What is regenerative medicine?
Branch of translational research which deals with the process of replacing, engineering, or regenerating human cells, tissues, or organs to restore normal function.
Do products currently available in veterinary medicine actually "regenerate" tissue during healing?
Remains unclear or unproven in many applications.
What are most currently available regenerative therapies aimed at?
1. Reducing inflammation
2. Promoting neovascularization
3. Modulating and promoting an anabolic local environment during healing.
What are currently available regenerative therapies NOT aimed at?
Direct regeneration of tissue via direct inoculation of a stem cell.
What is a better term than "regenerative therapies" for the therapies that are currently available?
Predominant indication in small and large animal medicine is the treatment of _____.
What 2 aspects of musculoskeletal disease are biological therapies most used for?
2. Tendon and ligament injury
What additional areas have ongoing research in veterinary medicine?
1. Pulmonary repair
2. Oncology and cancer therapy
What does IRAP mean/stand for?
Autologous Conditioned Serum
What does PRP stand for?
Platelet Rich Plasma
What does "pro-stride" mean?
Autologous Protein Solution
What are 4 locations from where we can get stem cells?
1. Bone marrow aspirate concentrate
2. Bone marrow-derived MSCs
3. Fat/Vascular Stromal Fraction MSCs
4. Autologous vs. Allogenic
What is autologous conditioned serum (IRAP) widely used for?
Equine sports medicine (for the last 15-20 years)
What does IRAP mainly use in its MOA?
What are cytokines and what are the 2 general types?
Proteins within mammals that are secreted by various cells of the immune system that influence an effect on another cell.
Types = Pro-inflammatory and Anti-inflammatory
What is the most common and central pro-inflammatory cytokine?
How is IL-1 involved in osteoarthritis?
It is upregulated in the joint and increases proteolytic enzymes (matrix metalloproteinases) which degrade type-2 collagen in articular cartilage.
What is one anti-inflammatory cytokine involved in IRAP and what is another name for it?
IL1-ra; AKA IRAP protein
Where does IL1-ra originate from?
monocyte cells in the blood
What does IL1-ra bind to and why?
Binds to IL-1 receptors to block cellular signaling of inflammation.
What does IL1-ra circulating in the blood do?
Normal amounts of circulating IL1-ra helps provide balance between anabolic (build/restore) and catabolic (breakdown) processes in the body.
IRAP binds to _____, preventing _____ binding which would cause _____.
IL-1 receptors, IL-1, inflammation
How do we capitalize on IL1-ra as a biological therapy?
Collect whole blood from animal. expose it to select surfaces to stimulate monocytes to secrete IL1-ra.
How can blood monocytes be stimulated to secrete IL1-ra?
1. Borosilicate or chromium sulfate glass beads in a syringe
2. Held at body temp (37.5 deg C) for up to 24 hours
3. Centrifuged and serum aspirated off
How much more IL1-ra vs. IL-1 does manipulated serum have at 24 hours (i.e. what is the IL1-ra to IL-1 ratio)?
6-10x more IL1-ra vs. IL1
How can autologous conditioned serum be used to influence inflammation?
It can be aseptically injected back into a joint compartment.
How often are autologous conditioned serum injections repeated?
Every 2 weeks for 3-4 treatments
What can be done with leftover IRAP serum?
Can be frozen for future use
Platelets are most commonly associated with _____ and _____. They are also a rich source of _____.
clotting, hemostasis, growth factors
What are growth factors?
Proteins that stimulate growth, proliferation, healing, or cellular differentiation in cells.