Mesenchymal Trophic Factor
Safety and Feasibility Study of Mesenchymal Trophic Factor (MTF) for Treatment of Osteoarthritis
Osteoarthritis (OA) is a chronic degenerative condition of the articular cartilage, which is the most common cause of disability in patients over age 65. Treatment options are limited towards alleviating symptomology.
Mesenchymal stem cells (MSC) are effective at treating osteoarthritis (OA) in animal models and clinical trials [1-6]. Mechanisms of therapeutic activity appear to be associated with regenerative and anti-inflammatory factors produced by MSC [7, 8]. Mesenchymal trophic factor (MTF) is a preparation of cytokines and growth factors that are collected from the conditioned media of MSC grown in animal-free media. MTF allows for patients to be provided various benefits of MSC therapy without the need to administer cells. This allows for larger accessibility of treatment, as well as potential economic benefit. MTF has been demonstrated to possess anti-inflammatory [9, 10], antioxidant , antifibrotic , and regenerative properties  in vitro and in vivo.
The proposed study will involve two arms of 20 patients per arm suffering from grade 2-4 radiographic OA severity. The first arm will receive intra-articular injection of 3 ml of MTF into the knee joint under fluoroscopy. The second arm will receive 12 subcutaneous injections, once per week, of MTF. For both arms, the primary endpoint will be safe and feasible as assessed by lack of treatment associated adverse events. The secondary endpoint will be improvements in joint function as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Patients will be examined at baseline and at 3 and 12 months after treatment.
This, study will provide support for double-blind placebo controlled investigations. The potential of using MTF for this debilitating condition will open the door for future investigations in other inflammatory conditions if results demonstrate safety and feasibility of this approach.
- Age >18 years and ability to understand the planned treatment.
- Subjects 18 years of age or older with idiopathic or secondary osteoarthritis of the knee with grade 2, 3, or 4 radiographic severity, as defined by the modified Kellgren–Lawrence classification
- Pregnant women or cognitively impaired adults.
- Presence of large meniscal tears (“bucket handle” tears), as detected by clinical examination or by magnetic resonance imaging.
- Inflammatory or post infectious arthritis.
- More than 5 degrees of varus or valgus deformity.
- Kellgren Lawrence grade 4 osteoarthritis in two compartments (the medial or lateral compartments of the tibiofemoral joint or the patellofemoral compartment) in persons over 60 years of age.
- Intra-articular corticosteroid injection within the previous 3 months.
- A major neurologic deficit.
- Serious medical illness with a life expectancy of less than 1 year.
- Prior admission for substance abuse
- Body Mass Index (BMI) of 40 kg/m2 or greater
- Patient receiving experimental medication or participating in another clinical study within 30 days of signing the informed consent
- In the opinion of the investigator or the sponsor the patient is unsuitable for cellular therapy
- Black, L.L., et al., Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial. Vet Ther, 2007. 8(4): p. 272-84.
- Grigolo, B., et al., Osteoarthritis treated with mesenchymal stem cells on hyaluronan-based scaffold in rabbit. Tissue Eng Part C Methods, 2009. 15(4): p. 647-58.
- Emadedin, M., et al., Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med, 2012. 15(7): p. 422-8.
- Koh, Y.G. and Y.J. Choi, Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee, 2012.
- Pak, J., Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series. J Med Case Rep, 2011. 5: p. 296.
- Davatchi, F., et al., Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis, 2011. 14(2): p. 211-5.
- van Buul, G.M., et al., Mesenchymal stem cells secrete factors that inhibit inflammatory processes in short-term osteoarthritic synovium and cartilage explant culture. Osteoarthritis Cartilage, 2012. 20(10): p. 1186-96.
- Lo, W.C., et al., Preferential therapy for osteoarthritis by cord blood MSCs through regulation of chondrogenic cytokines. Biomaterials, 2013. 34(20): p. 4739-48.
- Tsyb, A.F., et al., In vitro inhibitory effect of mesenchymal stem cells on zymosan-induced production of reactive oxygen species. Bull Exp Biol Med, 2008. 146(1): p. 158-64.
- Tu, Z., et al., Mesenchymal stem cells inhibit complement activation by secreting factor H. Stem Cells Dev, 2010. 19(11): p. 1803-9.
- Kemp, K., et al., Mesenchymal stem cell-secreted superoxide dismutase promotes cerebellar neuronal survival. J Neurochem, 2010. 114(6): p. 1569-80.
- Ortiz, L.A., et al., Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci U S A, 2007. 104(26): p. 11002-7.
- Osugi, M., et al., Conditioned media from mesenchymal stem cells enhanced bone regeneration in rat calvarial bone defects. Tissue Eng Part A, 2012. 18(13-14): p. 1479-89.