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 Heise T, DeVries JH, Urva S, Li J, Pratt EJ, Thomas MK, Mather KJ, Karanikas CA, Dunn J, Haupt A, Milicevic Z, Coskun T. Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes. Diabetes Care. 2023 May 1;46(5):998-1004. doi: 10.2337/dc22-1710. PMID: 36857477; PMCID: PMC10154650.

 White GE, Shu I, Rometo D, Arnold J, Korytkowski M, Luo J. Real-world weight-loss effectiveness of glucagon-like peptide-1 agonists among patients with type 2 diabetes: A retrospective cohort study. Obesity (Silver Spring). 2023 Feb;31(2):537-544. doi: 10.1002/oby.23622. Epub 2023 Jan 9. PMID: 36621904; PMCID: PMC9877131.

 Moll H, Frey E, Gerber P, Geidl B, Kaufmann M, Braun J, Beuschlein F, Puhan MA, Yebyo HG. GLP-1 receptor agonists for weight reduction in people living with obesity but without diabetes: a living benefit-harm modelling study. EClinicalMedicine. 2024 May 27;73:102661. doi: 10.1016/j.eclinm.2024.102661. PMID: 38846069; PMCID: PMC11154119. 

Regenerative Medicine

We believe that regenerative medicine has signaled the beginning of a shift in medicine to prevent the breakdown of our muscles, tendons and ligaments that make up our joints. Evidence shows that the body contains the ability to regenerate, heal and delay the aging of our joints through the use of mesenchymal stem cells, exosomes and products derived from wharton's jelly and umbillical cord blood.

What is the National Institutes of Health (NIH)?

 The National Institutes of Health (NIH) is a US agency that conducts medical research to improve health and save lives. It's part of the US Department of Health and Human Services 

 According to the NIH, Alpha-2-macroglobulin (A2M) is a naturally occurring protein that acts as a potent inhibitor of enzymes that break down cartilage, making it a treatment option for osteoarthritis (OA) by slowing down cartilage degeneration when injected directly into the affected joint due to its ability to suppress inflammatory processes involved in OA development; 

Functions: 

• Protease Inhibitor:

A2M is a potent inhibitor of a wide range of proteases, including enzymes involved in inflammation, coagulation, and cell growth. It traps and neutralizes proteases, preventing them from causing damage to tissues and cells. 

• ECM Regulation:

A2M helps maintain the integrity of the ECM by binding to proteases and preventing their degradation. It also interacts with other ECM components, such as collagen and elastin. 

• Immune Function:

A2M modulates the immune response by binding to cytokines and chemokines, reducing their inflammatory activity. It also facilitates the clearance of damaged cells and debris. 

• Transport and Clearance:

A2M acts as a carrier protein for various molecules, including growth factors, hormones, and enzymes. It transports them to their destination or facilitates their clearance from the body. 

Clinical Significance: 

• Disease Biomarker:

Low levels of A2M are associated with various diseases, including inflammatory conditions, cancer, and kidney disease. 

• Therapeutic Potential:

A2M has been investigated as a therapeutic agent for conditions characterized by excessive protease activity, such as arthritis and osteoporosis. 

Other Notes:

• A2M is produced mainly by the liver. 
• It is a glycoprotein, meaning it contains sugar molecules attached to its protein structure. 
• A2M is a member of the alpha-macroglobulin superfamily of proteins

 1. Orhurhu V, Schwartz R, Potts J, Peck J, Urits I, Orhurhu MS, Odonkor C, Viswanath O, Kaye A, Gill J. Role of Alpha-2-Microglobulin in the Treatment of Osteoarthritic Knee Pain: a Brief Review of the Literature. Curr Pain Headache Rep. 2019 Sep 9;23(11):82. doi: 10.1007/s11916-019-0822-9. Erratum in: Curr Pain Headache Rep. 2020 Feb 8;24(3):9. doi: 10.1007/s11916-020-0841-6. PMID: 31502073. 

2. Vandooren J, Itoh Y. Alpha-2-Macroglobulin in Inflammation, Immunity and Infections. Front Immunol. 2021 Dec 14;12:803244. doi: 10.3389/fimmu.2021.803244. PMID: 34970276; PMCID: PMC8712716. 

 Mesenchymal stem cells (MSCs) are multipotent cells that can be used to repair and regenerate damaged tissue. They are a key part of regenerative medicine and have been used to treat a variety of conditions. How MSCs work

• Proliferate: MSCs can replace dead cells in the body. 
• Secrete immunomodulatory molecules: MSCs create a regenerative environment that can reduce inflammation. 
• Differentiate: MSCs can differentiate into multiple cell lineages, including fibroblasts, chondrocytes, osteoblasts, and adipocytes. 

MSCs come from bone marrow (BMAC), adipose tissue (Lipoaspirate), umbilical cord, and dental pulp. 

MSC applications: neurological disorders, cardiac ischemia, diabetes, bone and cartilage diseases, autoimmune diseases, injury recovery, and degenerative conditions.

MSC safety: MSC therapy is generally safe and well-tolerated, but there are potential long-term side effects of therapy failure. 

MSC research: MSCs are a key part of regenerative medicine research, and many assays and tests have been developed to improve their safety and efficacy

 According to the NIH, Bone Marrow Aspirate Concentrate (BMAC) is a treatment option for osteoarthritis (OA), with studies showing it may help reduce pain and improve joint function by utilizing a patient's own bone marrow cells to promote tissue regeneration, although further research is needed to fully understand its efficacy and optimal application in OA treatment. BMAC is used to treat a variety of musculoskeletal conditions, including osteoarthritis, tendonitis, ligament tears, and bone fractures. It is a minimally invasive procedure that may be an alternative to surgery in some cases.

BMAC injections into 37 osteoarthritic knees with a 4-year follow up showing significant improvements in IKDC and WOMAC scores, and with a 95% success rate and significant improvement in walking distance. 

Pabinger, C., Lothaller, H. & Kobinia, G.S. Intra-articular injection of bone marrow aspirate concentrate (mesenchymal stem cells) in KL grade III and IV knee osteoarthritis: 4 year results of 37 knees. Sci Rep 14, 2665 (2024). https://doi.org/10.1038/s41598-024-51410-2 

 Lipoaspirate is a small amount of fat tissue that contains cells and fluid. It can be used in a variety of ways, including regenerative medicine, soft-tissue augmentation, and wound healing. 

How is lipoaspirate used?

• Regenerative medicine: Lipoaspirate can be used to treat knee osteoarthritis and other conditions. 

 Lipoaspirate (Adipose tissue) and potential for repair of cartilage defects...

Bosetti M, Borrone A, Follenzi A, Messaggio F, Tremolada C, Cannas M. Human Lipoaspirate as Autologous Injectable Active Scaffold for One-Step Repair of Cartilage Defects. Cell Transplant. 2016;25(6):1043-56. doi: 10.3727/096368915X689514. Epub 2015 Sep 21. PMID: 26395761.  

 Wharton's jelly is a gelatinous, connective tissue that surrounds the umbilical cord in humans. It is composed of various extracellular matrix components, including hyaluronic acid, collagen, and proteoglycans. 

Functions: 

• Protection: Wharton's jelly cushions and protects the umbilical cord from compression, torsion, and damage during fetal development. 
• Stem cell source: It contains mesenchymal stem cells, which have the potential to differentiate into various cell types, such as bone, cartilage, and fat
• Immune regulation: Wharton's jelly plays a role in regulating the immune system, potentially by releasing anti-inflammatory factors.