Compositions and methods to promote implantation and engrafment of stem cells

• US 8,871,199 B2
• Filed: 11/26/2012
• Issued: 10/28/2014
• Est. Priority Date: 12/19/2007
• Status: Active Grant

• Current Assignee: Regenexx LLC
• Original Assignee: Regenerative Sciences, Llc
• Inventors: Centeno, Christopher J.
• Primary Examiner(s): Palenik, Jeffrey T
• Application Number:
  US13/685,527
• Publication Number:
  US 20130084341A1
• Time in Patent Office: 701 Days
• Field of Search: None
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/7004 Monosaccharides having only carbon, hydrogen and oxygen atoms
• 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 38/19 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 38/363 Fibrinogen
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Tissue repair in-vivo depends on acute inflammation, but in many clinical situations the other major components of healing such as blood supply, anabolic hormones, growth factors, and stem cells are lacking. This invention includes compositions consisting of an agent which induces an inflammatory healing response combined with an autologous platelet lysate at a specific concentration which may have demonstrated in-vitro abilities to expand autologous tissue repair cells.

Claims

1. A method for facilitated tissue repair in a subject in need thereof comprising:

obtaining platelets from the subject;

preparing a 5% to 40% platelet lysate solution from the platelets;

administering a hyper osmolar agent to the subject in an amount sufficient to induce local inflammation at the site in need of tissue repair; and

subsequently and non-contemporaneously administering a composition comprising the 5% to 40% platelet lysate solution to the subject at the site in need of tissue repair;

wherein tissue repair is facilitated at the site in the subject in need of tissue repair.

2. The method of claim 1, further comprising obtaining mesenchymal stem cells (MSC) from the patient and expanding the MSC in culture, wherein the composition further comprises the patient'"'"'s expanded MSC.

3. The method of claim 1, where administering to the patient is to the site in need of repair through a surgical incision, arthroscopically or percutaneously.

4. The method of claim 1, wherein cytokines are added to the 5% to 40% platelet lysate solution in amount sufficient to alter the timing of growth factor degranulation off of platelets in the platelet lysate solution.

5. The method of claim 1, wherein the composition further comprises one or more essential nutrients wherein the essential nutrients are capable of further facilitating tissue repair.

6. The method of claim 5, wherein the one or more essential nutrients is selected from the group consisting of glycoaminosglycans, collagen, amino acids, peptides, proteins, sodium pyruvate, glucose, glutamine, ribonucleosides, deoxyribonucleosides, carbohydrates, and essential oils.

7. The method of claim 1, wherein the composition further comprises one or more anabolic hormones.

8. The method of claim 1, wherein the inflammation inducing agent is formulated as a gel, hydrogel, or foam and the formulation localizes the micro-injury to the area of application.

9. The method of claim 1, wherein the site in need of tissue repair is cartilage of a joint.

10. The method of claim 9, wherein the joint is the knee joint.

11. The method of claim 1, wherein the non-contemporaneously administered composition comprising 5% to 40% platelet lysate solution is administered 3-5 days after the administration of the hyper osmolar agent.