Granted Patent
B2
US 12,569,517 · App. 17/429,553 · Granted Mar 10, 2026
Method for treating osteoarthritis with mesenchymal stem cell exosomes
Assignee:
Direct Biologics, LLC
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Abstract
Disclosed herein are methods for treating osteoarthritis may be a one-step arthroscopic procedure and may include detaching synovial mesenchymal stem cells (MSCs) from the synovium using a brush device; covering articular cartilage in an affected joint with a scaffold; and placing concentrated MSC exosomes into the affected joint to stimulate differentiation of synovial MSCs into articular cartilage cells.
Claims (20)
1 . A method of treating osteoarthritis in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of a mesenchymal stem cell (MSC) exosome composition comprising (i) MSC exosomes; (ii) an insulin-like growth factor (IGF) and (iii) vascular endothelial growth factor (VEGF).
2 . The method of claim 1 , wherein the osteoarthritis affects one or more joints, wherein the one or more joints comprise one or more of the ankle, knee, hip, wrist, elbow, shoulder, knuckle, and neck.
3 . The method of claim 2 , wherein the MSC exosome composition is administered to each joint affected by the osteoarthritis.
4 . The method of claim 1 , wherein the MSC exosome composition is administered via injection, the MSC exosome composition is administered with a scaffold, or the MSC exosome composition is administered in a hydrogel, topical cream, or salve.
5 . The method of claim 1 , further comprising preparing the MSC exosome composition prior to the administering, the preparing comprising: (a) culturing a bone marrow-derived mesenchymal stem cell (bmMSC) at about 0.1% to about 2% oxygen to generate a conditioned medium comprising the MSC exosome composition; and (b) isolating the MSC exosome composition.
6 . The method of claim 5 , wherein culturing the bmMSC occurs at a pH of about 6.2 to about 7.4.
7 . The method of claim 5 , wherein the bmMSC is a human bmMSC.
8 . The method of claim 1 , wherein the MSC exosome composition comprises saline.
9 . The method of claim 1 , wherein the MSC exosome composition comprises MSC exosomes having a size of about 35 to about 150 nm.
10 . The method of claim 1 , wherein the exosome composition comprises exosomes having a size of about 35 to about 150 nm.
11 . The method of claim 1 , wherein the exosome composition further comprises a therapeutically effective amount of hepatocyte growth factor (HGF), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), bone morphogenetic protein 5 (BMP5), orepidermal growth factor (EGF), or a combination of two or more thereof.
12 . The method of claim 1 , wherein the exosome composition further comprises a a therapeutically effective amount of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), IL-1 receptor antagonist, bone morphogenetic protein (BMP), granulocyte colony stimulating factor (G-CSF), or granulocyte macrophage colony stimulating factor (GM-CSF), or a combination of two or more thereof.
13 . The method of claim 1 , wherein the MSC exosome composition further comprises a cryoprotectant oligosaccharide and/or a biocompatible polymer.
14 . The method of claim 1 , wherein the MSC exosome composition further comprises a a therapeutically effective amount of bone morphogenetic protein (BMP).
15 . The method of claim 1 , wherein the MSC exosome composition further comprises a a therapeutically effective amount of macrophage colony stimulating factor (M-CSF).
16 . The method of claim 1 , wherein the MSC exosome composition further comprises a a therapeutically effective amount of transforming growth factor p1 (TGF-31).
17 . The method of claim 1 , wherein the MSC exosome composition further comprises a a therapeutically effective amount of granulocyte macrophage colony stimulating factor (GM-CSF).
18 . The method of claim 1 , wherein the MSC exosome composition further comprises a a therapeutically effective amount of interleukin-4 (IL-4), interleukin-10 (IL-10), or bone morphogenetic protein 5 (BMP5), or a combination of two or more thereof.
19 . The method of claim 1 , wherein the MSC exosome composition further comprises a a therapeutically effective amount of IL-1 receptor antagonist, fibroblast growth factor-1 (FGF 1), fibroblast growth factor-2 (FGF2), platelet derived growth factor (PDGF), macrophage colony stimulating factor (M-CSF), or granulocyte colony stimulating factor (G-CSF), or a combination of two or more thereof.
20 . The method of claim 1 , wherein the MSC exosome composition further comprises a a therapeutically effective amount of prostaglandin E2 (PGE2), transforming growth factor p1 (TGF-31), hepatocyte growth factor (HGF), stromal cell derived factor-1 (SDF-1), indoleamine 2,3-dioxygenase, interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), IL-1 receptor antagonist, soluble TNF-α receptor, fibroblast growth factor-1 (FGF1), fibroblast growth factor-2 (FGF2), bone morphogenetic protein (BMP), bone morphogenetic protein 5 (BMP5), epidermal growth factor (EGF), transforming growth factor-a (TGF-a), platelet derived growth factor (PDGF), macrophage colony stimulating factor (M-CSF), insulin, granulocyte colony stimulating factor (G-CSF), or granulocyte macrophage colony stimulating factor (GM-CSF), or a combination of two or more thereof.
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 6, 2026
From: MOSELEY, TIMOTHY ALEXANDER
To: DIRECT BIOLOGICS, LLC
Reel/Frame 073719/0108 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 24, 2025
From: PETTINE, KENNETH ALLEN
To: DIRECT BIOLOGICS, LLC
Reel/Frame 072925/0519 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 21, 2023
From: PETTINE, KENNETH ALLEN; MOSELEY, TIMOTHY ALEXANDER
To: DIRECT BIOLOGICS LLC
Reel/Frame 064013/0071 →
Continuity (3)
Provisional Application
62908853
· Oct 1, 2019
Provisional Application
62802310
· Feb 7, 2019
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