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Regulation of pluripotent stem cell proliferation and differentiation: The role of long‐range humoral factors
Author(s) -
Tubiana Maurice,
Frindel Emilia
Publication year - 1982
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041130406
Subject(s) - bone marrow , haematopoiesis , spleen , in vivo , biology , in vitro , immunology , stem cell , microbiology and biotechnology , pharmacology , andrology , biochemistry , medicine
The proliferative status of the hemopoietic pluripotential stem cells (CFU‐S) is controlled by inhibitors and stimulators, which have been studied by an in vivo‐in vitro technique. Inhibitors protect CFU‐S during iterative administration of cycle specific drugs. Among stimulators are long‐range humoral factors that are released by bone marrow following irradiation or drug administration. After the same treatment, bone marrow also releases a long‐range humoral factor that increases the rate of differentiation of CFU‐S, probably in order to compensate for the depletion of the maturing compartment. This differentiation is qualitatively different from normal differentiation. When the bone marrow of mice treated with Ara‐C is transplanted to lethally irradiated mice, the total number of nodules remains constant; however the number of erythroid (E) colonies in the spleen is significantly increased, while the number of granulocytic (G) colonies is significantly decreased, and the number of mixed colonies is slightly decreased. Similar observations for E and G colonies are made when normal bone marrow is injected into lethally irradiated mice following in vitro incubation with humoral factors released by cytosine‐arabinoside (Ara‐C)‐treated mice. In both cases most splenic colonies contain CFU‐S and GM‐CFC, even when they appear histologically E colonies. After irradiation or iterative administration of Ara‐C the E/G ratio is decreased. The factors involved, pluripoietins, are released by both bone marrow and spleen and are found in the serum of treated mice. The mechanism by which they act is unknown; however two hypotheses can be made: (a) Modulation of differentiation potential towards only one of the cell lineages. During 6 to 7 days after Ara‐C administration the determination of CFU‐S is modified. However this restriction to erythroid determination is temporary. This hypothesis is compatible with the “hemopoietic inductive model,” but microenvironment is not playing any role. (b) Specific inhibition or stimulation of the committed stem cells to which the CFU‐S having received the “message” gives birth. This information lasts during one week but disappears when the cells are plated in vitro. Whatever the mechanism, the primary events occur at CFU‐S level and the information is transmitted to the descendants, showing that humoral factors can channel the differentiation pathways.