Human Umbilical Cord
Mesenchymal Stem Cells
Umbilical Cord Tissue-derived Mesenchymal Stem Cells for 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]. On the one hand, MSC produce soluble factors that a¡¡re antioxidant , antifibrotic , and stimulate endogenous chondrogenic progenitors , on the other hand MSC directly can differentiate into cartilage tissue .
The proposed study will involve intra-articular injection of umbilical cord tissue mesenchymal stem cells (UC-MSC) into joints of 20 patients with grade 2-4 radiographic OA severity and intravenously in 20 patients with grade 2-4 radiographic OA severity. The primary endpoint will be safety and feasibility 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 3 and 12 months after treatment.
This, study will provide support for double-blind placebo controlled investigations. The potential of using UC-MSC 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.
- Kemp, K., et al., Mesenchymal stem cell-secreted superoxide dismutase promotes cerebellar neuronal survival. J Neurochem, 2010. 114(6): p. 1569-80.>/li>
- 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.
- Gupta, P.K., et al., Mesenchymal stem cells for cartilage repair in osteoarthritis. Stem Cell Res Ther, 2012. 3(4): p. 25.