ISSN:0021-9541    

DOI:10.1002/jcp.1041130404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe stem cell concept continues to be very useful both for studies on cellular differentiation and for studies on neoplasia. At present the concept is being enlarged to include consideration of a new aspect: stem cell genetics, at the molecular level. Some questions are still to be answered. What is the basis for genetic regulation of “commitment,” that is, the transition from pluripotent stem cells to committed progenitor cells? Does neoplasia involve changes in the genetic material of hemopoietic stem cells? To illustrate the ways in which genetic approaches may be used to provide new answers to these important questions, a minimal model of commitment at the molecular level is presented. The model is based on the assumption that movable genetic elements may play a hitherto‐unsuspected role in the early stages of stem cell differentiation. It provides a simple explanation for the apparent close association between loss of potential for stem cell renewal and commitment. The possibility that analogous movable genetic elements may be involved in both the development of neoplastic cells and the differentiation of normal cells is also discussed. The need for caution in interpreting evidence for apparent differences in the genetic material of normal and neoplastic cells is str

ISSN:0021-9541    

DOI:10.1002/jcp.1041130405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe 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

ISSN:0021-9541    

DOI:10.1002/jcp.1041130406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractCells obtained from in vitro colonies expressing multiple hemopoietic lineages (mixed‐erythroid colonies) have been shown to produce secondary mixed‐erythroid colonies. When individual mixed‐erythroid colonies are studied, considerable variation has been observed in the capacity to produce secondary mixed‐erythroid colonies. That this heterogeneity in self‐renewal capacity may be an intrinsic property of the primary mixed‐erythroid colonies has been shown by the ability to fractionate fetal liver mixed‐erythroid colony‐forming cells with high and low levels of secondary colony formation. In addition mixed‐erythroid colony‐forming cells obtained from spleens consistently produce higher numbers of secondary mixed‐erythroid colonies (up to 250 secondary mixed‐erythroid colonies per primary mixed‐erythroid colony) than bone marrow‐derived mixed‐erythroid colonies (no secondary mixed‐erythroid colonies obtained) suggesting that external factors may predetermine the ability of primary mixed‐erythroid colony‐forming cells to self‐renew in vitro. The ability of supernatants obtained from long‐term marrow cultures to enhance secondary colony formation by bone marrow‐derived mixed‐erythroid colony‐forming cells raises the possibility of defining the nature of the proposed external

ISSN:0021-9541    

DOI:10.1002/jcp.1041130407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

ISSN:0021-9541    

DOI:10.1002/jcp.1041130408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

ISSN:0021-9541    

DOI:10.1002/jcp.1041130409

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe growth of large, compact megakaryocyte colonies in cultures of human bone marrow is promoted by fresh human plasma and medium conditioned by phyto‐hemagglutinin stimulated leukocytes (PHA‐LCM). These colonies are typically composed of large cells with translucent cytoplasma, surrounded by a highly refractile border. In addition, they may also contain smaller cells of similar morphology. Independent of their size, all cells react positively with antibodies directed against human factor VIII antigen. The frequency of megakaryocyte colonies may vary for different individuals from 1–35 colonies per 105mononuclear bone marrow cells. The observed linear relationships between the number of cultured cells and the frequency of colonies suggests a single cell origin. The described culture conditions also support the development of a larger megakaryocyte component within multilineage mixed colonies, so that it will now be feasible to investigate the mechanisms involved in directing pluripotent cells towards megakary‐ocyto

ISSN:0021-9541    

DOI:10.1002/jcp.1041130410

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe murine myelomonocytic leukemia WEHI‐3B exists as differentiation‐inducible (D+) and noninducible (D−) cell lines. Both lines produce a CSF species that stimulates exclusively the formation of neutrophil granulocyte colonies. This G‐CSF copurifies with a mast cell growth factor but can be separated from M‐ and GM‐CSF. NZB bone marrow is unresponsive to G‐CSF stimulation. WEHI‐3B D+cells can be induced to terminal granulocyte differentiation by a factor present in murine and human postendotoxin serum that is different from G‐CSF present in WEHI‐3B D+or D−CM since the latter has little or no leukemia differentiation‐inducing activity. Endotoxin treatment ofC. parvumprimed mice leads to simultaneous induction of serum activities with selective action on myeloid leukemic cells, a serum differentiation inducing activity and a leukemic colony inhibitory activity. These factors act synergistically to block leukemic stem cell self‐renewal. The results suggest that a variety of inducible factors may have potent and select

ISSN:0021-9541    

DOI:10.1002/jcp.1041130411

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractMolecules in conditioned medium from stimulated lymphocyte populations or from certain cell lines are known to stimulate cells committed to various hemopoietic lineages as well as pluripotential cells to form colonies in culture. In this study, the relationship between molecules active on pluripotential cells and early cells committed to granulocyte, macrophage, megakaryocyte, or red cell production was explored using techniques of chemical separation. After separation on the basis of charge, or after sequential purification using methods of high resolving power based on hydrophobicity and size, these activities remained associated with one another. The observations provide support for a model which proposes that pluripotential hemopoietic precursor cells as well as their early committed progeny may all be responsive to a single lineage‐indifferent factor. Responsiveness to “lineage‐specific” factors such as erythropoietin is proposed to be a feature only of later cells after they have made the appropriate receptors as part of their differentiation

ISSN:0021-9541    

DOI:10.1002/jcp.1041130412

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractLong‐term cultures of marrow cells from ten normal subjects and three patients with polycythemia vera were established to compare normal and neoplastic hemopoiesis in vitro. Suspended cells were removed periodically from the cultures and assayed for their content of various colony‐forming cells, including erythroid colony‐ and burst‐forming cells (CFU‐E and BFU‐E), granulocyte/macrophage colony‐forming cells (CFU‐C), and “mixed cell” colony progenitors (CFU‐CEMM). To determine if mixed cell colonies arise from a single progenitor, we used the cellular mosaicism conferred by X‐chromosome inactivation. The isoenzymes of glucose‐6‐phosphate dehydrogenase (G‐6‐PD) were used as markers of the mosaicism. Preliminary results suggest that these colonies are clonal only at low plating densities. The G‐6‐PD system was also used to determine whether selection or “drift” occurs in continuous long‐term cultures. The ratios of G‐6‐PD isoenzyme types in pooled colonies from cultures of two normal heterozygotes remained similar, indicating stable cultures. Long‐term cultures of normal marrow and marrow from the patients with polycythemia vera maintained BFU‐E for a mean of 8.7 (± 0.6) and 12.5 (± 0.5) weeks (P = 0.03), respectively. The fractions of total BFU‐E detected as endogenous erythroid colonies remained similar over the culture period. These results demonstrate that (1) hemopoiesis in polycythemia vera can be analyzed in long‐term culture; (2) polycythemia vera marrow grows as well or better than normal in long‐term culture; and (3) the proportion of the neoplastic clone in polycythemia vera represented by endogenous erythroid colony growth is unchanged over time, suggesting

ISSN:0021-9541    

DOI:10.1002/jcp.1041130413

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY