The present invention relates to pharmaceutical compositions comprising mesenchymal cells (MSCs) and additional agents for blocking co-stimulation of the immune system. The compositions may optionally further comprise a therapeutic cell, a therapeutic tissue, and/or a therapeutic organ implant. Additionally, the instant invention pertains to medical uses of such compositions in immune-mediated diseases and disorders, in essentially all inflammatory and/or autoimmune diseases and conditions, and also in transplantation-related conditions.