Skin cell therapy for the long term treatment of alopecia areata
The purpose of this study is to investigate the potential for cells that produce the enzyme, Indoleamine 2,3-dioxygenase (IDO), to inhibit inflammation and hair loss in the C3H/HeJ alopecia areata mouse model.
Alopecia areata (AA), defined as a non-scarring autoimmune hair loss disease, has a serious impact on the quality of life for AA patients worldwide. It is well established that infiltrated immune cells, known as CD4+ and CDS+ lymphocytes, target the hair follicles of AA patients. Various therapeutic regimens are currently used for the treatment of AA; however, none of them can prevent or cure the disease. We found that the use of Indoleamine 2,3-dioxygenase (IDO) producing skin cell therapy prevents the progression of type I diabetes, another autoimmune disease, by suppressing both CD4+ and CDS+ cells in diabetic mice. This novel observation suggests that our treatment strategy could also prevent the progression of AA. Our preliminary results with the C3H/HeJ mouse model for AA revealed that none of the IDO skin cell treated mice (n= 3) developed AA while 80% of control animals developed extensive AA within 8-16 weeks after transplantation of AA affected skin. Here we hypothesize that IDO expressing fibroblast cell therapy can prevent the progression of AA by suppressing the CD4+ and CDS+ cells attacking hair follicles. To address this hypothesis, we will evaluate: 1) The efficacy of IDO expressing fibroblasts in preventing AA development in more C3H/HeJ mice, 2) The presence and type of infiltrated immune cells, such as CD4+ and CDS+ cells not only in hair follicles, but also in lymph nodes using different methods, and 3) The immune cell signaling proteins, known as cytokines, both in and around the hair follicles and in blood samples. In conclusion, we strongly believe that, if proven true, our novel cell therapy approach would overcome the AA autoimmunity and prevent the progression of AA. Potentially this may be a long lasting, possibly permanent treatment for patients who suffer from this devastating skin disorder.
Results show the injection of IDO-producing skin cell therapy suppresses the autoimmune response, preventing the progression of alopecia areata. Eighty percent of control mice acquired alopecia areata while none of the IDO cell therapy group was affected. These results were used to apply for additional funding from the Canadian Institute of Health Research to conduct more mechanistic studies.
Jalili RB, Kilani RT, Li Y, Khosravi-Maharlooie M, Nabai L, Wang EHC, McElwee KJ, Ghahary A. Fibroblast cell-based therapy prevents induction of alopecia areata in an experimental model. Cell Transplant. 2018 Jun;27(6):994-1004. doi: 10.1177/0963689718773311.