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This Article Free via Open Access: OA OA Full Text Full Text (PDF) Supplemental Data OA All Versions of this Article: 2008-0379v1 26/10/2516    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kim, J. Articles by Rafii, S. Search for Related Content PubMed PubMed Citation Articles by Kim, J. Articles by Rafii, S.

THE STEM CELL NICHE

CD34+ Testicular Stromal Cells Support Long-Term Expansion of Embryonic and Adult Stem and Progenitor Cells

^aHoward Hughes Medical Institute, Ansary Center for Stem Cell Therapeutics, and Department of Genetic Medicine,
^cCenter for Reproductive Medicine and Infertility, Weill Cornell Medical College, New York, New York, USA;
^bDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

Key Words. CD34 • Spermatogonia • Germ cells • Stem cells • Adult stem cells • Embryonic stem cells • Multipotent stem cells • Pluripotent stem cells • OCT4

Correspondence: Correspondence: Shahin Rafii, M.D.,Howard Hughes Medical Institute, Weill Medical College of Cornell University, 1300 York Avenue, A-863, New York, New York 10065, USA. Telephone: 212-746-2070; Fax: 212-746-8481; e-mail: srafii{at}med.cornell.edu; or Marco Seandel, M.D., Ph.D.,Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 8, New York, New York 10065, USA. Telephone: 212-746-2017; Fax: 212-746-8481; e-mail: seandelm{at}mskcc.org

Received on April 24, 2008; accepted for publication on July 14, 2008.

First published online in STEM CELLS EXPRESS  July 31, 2008.

Stem cells reside in specialized microenvironments created by supporting stromal cells that orchestrate self-renewal and lineage-specific differentiation. However, the precise identity of the cellular and molecular pathways that support self-renewal of stem cells is not known. For example, long-term culture of prototypical stem cells, such as adult spermatogonial stem and progenitor cells (SPCs), in vitro has been impeded by the lack of an optimal stromal cell line that initiates and sustains proliferation of these cells. Indeed, current methods, including the use of mouse embryonic fibroblasts (MEFs), have not been efficient and have generally led to inconsistent results. Here, we report the establishment of a novel CD34-positive cell line, referred to as JK1, derived from mouse testicular stromal cells that not only facilitated long-term SPC culture but also allowed faithful generation of SPCs and multipotent stem cells. SPCs generated on JK1 maintained key features of germ line stem cells, including expression of PLZF, DAZL, and GCNA. Furthermore, these feeders also promoted the long-term cultivation of other types of primitive cells including multipotent adult spermatogonial-derived stem cells, pluripotent murine embryonic stem cells, and embryonic germ cells derived from primordial germ cells. Stem cells could be passaged serially and still maintained expression of characteristic markers such as OCT4 and NANOG in vitro, as well as the ability to generate all three germ layers in vivo. These results indicate that the JK1 cell line is capable of promoting long-term culture of primitive cells. As such, this cell line allows for identification of stromal-derived factors that support long-term proliferation of various types of stem cells and constitutes a convenient alternative to other types of feeder layers.

Disclosure of potential conflicts of interest is found at the end of this article.