Mesenchymal Stem Cell Studies
Virtually any disease that results from malfunctioning, damaged or failing tissues may be potentially cured through regenerative medicine therapies. US Department of Health and Human Services
There are numerous clinical studies looking at the role of MSCs in emerging therapies. The National Institutes of Health public clinical trials database (www.clinicaltrials.gov) showed 123 clinical trials using MSCs for a wide range of therapeutic applications as of February 2011 (Figure 1). By January 2012 this number was 210 trials. The majority of these are in Phase I (safety studies), Phase II (proof of concept for efficacy) or a mixture of Phase I/II studies*. They include bone and cartilage repair (cell types into which MSCs readily differentiate), immune therapies for conditions such as graft versus host disease and autoimmune conditions (that use the MSCs immunosuppressive properties).
*Trounson et al. Clinical trials for stem cell therapies. BMC Medicine 2011,9:52
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterised by extensive mononuclear cell infiltration and demyelination. MS is generally considered to be an autoimmune disease based on local inflammation and response to immune modulation or immunosuppression. The best characterised animal model of MS is experimental allergic encephalomyelitis (EAE) induced by immunization of susceptible host animals with specific myelin proteins. Recent studies demonstrated that human bone marrow-derived MSCs promote functional recovery in both chronic and relapsing models of mouse EAE. Specifically the cells appear to migrate to demyelinating lesions of the inflamed CNS where they regulate the balance of T lymphocytes and modify the cytokines released during EAE. This data suggests that MSCs may represent a viable option for therapeutic approaches to treating demyelinating diseases such as MS and other neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease.
There are now a number of clinical trials looking at autologous mesenchymal stem cell transplantation in MS (www.clinicaltrials.gov).
Osteoarthritis is a degenerative disease resulting in increasing pain, impairment to movement and ultimately disability. For early stage osteoarthritis, treatment is largely limited to addressing the symptoms of inflammation with non-steroidal anti-inflammatory drugs. These drugs do not stop the progression of the disease or regenerate the damaged cartilage and researchers continue to explore alternative cartilage repair strategies. The availability of large quantities of MSCs and their potential for chondrogenic differentiation after prolonged in vitro expansion have made MSCs a promising progenitor cell source for cartilage tissue engineering. Clinical trials are now underway looking at the efficacy of using MSCs to regenerate defective cartilage tissue and improve function (http://www.clinicaltrials.gov/ NCT01300598)
Type 1 Diabetes
Type 1 diabetes is characterised by the autoimmune destruction of the pancreatic β cells. Patients require multiple daily insulin injections throughout their lives as well as close monitoring of their diet and blood sugar levels to prevent complications. MSCs possess specific immunomodulatory properties that researchers hope will help control the autoimmune response to β cells in patients with T1D and clinical trials are now underway looking at efficacy of MSC infusion in T1D (www.clinicaltrials.gov/ NCT01219465).
Failure of bone repair is a challenging problem in the management of fractures. MSCs hold promise for healing bones because of their capacity to differentiate into osteoblasts and there are now a number of clinical studies which have shown that implantation of MSCs is an effective, safe and durable method for aiding the repair and regeneration of bone*.
Griffin et al. Exploring the application of mesenchymal stem cells in bone repair and regeneration. J Bone Joint Surg Br 2011, 93(4):427-434