Menstrual Blood Cells Display Stem Cell–Like Phenotypic Markers and Exert Neuroprotection Following Transplantation in Experimental Stroke

Abstract

Cell therapy remains an experimental treatment for neurological disorders. A major obstacle in pursuing the clinical application of this therapy is fi nding the optimal cell type that will allow benefi t to a large patient population with minimal complications. A cell type that is a complete match of the transplant recipient appears as an optimal scenario. Here, we report that menstrual blood may be an important source of autologous stem cells. Immunocytochemical assays of cultured menstrual blood reveal that they express embryonic-like stem cell phenotypic markers (Oct4, SSEA, Nanog), and when grown in appropriate conditioned media, express neuronal phenotypic markers (Nestin, MAP2). In order to test the therapeutic potential of these cells, we used the in vitro stroke model of oxygen glucose deprivation (OGD) and found that OGD-exposed primary rat neurons that were co-cultured with menstrual blood-derived stem cells or exposed to the media collected from cultured menstrual blood exhibited signifi cantly reduced cell death. Trophic factors, such as VEGF, BDNF, and NT-3, were up-regulated in the media of OGD-exposed cultured menstrual blood-derived stem cells. Transplantation of menstrual blood-derived stem cells, either intracerebrally or intravenously and without immunosuppression, after experimentally induced ischemic stroke in adult rats also signifi cantly reduced behavioral and histological impairments compared to vehicle-infused rats. Menstrual blood-derived cells exemplify a source of "individually tailored" donor cells that completely match the transplant recipient, at least in women. The present neurostructural and behavioral benefi ts afforded by transplanted menstrual blood-derived cells support their use as a stem cell source for cell therapy in stroke.

Menstrual blood-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells

“…Endometrial tissue is a prolific source of stem cells that reoccur monthly . Many studies have demonstrated that endometrial stem cells can be harvested from menstrual blood by a non-invasive method Borlongan et al, 2010;Phuc et al, 2011;Allickson and Xiang, 2012). Consistent with previous reports, the MenSCs used in our study expressed classic MSC markers (CD29, CD73, CD90, and CD105) but did not express hematopoietic stem cell markers (CD34 and CD45) and immune activation markers (HLA-DR) Borlongan et al, 2010;Phuc et al, 2011;Allickson and Xiang, 2012).…”

“…Many studies have demonstrated that endometrial stem cells can be harvested from menstrual blood by a non-invasive method Borlongan et al, 2010;Phuc et al, 2011;Allickson and Xiang, 2012). Consistent with previous reports, the MenSCs used in our study expressed classic MSC markers (CD29, CD73, CD90, and CD105) but did not express hematopoietic stem cell markers (CD34 and CD45) and immune activation markers (HLA-DR) Borlongan et al, 2010;Phuc et al, 2011;Allickson and Xiang, 2012). As mentioned by , the MenSCs are also positive for both Oct-4 and SSEA-4 markers expressed by human embryonic stem cells, which may explain their rapid expansion and multi-potent capability in this study .…”

“…MenSCs transferred dystrophin into dystrophied myocytes through cell fusion and transdifferentiation in vitro and in vivo Toyoda et al, 2007). Furthermore, stem cells isolated from endometrium have been proven to be an excellent cell source for treating experimental disease models, such as critical limb ischemia, stroke, type I diabetes mellitus, Parkinson's disease, and other neurodegenerative disorders (Murphy et al, 2008;Borlongan et al, 2010;Li H.Y. et al, 2010;Sanberg et al, 2011;Santamaria et al, 2011).…”

Menstrual Stem cells

“…Burns, various skin diseases [12]. Heart disease, osteoarthritis and rheumatoid arthritis, acute lung injury and for the treatment of type 1 diabetes.…”

Obtenção de células-tronco provenientes do fluido menstrual: transporte, isolamento, caracterização, expansão e criopreservação

“…As células obtidas de fluido menstrual foram testadas com sucesso em animais na regeneração de membros inferiores 43 e em acidente vascular cerebral 44 . Hida et al 47 demonstraram que transplante de células-tronco do sangue menstrual em miocárdio de ratos pós-infarto possibilitou a regeneração do miocárdio com restauro da função cardíaca.…”