Method for treating osteoarthritis with mesenchymal stem cell exosomes
Inventors
Pettine, Kenneth Allen • MOSELEY, Timothy Alexander
Assignees
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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.
Core Innovation
The invention provides a method of treating osteoarthritis in a subject in need thereof by administering a therapeutically effective amount of an MSC exosome composition. The MSC exosome composition includes MSC exosomes together with insulin-like growth factor (IGF) and vascular endothelial growth factor (VEGF), and the description also characterizes the composition as including additional bioactive factors and sterility.
The invention addresses osteoarthritis problems through synovitis, inflammation, and pain mechanisms associated with osteoarthritis. The description links osteoarthritis pathology to inflammation and synovial dysfunction and positions exosome-based paracrine signaling as a way to modulate synovial inflammation. The claimed composition is described as delivering anti-inflammatory growth factors and exosomal RNA that can modulate synovial inflammation.
The invention further supports local treatment concepts by describing administration of the MSC exosome composition in formats such as injection, scaffold, hydrogel, or topical cream or salve. The description also relates treatment to synovium-derived MSCs and scaffold-supported differentiation concepts to enhance synovial MSC differentiation toward articular cartilage cells. Documented examples in the description report symptom and function improvements with imaging follow-up.
Claims Coverage
The independent claim set includes one independent method claim covering treatment of osteoarthritis by administering a therapeutically effective MSC exosome composition that contains MSC exosomes plus IGF and VEGF. The dependent claims refine this core by adding constrained exosome size, additional cytokines and growth factors, formulation and/or preparation constraints, and specific administration modalities and carriers.
Administering MSC exosomes with IGF and VEGF for osteoarthritis treatment
Administering to the subject a therapeutically effective amount of a mesenchymal stem cell (MSC) exosome composition comprising MSC exosomes, an insulin-like growth factor (IGF), and vascular endothelial growth factor (VEGF).
Therapeutically effective MSC exosome composition with constrained exosome size
The method includes using an exosome composition where the exosomes have a size of about 35 to about 150 nm.
Therapeutically effective MSC exosome composition with additional cytokines and growth factors
The method further includes an exosome composition containing a therapeutically effective amount of one or more specified cytokines and growth factors, or combinations thereof, including hepatocyte growth factor (HGF), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), bone morphogenetic protein 5 (BMP5), and orepidermal growth factor (EGF).
Preparation by culturing to generate conditioned medium and isolating the MSC exosome composition
Preparing the MSC exosome composition by culturing bone marrow-derived mesenchymal stem cells at about 0.1% to about 2% oxygen to generate conditioned medium comprising the MSC exosome composition and isolating the MSC exosome composition before administration.
Administration with injection plus scaffold or within hydrogel or topical composition
Specifying administering the MSC exosome composition by injection together with a scaffold, or within a hydrogel, topical cream, or salve.
MSC exosome composition formulated with a cryoprotectant oligosaccharide and/or biocompatible polymer
The MSC exosome composition includes a cryoprotectant oligosaccharide and/or a biocompatible polymer.
Overall, the claim coverage is centered on osteoarthritis treatment via local administration of an MSC exosome composition containing IGF and VEGF, with dependent claim refinements covering exosome size constraints, optional addition of specific cytokines/growth factors, preparation by oxygen-conditioned culturing and isolation, formulation additives, and specified administration modalities such as scaffold/hydrogel/topical compositions.
Stated Advantages
Improvement in symptoms and function for osteoarthritis subjects as reported in case examples.
MRI follow-up without worsening or complications as reported in the description.
Documented Applications
Treating osteoarthritis in multiple joints described in case examples, including hip, shoulder, elbow, and knee/other joints, with symptom/function improvements and MRI follow-up.
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