Tuesday March 18 2008
CEA
Definition of the tolerability properties of mesenchymal stem cells*
Stem Cells 2008, 26:212-222.
CEA
Challenges: Anti-graft-rejection cell therapy in bone marrow and solid organ transplantation
Which molecules are involved in the tolerance possessed by mesenchymal stem cells? What could be the therapeutic applications for these cells? These are the kind of questions being asked by the I²BM's SRHI unit working with the Besançon branch of the National Blood Service. This research has important implications for defining new therapeutic strategies to cut down the incidence of graft rejection following transplants of bone marrow or solid organs like the kidney.
Mesenchymal stem cells cultured from adult bone marrow are multipotent, meaning they can differentiate into a variety of cell types to form bone, cartilage, adipose tissue, tendons, muscle, and neurons. These cells are already very strong candidates for important applications in regenerative medicine. Furthermore, mesenchymal stem cells possess immunosuppressive properties that could well prove extremely useful for preventing rejection in solid and liquid tissue transplants, particularly graft-versus-host reaction following bone marrow transplants.
It is in this setting that the SRHI recently demonstrated1 that adult mesenchymal stem cells (MSCs) from bone marrow secrete the soluble form of HLA-G. HLA-G molecules fulfil a crucial function, since they are directly involved in the immune-tolerance properties of MSCs. During a series of experiments neutralising the HLA-G molecule's function, the researchers observed that the immune cells involved in graft rejection were no longer inhibited by the MSCs. This means that HLA-G plays a pivotal role in the immunosuppressive action of MSCs.
This is a fundamental, ground-breaking discovery, since it defines a novel mechanism by which MSCs can induce a microenvironment of immune tolerance. These characteristics will only further spur the intense investigations being led in regenerative medicine as well as in transplantation. Adult bone marrow-cultured MSCs could potentially be co-grafted as an immunosuppressive treatment following haematopoietic stem cell or solid organ grafts. The clinical repercussions are significant. MSCs could for example be employed to develop new therapeutic anti-rejection strategies.
*mesenchymal: mesenchymal stem cells are non-haematopoietic stem cells (not progenitors of blood cells) found in bone marrow around the vascular network. MSCs in the bone marrow act as embryonic connective tissue (or mesenchyme) for haematopoietic stem cells.
1Reference: Selmani Z., NajiA., ZidiI., FavierB., GaiffeE., ObertL., BorgC., SaasP., TiberghienP., Rouas-FreissN., CarosellaE.D., Deschaseaux F. HLA-G5 secretion by Human Mesenchymal Stem Cells Is Required to Suppress T-lymphocyte and NK Function and to Induce CD4+CD25highFOXP3+ Regulatory T Cells. Stem Cells 2008, 26:212-222.
Contact: Nathalie Rouas-Freiss / Nathalie.Rouas-Freiss@ cea.fr