Bone marrow engraftment but limited expansion of hematopoietic cells from multipotent germline stem cells derived from neonatal mouse testis

Momoko Yoshimoto, Toshio Heike, Hsi Chang, Mito Kanatsu-Shinohara, Shiro Baba, Joseph T. Varnau, Takashi Shinohara, Mervin C. Yoder, Tatsutoshi Nakahata

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Objective: Multipotent germline stem (mGS) cells derived from neonatal mouse testis, similar to embryonic stem (ES) cells, differentiate into various types of somatic cells in vitro and produce teratomas after inoculation into mice. In the present work, we examined mGS cells for hematopoietic progenitor potential in vitro and in vivo. Materials and Methods: mGS cells were differentiated on OP9 stromal cells and induced into Flk1+ cells. Flk1+ cells were sorted and replated on OP9 stromal cells with various cytokines and emerging hematopoietic cells were analyzed for lineage marker expression by fluorescein-activated cell sorting, progenitor activity by colony assay, and stem cell transplantation assay. Results: mGS cells, like ES cells, produce hematopoietic progenitors, including both primitive and definitive erythromyeloid, megakaryocyte, and B- and T-cell lineages via Flk1+ progenitors. When transplanted into the bone marrow (BM) of nonobese diabetic/severe combined immunodeficient (NOD/SCID) γcnull mice directly, mGS-derived green fluorescent protein (GFP)-positive cells were detected 4 months later in the BM and spleen. GFP+ donor cells were also identified in the Hoechst33342 side population, a feature of hematopoietic stem cells. However, these mGS-derived hematopoietic cells did not proliferate in vivo, even after exposure to hematopoietic stressors, such as 5-fluorouracil (5FU) injection or serial transplantation. Conclusion: mGS cells produced multipotent hematopoietic progenitor cells with myeloid and lymphoid lineage potential in vitro and localized in the BM after intra-BM injection but, like ES cells, failed to expand or show stem cell repopulating ability in vivo.

Original languageEnglish
Pages (from-to)1400-1410
Number of pages11
JournalExperimental Hematology
Volume37
Issue number12
DOIs
Publication statusPublished - Dec 2009
Externally publishedYes

Fingerprint

Multipotent Stem Cells
Testis
Bone Marrow
Embryonic Stem Cells
Hematopoietic Stem Cells
Stromal Cells
Green Fluorescent Proteins
Stem Cells
Colony-Forming Units Assay
Injections
Megakaryocytes
SCID Mice
Teratoma
Stem Cell Transplantation
Cell Lineage
Fluorescein
Fluorouracil
Spleen
Transplantation
Cytokines

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Hematology

Cite this

Bone marrow engraftment but limited expansion of hematopoietic cells from multipotent germline stem cells derived from neonatal mouse testis. / Yoshimoto, Momoko; Heike, Toshio; Chang, Hsi; Kanatsu-Shinohara, Mito; Baba, Shiro; Varnau, Joseph T.; Shinohara, Takashi; Yoder, Mervin C.; Nakahata, Tatsutoshi.

In: Experimental Hematology, Vol. 37, No. 12, 12.2009, p. 1400-1410.

Research output: Contribution to journalArticle

Yoshimoto, M, Heike, T, Chang, H, Kanatsu-Shinohara, M, Baba, S, Varnau, JT, Shinohara, T, Yoder, MC & Nakahata, T 2009, 'Bone marrow engraftment but limited expansion of hematopoietic cells from multipotent germline stem cells derived from neonatal mouse testis', Experimental Hematology, vol. 37, no. 12, pp. 1400-1410. https://doi.org/10.1016/j.exphem.2009.09.006
Yoshimoto, Momoko ; Heike, Toshio ; Chang, Hsi ; Kanatsu-Shinohara, Mito ; Baba, Shiro ; Varnau, Joseph T. ; Shinohara, Takashi ; Yoder, Mervin C. ; Nakahata, Tatsutoshi. / Bone marrow engraftment but limited expansion of hematopoietic cells from multipotent germline stem cells derived from neonatal mouse testis. In: Experimental Hematology. 2009 ; Vol. 37, No. 12. pp. 1400-1410.
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AU - Baba, Shiro

AU - Varnau, Joseph T.

AU - Shinohara, Takashi

AU - Yoder, Mervin C.

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