Published online 31 March 2009
Haematologica, Vol 94, Issue 5, 618-628 doi:10.3324/haematol.2008.004705
Copyright © 2009 by Ferrata Storti Foundation
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Hematopoietic Stem Cells

Preferential expansion of human umbilical cord blood-derived CD34-positive cells on major histocompatibility complex-matched amnion-derived mesenchymal stem cells

Tomomi Mizokami1,4, Hiroko Hisha1,2,3, Satoshi Okazaki1, Takashi Takaki1, Xiao-Li Wang1, Chang-Ye Song1, Qing Li1, Junko Kato1, Naoki Hosaka1,2, Muneo Inaba1,2, Hideharu Kanzaki4, Susumu Ikehara1,2,3

1 First Dept. of Pathology
2 Regeneration Research Center for Intractable Diseases
3 Dept. of Transplantation for Regeneration Therapy
4 Dept. of Obstetrics and Gynecology, Kansai Medical University, Moriguchi City, Osaka, Japan

Correspondence: Susumu Ikehara, First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan. E-mail:ikehara{at}takii.kmu.ac.jp

Background: We previously found in a murine hematopoietic system that hematopoietic stem cells show high differentiation and proliferation capacity on bone marrow-derived mesenchymal stem cells/stromal cells (microenvironment) with "self" major histocompatibility complex (MHC).

Design and Methods: We examined whether amnion-derived adherent cells have the characteristics of mesenchymal stem cells, and whether these adherent cells can support the proliferation of umbilical cord blood-derived lineage-negative and CD34-positive cells (Lin–CD34+ cells) obtained from the same fetus to a greater extent than those derived from other fetuses.

Results: Culture-expanded amnion-derived adherent cells expressed mesenchymal stem cell markers and HLA-ABC molecules and could differentiate into osteoblasts, adipocytes and chondrocyte-like cells, indicating that the cells have the characteristics of mesenchymal stem cells. The Lin–CD34+ cells purified from the frozen umbilical cord blood were strongly positive for HLA-ABC, and contained a large number of hematopoietic stem cells. When the Lin–CD34+ cells were cultured on the autologous (MHC-matched) or MHC-mismatched amnion-derived adherent cells in short-term assays (hematopoietic stem cell-proliferation) and long-term culture-initiating cell assays, greater expansion of the Lin–CD34+ cells was observed in the MHC-matched combination than in MHC-mismatched combinations. The concentration of granulocyte-macrophage colony-stimulating factor in the culture supernatants of the long-term culture-initiating cell assays was significantly higher in the MHC-matched combination than in MHC-mismatched combinations.

Conclusions: It is likely that a MHC restriction exists between hematopoietic stem cells and mesenchymal stem cells/stromal cells in the human hematopoietic system and that granulocute-macropage colony-stimulating factor contributes to some extent to the preferential hematopoiesis-supporting ability of the MHC-matched amnion-derived adherent cells.

Key words: mesenchymal stem cells, CD34-positive cells, umbilical cord blood, amnion, major histocompatibility complex.