Menstrual blood cells display stem cell-like phenotypic markers and exert neuroprotection following transplantation in experimental stroke.
Cell therapy remains an experimental treatment for neurological disorders. A major obstacle in pursuing the clinical application of this therapy is finding the optimal cell type that will allow benefit 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 significantly 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 significantly 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 benefits afforded by transplanted menstrual blood-derived cells support their use as a stem cell source for cell therapy in stroke.
Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, University of South Florida College of Medicine, Tampa, Florida 33612, USA. cborlong@health.usf.edu
Cesar V
CV
Borlongan
Yuji
Y
Kaneko
Mina
M
Maki
Seong-Jin
SJ
Yu
Mohammed
M
Ali
Julie G
JG
Allickson
Cyndy D
CD
Sanberg
Nicole
N
Kuzmin-Nichols
Paul R
PR
Sanberg
D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001773:Blood Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D016923:Cell Death; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D008598:Menstruation / Q000097:blood*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism*; D033581:Stem Cell Transplantation / Q000379:methods; D020521:Stroke / Q000473:pathology / Q000601:surgery
D015415:Biomarkers; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; C486780:NANOG protein, human; C577484:NES protein, human; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D055746:Stage-Specific Embryonic Antigens