Hemopoietic Colony Studies

Abstract

In heavily irradiated mice, bone marrow regeneration of either endogenous or exogenous origin was shown to occur in discrete foci comparable to the more intensively studied spleen colonies. The number of endogenous bone marrow colonies was inversely related to dose of whole body X-irradiation. Endogenous marrow colonies were found after higher doses of irradiation than were endogenous spleen colonies. Most of them were granulocytic in nature. Exogenous bone marrow colonies in lethally irradiated mice injected with bone marrow cells were proportional in number to the dose of cells injected, appeared at a time comparable to spleen colonies like which, at 7 or 8 days, they were of single differentiated cell line, either granuloid or erythroid or megakaryocytic, with a small percentage of "mixed" colonies. Whereas erythroid colonies outnumber granuloid colonies in spleen, either in situ or subcutaneously transplanted (E:G colony ratio of about 3.5), granuloid colonies outnumber erythroid in bone marrow (E:G colony ratio of about 0.7). The characteristic E:G colony ratios of spleen and marrow appear more likely to be the result of a hemopoietic organ stromal influence on pluripotent colony forming units (CFU's) than of selective lodgment of committed (unipotent) granuloid and erythroid CFU's in bone marrow and spleen, respectively, as indicated by the following. Bone marrow stem cells (CFU) which had reseeded the marrow cavity of irradiated primary recipients 18–24 hr earlier, were reharvested and retransplanted intravenously into irradiated secondary hosts. The E:G colony ratio of the colonies formed in the spleen of the secondary hosts was typical of primary spleen colonies (2.8), that of the colonies formed in the marrow cavity was typical of bone marrow colonies (0.6). Pieces of marrow stroma containing reseeded CPU's from the contralateral femur of these same primary recipients were implanted by trocar directly into the spleens of other irradiated secondary recipients. Those CPU's that developed in the intrasplenic-implanted marrow stroma yielded an. E:G colony ratio of 0.1. Those that migrated into the contiguous and remote portions of the spleen gave E:G colony ratios of 2.9 and 2.4, respectively. Irradiated marrow stroma and normal spleen CPU's (a 1 mm cube of spleen) were loaded into the same trocar and implanted directly into the spleens of irradiated mice. The spleen CFU's that migrated into the implanted marrow stroma yielded five granuloid and two mixed colonies. The larger number that developed in the host spleen yielded an E:G colony ratio of 2.9 or higher. Of those 19 mixed colonies that bridged the junction of spleen and implanted marrow stroma in each of the above two experiments, in every case, the erythroid portion of the colony was in the splenic stroma, the granuloid portion was in the marrow stroma.

Promotion of survival and proliferation by interleukin 3, fcil‐ligand and erythropoietin on early and late appearing spleen colony forming units in culture

“…Pluripotent stem cells are thought to have a capacity for self-renewal and differentiation into all hematopoietic lineages and to play an important role in the long-term reconstitution of hematopoiesis after bone marrow transplantation. Improvement of experimental methods, such as the murine spleen colony assay and hemopoietic cell culture, has provided useful models to clarify the kinetics of pluripotent stem cells; some of the early studies emphasized the importance of the microenvironment in the proliferation and differentiation of stem cells rather than circulating humoral factors [ 1,2]. Lord and Wright, and Tejero et al suggested that the proliferation rate of the colony forming units in spleen (CFU-S) in bone marrow cells was controlled by locally produced stimulatory and inhibitory factors [3,4].…”

The GOD of Hematopoietic Stem Cells: A Clonal Diversity Model of the Stem Cell Compartment

“…The major themes of these theories are intrinsic vs. instructive. The instructive models, [17][18][19] postulate that the microenvironment educates HSC to change. The models of intrinsic regulation of HSC diversity can be subdivided into stochastic and deterministic theories.…”

Extramedullary hematopoiesis in the adult mouse liver is associated with specific hepatic sinusoidal endothelial cells

“…lar contact that regulates in vivo and in vitro hematopoieThese results suggest that LEC-1, but not LEC-2, provide an sis. [8][9][10] In vivo, it has been shown that bone marrow (BM) appropriate hematopoietic microenvironment for supporting stroma determines the differentiation of hematopoietic the proliferation and differentiation of primitive hematopoicells. 8,9 In vitro, Dexter et al established a system of longetic cells.…”

“…[8][9][10] In vivo, it has been shown that bone marrow (BM) appropriate hematopoietic microenvironment for supporting stroma determines the differentiation of hematopoietic the proliferation and differentiation of primitive hematopoicells. 8,9 In vitro, Dexter et al established a system of longetic cells. This could explain the anatomical restriction of term BM culture using BM stroma cells; the system was able hematopoietic cells for growing in LEC-1 domains during liver to support the differentiation and proliferation of hematopoiextramedullary hematopoiesis.…”

“…lar contact that regulates in vivo and in vitro hematopoieThese results suggest that LEC-1, but not LEC-2, provide an sis. [8][9][10] …”