Mouse mesenchymal stem cells can support human hematopoiesis both in vitro and in vivo: the crucial role of neural cell adhesion molecule |
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Authors: | Xiaoli Wang Hiroko Hisha Tomomi Mizokami Wenhao Cui Yunze Cui Aiping Shi Changye Song Satoshi Okazaki Qing Li Wei Feng Junko Kato and Susumu Ikehara |
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Institution: | 1 First Dept. of Pathology;2 Regeneration Research Center for Intractable Diseases;3 Dept. of Transplantation for Regeneration Therapy, Kansai Medical Univ., Moriguchi City, Osaka, Japan and;4 Dept. of Breast Cancer, First Medical College, Jilin University, Changchun, Jilin, China |
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Abstract: | BackgroundWe previously established a mesenchymal stem cell line (FMS/PA6-P) from the bone marrow adherent cells of fetal mice. The cell line expresses a higher level of neural cell adhesion molecule and shows greater hematopoiesis-supporting capacity in mice than other murine stromal cell lines.Design and MethodsSince there is 94% homology between human and murine neural cell adhesion molecule, we examined whether FMS/PA6-P cells support human hematopoiesis and whether neural cell adhesion molecules expressed on FMS/PA6-P cells contribute greatly to the human hematopoiesis-supporting ability of the cell line.ResultsWhen lineage-negative cord blood mononuclear cells were co-cultured on the FMS/PA6-P cells, a significantly greater hematopoietic stem cell-enriched population (CD34+CD38? cells) was obtained than in the culture without the FMS/PA6-P cells. Moreover, when lineage-negative cord blood mononuclear cells were cultured on FMS/PA6-P cells and transplanted into SCID mice, a significantly larger proportion of human CD45+ cells and CD34+CD38? cells were detected in the bone marrow of SCID mice than in the bone marrow of SCID mice that had received lineage-negative cord blood mononuclear cells cultured without FMS/PA6-P cells. Furthermore, we found that direct cell-to-cell contact between the lineage-negative cord blood mononuclear cells and the FMS/PA6-P cells was essential for the maximum expansion of the mononuclear cells. The addition of anti-mouse neural cell adhesion molecule antibody to the culture significantly inhibited their contact and the proliferation of lineage-negative cord blood mononuclear cells.ConclusionsThese findings suggest that neural cell adhesion molecules expressed on FMS/PA6-P cells play a crucial role in the human hematopoiesis-supporting ability of the cell line. |
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Keywords: | neural cell adhesion molecule cord blood human hematopoiesis mesenchymal stem cells |
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