The fetal liver as an alternative stem cell source for hemolymphopoietic reconstitution

Prümmer, Otto; Fliedner, Theodor M.

doi:10.1002/stem.5530040402

Cited by 23 publications

(4 citation statements)

References 62 publications

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“…In human ontogeny, hematopoietic stem/progenitor cells occur first in the yolk sac, later in fetal liver, and then in fetal bone marrow (1,17), and transplantation of fetal liver cells has been used in a limited setting to correct hematopoietic deficiencies (18,19). Stem/progenitor cells occur in fetal blood (1,17), and human umbilical cord blood contains stem cells (20,21), so called because in colony assay in vitro they exhibit replating efficiency indicative of self-renewal, as well as multipotential (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells (20)(21)(22)(23)(24)(25)(26).…”

mentioning

confidence: 99%

Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells.

Broxmeyer

Douglas

Hangoc

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

1,065

530

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The purpose of this study was to evaluate human umbilical cord blood as an alternative to bone marrow in the provision of transplantable stem/progenitor cells for hematopoietic reconstitution. Although no direct quantitative assay for human hematopoietic repopulating cells is at present available, the granulocyte-macrophage progenitor cell (CFU-GM) assay has been used with success as a valid indicator of engrafting capability. We examined greater than 100 collections of human umbilical cord blood for their content of nucleated cells and granulocyte-macrophage, erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, in many cases both before and after cryopreservation. First it was determined that granulocyte-macrophage, erythroid, and multipotential progenitor cells remained functionally viable in cord blood untreated except for addition of anticoagulant for at least 3 days at 4 degrees C or 25 degrees C (room temperature), though not at 37 degrees C, implying that these cells could be satisfactorily studied and used or cryopreserved for therapy after transport of cord blood by overnight air freight carriage from a remote obstetrical service. Granulocyte-macrophage progenitor cells from cord blood so received responded normally to stimulation by purified recombinant preparations of granulocyte-macrophage, granulocyte, and macrophage colony-stimulating factors and interleukin 3. The salient finding, based on analysis of 101 cord blood collections, is that the numbers of progenitor cells present in the low-density (less than 1.077 gm/ml) fraction after Ficoll/Hypaque separation typically fell within the range that has been reported for successful engraftment by bone marrow cells. Another observation of practical importance is that procedures to remove erythrocytes or granulocytes prior to freezing, and washing of thawed cells before plating, entailed large losses of progenitor cells, the yield of unwashed progenitor cells from unfractionated cord blood being many times greater. The provisional inference is that human umbilical cord blood from a single individual is typically a sufficient source of cells for autologous (syngeneic) and for major histocompatibility complex-matched allogeneic hematopoietic reconstitution.

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mentioning

confidence: 99%

Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells.

Broxmeyer

Douglas

Hangoc

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

1,065

530

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“…All mice were from a mixed 129/SvJ x C57BL/6 background. FL cell chimeras were generated as previously described ( Prümmer and Fliedner, 1986 ; Tulunay et al, 1975 ). Briefly, 5–6 × 10 6 cells from the FL of E14.5 embryos were injected into the tail vain of sub-lethally irradiated (1 × 6 Gy) Rag2 -/- mice ( Shinkai et al, 1992 ) and chimeras were analyzed 8 to 10 weeks later.…”

Section: Methodsmentioning

confidence: 99%

Differential requirement of kindlin-3 for T cell progenitor homing to the non-vascularized and vascularized thymus

Moretti

Klapproth

Ruppert

et al. 2018

eLife

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The role of integrin-mediated adhesion during T cell progenitor homing to and differentiation within the thymus is ill-defined, mainly due to functional overlap. To circumvent compensation, we disrupted the hematopoietic integrin regulator kindlin-3 in mice and found a progressive thymus atrophy that is primarily caused by an impaired homing capacity of T cell progenitors to the vascularized thymus. Notably, the low shear flow conditions in the vascular system at midgestation allow kindlin-3-deficient fetal liver-derived T cell progenitors to extravasate via pharyngeal vessels and colonize the avascular thymus primordium. Once in the thymus, kindlin-3 promotes intrathymic T cell proliferation by facilitating the integrin-dependent crosstalk with thymic antigen presenting cells, while intrathymic T cell migration, maturation into single positive CD4 and CD8 T cells and release into the circulation proceed without kindlin-3. Thus, kindlin-3 is dispensable for integrin-mediated T cell progenitor adhesion and signalling at low and indispensable at high shear forces.

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“…Here we describe an alternative approach that involves that production of completely ES cell-derived fetuses by aggregating ES cells with tetraploid embryos (16). Normal fetal liver is a rich source of hematopoietic stem cells that are capable of reconstituting the hematopoietic system oflethally irradiated adult mice (17,18). We report here that ES cell-derived fetal liver from ES cell-tetraploid chimeras retains this ability, thus making it possible to bypass germ-line transmission and introduce the progeny of genetically manipulated ES cells directly into the adult hematopoietic system.…”

mentioning

confidence: 84%

Long-term reconstitution of the mouse hematopoietic system by embryonic stem cell-derived fetal liver.

Forrester

Bernstein

Rossant

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Murine embryonic stem (ES) cells are permanent blastocyst-derived cell lines capable of contributing to a wide variety of tissues, including the germ line, after injection into host blastocysts. Recently, we have shown that ES cells can produce all of the cells of the developing fetus after aggregation with developmentally compromised tetraploid embryos. Completely ES cell-derived embryos die perinatally, but the liver of these embryos is a source of entirely ES cell-derived hematopoietic progenitors. We have taken 14-to 15-day fetal liver cells from ES cell-tetraploid chimeras and reconstituted the hematopoietic system of lethally irradiated adult recipient mice. ES cell-derived hematopoietic stem cells were capable of long-term (>6 months) repopulation of irradiated recipients, and all hematopoietic cell lineages analyzed (erythrocytes, T cells, mast cells, and macrophages) were derived exclusively from ES

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The fetal liver as an alternative stem cell source for hemolymphopoietic reconstitution

Cited by 23 publications

References 62 publications

Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells.

Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells.

Differential requirement of kindlin-3 for T cell progenitor homing to the non-vascularized and vascularized thymus

Long-term reconstitution of the mouse hematopoietic system by embryonic stem cell-derived fetal liver.

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