Macrophage cell therapy to treat orthopedic injury

Patent metadata

Field	Value
Publication number	US-11738046-B2
Application number	US-201816179298-A
Country	US
Kind code	B2
Filing date	Nov 2, 2018
Priority date	Nov 3, 2017
Publication date	Aug 29, 2023
Grant date	Aug 29, 2023

Abstract

An ex vivo generated population of tissue-specific alternatively-activated macrophages and methods of making and using such macrophages for treating orthopedic injury are provided.

First claim

We claim:

1. A method of treating an orthopedic injury to a ligament or a tendon in a subject in need thereof, the method comprising the step of:
administering directly to the injured ligament or tendon of the subject a population of cells comprising bone marrow exosome educated macrophages (BM-EEM),
wherein the BM-EEM comprise isolated peripheral CD14+ macrophages cultured with bone marrow mesenchymal stem cell-derived exosomes, and
wherein administration of the cells to the subject improves mechanical properties of the injured ligament or tendon.

2. The method of claim 1 , wherein the BM-EEM in the population are CD206 high, PD-L I high, PD-L2 high, TGF-high, TNF-a low, IL-6 high, and Serpine-1 high.

3. The method of claim 1 , wherein the population of cells is administered by injection.

4. The method of claim 3 , wherein the population of cells is administered by injection with a pharmaceutically acceptable carrier.

5. The method of claim 1 , wherein the population of cells is administered surgically.

6. The method of claim 1 , wherein the orthopedic injury to a ligament or a tendon is selected from the group consisting of a partial tendon tear, a complete tendon tear, a partial tendon laceration, a compete tendon laceration, a partial tendon avulsion, a complete tendon avulsion, a partial ligament tear, a complete ligament tear, a partial ligament laceration, a compete ligament laceration, tendinopathy, tendinosis, tendinitis, and joint capsule tears.

7. The method of claim 1 , wherein the orthopedic injury to a ligament or a tendon is selected from the group consisting of plantar fasciitis, tennis elbow, bicep tendinitis, and carpal tunnel syndrome.

8. The method of claim 1 , wherein the population of cells is administered at a dose between about 1×10 4 cells/kilogram and about 10×10 9 cells/kilogram of body weight of the subject.

9. A method of improving the mechanical properties of an injured ligament or tendon in a subject in need thereof, the method comprising the step of:
administering directly to the injured ligament or tendon of the subject a population of cells comprising bone marrow exosome educated macrophages (BM-EEM),
wherein the BM-EEM comprise isolated peripheral CD14+ macrophages cultured with bone marrow mesenchymal stem cell-derived exosomes; and
increasing at least one of Young's modulus and maximum stress of the injured ligament or tendon.

10. The method of claim 1 , wherein improvement in mechanical properties of the injured ligament or tendon is measurable by increases in at least one of Young's modulus and maximum stress of the injured ligament or tendon.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Hematti Peiman
• Chamberlain Connie
• Clements Anna Elizabeth Breiner
• Vanderby Ray
• Kink John A

Classifications

• A61K40/40

  characterised by antigens that are targeted or presented by cells of the immune system · CPC title

• A61K40/24

  Antigen-presenting cells [APC] · CPC title

• A61K40/17

  Monocytes; Macrophages · CPC title

• A61K9/0019 Primary

  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 title

• C12N5/0645

  Macrophages, e.g. Kuepfer cells in the liver; Monocytes · CPC title