Mesenchymal Stromal Cells (MSCs) are being developed as a transfusional product to treat immune and inflammatory disorders. However, results of industry-sponsored randomized clinical trials that have utilized MSC-like cells have not met primary end points of efficacy for treatment of GvHD or inflammatory bowel disease. A better understanding of MSC mechanism of action would best inform future development strategies. MSC's immunosuppressive potential is markedly augmented by licensing by the proinflammatory cytokine, IFNγ. In the present review, we analyze the effect of MSC preparation methods on MSC's responsiveness to IFNγ and immune plasticity. The concept of pre-licensing with IFNγ on MSC's immunosuppressive, engraftment and therapeutic potential is also discussed.

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Administration of ex vivo expanded mesenchymal stromal cells (MSCs) represent a promising therapy for degenerative and inflammatory/autoimmune diseases. Indeed, mouse MSCs (mMSCs) and human MSCs (hMSCs) have shown very promising results in animal models for multiple diseases due to their trophic and immunomodulatory activities. However, human clinical trials have not reached the success found in preclinical models. The general consensus is that, for most applications, we should increase the “therapeutic potency” of MSCs before translation into clinic. This goal can be achieved by increasing/improving the migration, engraftment, differentiation and immunomodulatory activities of the MSCs. The present article summarizes some of the approaches that use gene-modified MSCs (GM-MSC) for the treatment of different disorders. We will also discuss our experience using GM-MSCs expressing vasoactive intestinal peptide (VIP) for the treatment of multiple sclerosis.

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Inflammatory Bowel Disease (IBD) is a highly debilitating and potentially fatal idiopathic disorder of the intestinal tract which is exceedingly prevalent in westernized society; however there is concern of an IBD epidemic in Asia due to increasing incidence rates. There is no cure for IBD with current treatments limited by their inefficacy, toxicity and adverse side-effects; thus necessitating the search for novel therapies. In the past decade mesenchymal stem cells (MSCs) have become attractive candidates for the cellular based therapy of IBD. MSCs are easily isolated and expanded from adult bone-marrow and adipose tissue; they possess unique therapeutic characteristics including the ability to home to sites of tissue damage and inflammation, facilitate tissue repair and modulate the immune system. The administration of MSCs in animal models of experimental colitis and clinical trials of fistulising and luminal Crohn's disease have yielded promising results, however an unequivocal therapeutic mechanism remains elusive. This review will explore the clinical application of MSCs in IBD and current evidence from experimental models of colitis elucidating their potential to ameliorate intestinal inflammation.

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Multipotent mesenchymal stromal cells (MSCs) have potential therapeutic uses owing to their ability to differentiate in situ into various cell types with immunosuppressive properties. Clinically, MSCs have been used to treat inflammatory diseases, such as steroid-resistant graft-versus-host disease. We previously reported a strategy to expand MSC cultures and to induce these cells to undergo myogenic differentiation, which is promising for the treatment of muscular diseases. Muscular dystrophy is an incurable genetic disease with early mortality and causes skeletal muscle weakness with chronic inflammation. Here, we focused on the beneficial properties of MSCs, namely, they can undergo mesoderm differentiation, have the ability to fuse with dystrophic muscles, and have anti-inflammatory activities. In this review, we highlight and discuss MSC-based therapeutic approaches for muscular dystrophy.

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We conducted a large scale epidemiological study in Japan and revealed a high mortality rate in RP patients with neurological involvement. Japanese RP patients developed encephalitis/meningitis (12 out of 239 cases, 5.0%), cerebral infarct/bleeding (5 cases, 2.1%) and cerebral vasculitis (4 cases, 1.7%). The mortality rate was 18%, in contrast to 8.1% of RP patients without neurological involvement. We suggested that neurological involvement appeared to be a major determinant of disease severity in patients with RP.

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