Myofibroblastic stromal cells isolated from human bone marrow induce the proliferation of both early myeloid and B-lymphoid cells.
Normal human bone marrow stromal cells (BMSC) were isolated from Dexter-type long-term cultures according to their capacity to adhere to plastic and to their lack of hematopoietic antigens. The BMSC displayed a homogeneous appearance and a myofibroblastic phenotype in culture. The stromal cells (SC) were shown to support the proliferation of purified CD34+ hematopoietic progenitors and permitted us to maintain myeloid cells for several weeks in culture. In addition, the BMSC induced the proliferation of purified CD10+ s mu- fetal BM B-cell precursors (BCP). The capacity of the BMSC to induce the proliferation of early myeloid cells was shared by several other human fibroblastic-like cell types. In contrast, the BMSC were far superior to other adherent cells for induction of BCP proliferation. This capacity was largely mediated by endogenously produced interleukin-7 (IL-7), because it could be inhibited by anti-IL-7 antibody. In line with this finding, addition of IL-7 considerably enhanced BCP proliferation in cocultures with skin fibroblasts or synoviocytes. Thus, production of IL-7 appears to be a critical parameter that determines the ability of fibroblastic-like cells to induce BCP proliferation. Taken together, our data show that normal human myofibroblastic BMSC induce the proliferation of both early myeloid and B-lymphoid cells in the absence of accessory hematopoietic cells. The present system should constitute a model to study interactions between native human BM myofibroblastic stroma and various hematopoietic cell subsets.
Moreau
I
I
Schering-Plough Laboratory for Immunological Research, Dardilly, France.
Duvert
V
V
Caux
C
C
Galmiche
M C
MC
Charbord
P
P
Banchereau
J
J
Saeland
S
S
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells; D015815:Cell Adhesion Molecules / Q000502:physiology; D002455:Cell Division; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D015851:Interleukin-7 / Q000502:physiology; D017154:Stromal Cells / Q000502:physiology
D015703:Antigens, CD; D018952:Antigens, CD34; D015815:Cell Adhesion Molecules; D015851:Interleukin-7