The method of claim 22, wherein the additional growth factors, differentiation factors or regeneration factors comprise one or more of TGF beta, IGF 1, IGF 2, PDGF, FGF, or COMP.