Methods and Compositions for Producing Germ Cells from Bone Marrow Derived Germline Stem Cells

Abstract

The present invention provides bone marrow derived germline stem cells and their progenitors, methods of isolation thereof, and methods of use thereof.

1 - 69 . (canceled) 
     
     
         70 . A method of treating infertility in a mammalian female subject in need thereof, comprising obtaining a bone marrow sample having detectable levels of Dazl and Stella markers from the mammalian female subject, and administering the bone marrow sample into an ovary of the mammalian female subject, thereby treating infertility in a mammalian female subject. 
     
     
         71 . The method of  claim 70 , wherein the female subject is in a stage of either peri- or post-menopause. 
     
     
         72 . The method of  claim 70 , further comprising administering to the female subject an inhibitor of histone deacetylase (HDAC) activity. 
     
     
         73 . The method of  claim 71 , wherein the inhibitor of HDAC activity is trichostatin A. 
     
     
         74 . The method of  claim 70 , wherein oocyte production in the female subject is increased. 
     
     
         75 . The method of  claim 70 , wherein the female subject is a menopausal female subject. 
     
     
         76 . The method of  claim 70 , wherein the menopause is caused by aging or pathological processes. 
     
     
         77 . The method of  claim 76 , wherein the symptoms and consequences of menopause are ameliorated. 
     
     
         78 . The method of  claim 70 , wherein the female subject has polycystic ovary disease, a genetic disorder, an immune disorder or a metabolic disorder. 
     
     
         79 . The method of  claim 72 , further comprising administering to the female subject a retinoic acid. 
     
     
         80 . The method of  claim 70 , wherein the female subject is human. 
     
     
         81 . The method of  claim 70 , wherein a pharmaceutical composition comprising the bone marrow sample and a pharmaceutically acceptable carrier is administered to the female subject. 
     
     
         82 . The method of  claim 70 , further comprising administering to the female subject a transforming growth factor. 
     
     
         83 . The method of  claim 70 , wherein the bone marrow sample comprises bone marrow derived female germline stem cells. 
     
     
         84 . The method of  claim 70 , wherein the bone marrow sample comprises bone marrow derived female germline stem cell progenitors. 
     
     
         85 . The method of  claim 83 , wherein the female germline stem cells are mitotically competent and express Oct 4, Vasa, Stella and Fragilis. 
     
     
         86 . The method of  claim 85 , wherein the female germline stem cells further express Nobox, c-Kit and Sca-1. 
     
     
         87 . The method of  claim 83 , wherein the female germline stem cells do not express growth/differentiation factor-9 (GDF-9), zona pellucida proteins, histone deacetylase-6 (HDAC6) and synaptonemal complex protein-3 (SCP3). 
     
     
         88 . The method of  claim 84 , wherein the female germline stem progenitor cells are mitotically competent and express Oct 4, Vasa, Stella and Fragilis. 
     
     
         89 . The method of  claim 88 , wherein the female germline stem progenitor cells further express Nobox, c-Kit and Sca-1. 
     
     
         90 . The method of  claim 84 , wherein the female germline stem progenitor cells do not express growth/differentiation factor-9 (GDF-9), zona pellucida proteins, histone deacetylase-6 (HDAC6) and synaptonemal complex protein-3 (SCP3).