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Human bone marrow stromal cells simultaneously support B and T / NK lineage development from human haematopoietic progenitors: a principal role for flt3 ligand in lymphopoiesis
Author(s) -
Nakamori Yoshiki,
Liu Bing,
Ohishi Kohshi,
Suzuki Kei,
Ino Kazuko,
Matsumoto Takeshi,
Masuya Masahiro,
Nishikawa Hiroyoshi,
Shiku Hiroshi,
Hamada Hirofumi,
Katayama Naoyuki
Publication year - 2012
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2012.09109.x
Subject(s) - lymphopoiesis , stromal cell , haematopoiesis , bone marrow , biology , stem cell , immunology , progenitor cell , stem cell factor , microbiology and biotechnology , cancer research
Summary The regulation of human early lymphopoiesis remains unclear. B ‐ and T ‐lineage cells cannot develop simultaneously with conventional stromal cultures. Here we show that telomerized human bone marrow stromal cells supported simultaneous generation of CD 19 + CD 34 lo/− CD 10 + cy CD 79a + CD 20 +/− Vpre B − pro‐ B cells and CD 7 + CD 34 + CD 45 RA + CD 56 − cy CD 3 − early T /Natural Killer ( NK ) cell precursors from human haematopoietic progenitors, and the generation of both lymphoid precursors was promoted by flt3 ligand (flt3 L ). On the other hand, stem cell factor or thrombopoietin had little or no effect when used alone. However, both acted synergistically with flt3 L to augment the generation of both lymphoid precursors. Characteristics of these lymphoid precursors were evaluated by gene expression profiles, rearrangements of I g H genes, or replating assays. Similar findings were observed with primary human bone marrow stromal cells. Notably, these two lymphoid‐lineage precursors were generated without direct contact with stromal cells, indicating that early B and T / NK development can occur, at least in part, by stromal cell‐derived humoral factors. In serum‐free cultures, flt3 L elicited similar effects and appeared particularly important for B cell development. The findings of this study identified the potential of human bone marrow stromal cells to support human early B and T lymphopoiesis and a principal role for flt3 L during early lymphopoiesis.