Katarina Le Blanc group
Experimental and clinical studies of the immunological properties of fetal and adult mesenchymal stem cells (MSC), intracellular mechanisms for differentiation and the use of MSC cell therapy.
Bone marrow derived MSCs suppress immune responses and are anti-inflammatory, although their mode of immunosuppressive function remains largely unconfirmed. In tissue, MSCs reside in niches wrapped around endothelial cells lining capillary and venule walls. Their function is not constitutive or fixed, but the result of micro-environmental cross-talk. With reciprocal communication, MSCs and immune cells regulate each other’s immunomodulatory and antimicrobial properties, self-renewal and differentiation during tissue repair.
We were the first to report that adoptive transfer of MSCs ameliorates treatment-resistant acute graft-versus-host disease (GvHD), a potential life-threatening condition after allogeneic hematopoietic stem cell transplantation (aHSCT). Treatment with MSCs is now approved, or near regulatory approval, in countries, including Japan, Canada and the US. In contrast, MSC treatment of chronic GvHD has been less studied and is currently one of our main research areas. We believe the MSC can shift the patient’s immune system towards a more tolerogenic profile and thereby reducing the symptoms and increasing the quality of life.
In addition to classical GvHD symptoms, chronic fatigue and cognitive dysfunction represent factors of significant morbidity for aHSCT patients. We have recently reported the first battery of neuropsychological tests with the ability to qualitatively and quantitatively evaluate both persistent fatigue and cognitive function after aHSCT. Ongoing clinical studies will further help us to characterize this condition and find possible therapies.
The clinical-grade MSC-product that we have developed since 2003 have been used in several clinical trials for indications such as GvHD, type 1 diabetes, regeneration of vocal fold scarring and multiple sclerosis. The last years we have implemented full GMP in production of the cell products, a requirement since the MSC was classified as ATMP (Advanced Therapeutic Medicinal Products). We are now working on initiating new clinical trials.
Research group leader
The Katarina Le Blanc Research Group and Laboratories are located at the Karolinska Institutet, ANA Futura, level 8, Alfred Nobels Allé 8, Flemingsberg.
Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells.
Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, et al
Lancet 2004 May;363(9419):1439-41
Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al
Cytotherapy 2006 ;8(4):315-7
Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease.
Ringdén O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lönnies H, et al
Transplantation 2006 May;81(10):1390-7
Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study.
Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, et al
Lancet 2008 May;371(9624):1579-86
Multipotent mesenchymal stromal cells and the innate immune system.
Le Blanc K, Mougiakakos D
Nat. Rev. Immunol. 2012 Apr;12(5):383-96