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Results for “Multipotent Stem Cells”

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PubMed1991

Detection of burst-promoting activity in spleens of myeloproliferative sarcoma virus-infected mice using serum-free cultures.

Myeloproliferative syndrome was induced in adult DBA/2 mice by inoculation with myeloproliferative sarcoma virus (MPSV) and Friend murine leukemia virus (F-MuLV) as a helper virus. On day 26 after infection, the spleen weighed a maximum of 2.0 g (about 30 times the control weight). Assay of multipotent stem cells in vitro showed that the more enlarged spleens contained an increased number and concentration of mixed colony-forming units (CFU-mix) (at maximum, 11 times higher than the control). When the supernatant of cultured spleen cells was added to a serum-free bone marrow cell culture with or without erythropoietin (Epo) for detection of burst-promoting activity (BPA), it enhanced erythroid mixed colony (E-mix) formation only in the presence of Epo (p less than 0.05). Even when addition of Epo was delayed, it still induced a significant number of E-mix (p less than 0.05). These findings rule out a mimic effect of Epo resembling BPA and indicate the presence of BPA in the spleen. The culture supernatant also supported the proliferation of interleukin 3 (IL-3)-dependent 32Dcl cells. Therefore, although purification of the BPA substance has not yet been accomplished, BPA in the supernatant seems to depend on the presence of IL-3, which is known to be one of the factors stimulating multipotent hemopoietic stem cells. The presence of BPA- or CFU-mix-stimulating activity in the spleen after infection might be responsible for the development of panmyelosis, which is a characteristic of MPSV-induced myeloproliferative syndrome.

Animals↗

PubMed1989

Cellular interactions between 3T3 cells and interleukin-3-dependent multipotent haemopoietic cells: a model system for stromal-cell-mediated haemopoiesis.

With the aid of a multipotent stem cell line (FDCP-mix cells) co-cultured with either normal or irradiated Swiss 3T3, cellular interactions between stromal cells and haemopoietic stem cells were studied by electron microscopy and time-lapse video microscopy. When cultured in the presence of interleukin 3 (IL-3) but in the absence of stromal cells, the FDCP-mix cells have a characteristic blast morphology. In the absence of IL-3, the cells die unless they are co-cultured with marrow stromal cells or 3T3 cells. In the latter case, they attach, proliferate, and differentiate on both normal and irradiated Swiss 3T3 cell layers without the addition of extrinsic growth factor (IL-3). At the initial attachment sites of these two cell lines, cellular recognition seemed to be mediated by the formation of microvillus cytoplasmic projections and extracellular matrix. These areas may well be the sites of plasma-membrane-bound signalling/adhesional molecules between the interacting cells.

Animals↗

PubMed2004

Tissue engineering with muscle-derived stem cells.

Tissue engineering and cell therapy approaches aim to take advantage of the repopulating ability and plasticity of multipotent stem cells to regenerate lost or diseased tissue. Researchers continue to investigate stem cells in mature tissues and demonstrate the potential ability of organ-specific cells to differentiate into multiple lineages. One stem cell that displays such promise is the muscle-derived stem cell (MDSC). Data supporting the existence of MDSCs have emerged as part of investigations to improve myoblast cell transplantation for the treatment of muscular dystrophies. As these efforts continue, the potential for MDSC-based therapy for other musculoskeletal injuries, as well as for cardiac and smooth muscle injuries, is currently being explored.

Animals↗

PubMed2003

SHED: stem cells from human exfoliated deciduous teeth.

To isolate high-quality human postnatal stem cells from accessible resources is an important goal for stem-cell research. In this study we found that exfoliated human deciduous tooth contains multipotent stem cells [stem cells from human exfoliated deciduous teeth (SHED)]. SHED were identified to be a population of highly proliferative, clonogenic cells capable of differentiating into a variety of cell types including neural cells, adipocytes, and odontoblasts. After in vivo transplantation, SHED were found to be able to induce bone formation, generate dentin, and survive in mouse brain along with expression of neural markers. Here we show that a naturally exfoliated human organ contains a population of stem cells that are completely different from previously identified stem cells. SHED are not only derived from a very accessible tissue resource but are also capable of providing enough cells for potential clinical application. Thus, exfoliated teeth may be an unexpected unique resource for stem-cell therapies including autologous stem-cell transplantation and tissue engineering.

Animals↗

PubMed2001

[Lineage-switching by pluripotent cells derived from adults].

When proceeding normally, embryonic morphogenesis begins with germ layer formation through the process of gastrulation. Each primordial germ layer gives rise to a particular set of lineages. Until recently, it was considered that fate switches between germ layers were impossible. In the last two or three years however, a fair number of such switches have been described (Table I), the most spectacular of which entails the differentiation of neural stem cells into various derivatives. This unexpected plasticity opens important prospects for cell therapy. Stem cells, which are the cells that display this plasticity, are defined by the two properties of self renewal and pluripotency. They are set apart during ontogeny and are responsible for maintaining the homeostasis of a tissue. This notion, first established in the case of hematopoietic stem cells was later extended to other fast renewing cells, such as those in the intestinal epithelium or epidermis, and more recently to cells reputedly non-renewable, i.e. neurons. A new strategy has been described, which has the interesting feature that it can be applied to the isolation of stem cells from various lineages. It consists in sorting out cells on the basis of the efflux of Hoechst 33342 dye (Goodell et al., 1996). When a cell suspension stained with this dye is examined under two distinct wave lengths, a "side population" (SP), characterized by weak fluorescence, can be identified and sorted out. The dye efflux property of these cells is due to the activity of the mdr (multidrug resistance) gene, which encodes a protein responsible for the building of a canal which serves to extrude toxins from the cells. A means of distinguishing a truly multipotent stem cell from a progenitor committed to a specific lineage has been reported. This consists in the expression of the Pax7 gene. Pax7-/- mouse muscles have no satellite cells, i.e. they miss the cells normally responsible for the regeneration of muscle. In contrast they do have an SP population. These SP cells are incapable of differentiating into muscle, but give rise to 10 times more hematopoietic colonies, when cloned in vitro, than SP cells from wild type muscle do. Thus Pax7 appears to be a commitment gene, in the absence of which stem cells cannot become specified to the muscle lineage. As a conclusion, this review emphasizes various features of the recent findings: 1) the unexpected plasticity uncovered in recent years is restricted to the stem cells of each tissue; 2) the switch in phenotype has to be "forced" on these stem cells by drastic experimental conditions enforced in the host: often sublethal irradiation is superimposed on a genetic deficiency. Progress in this field, concerning both conceptual and applied aspects, will require the identification of the factors characterizing the niches which promote integration and fate switches of stem cells, probably a combination of growth factors and intercellular interactions. Finally a key issue, before any therapeutical applications can be considered, is how to control the proliferation of transplanted stem cells in their new environment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Coexpression of platelet-derived growth factor alpha and beta receptors on medulloblastomas and other primitive neuroectodermal tumors is consistent with an immature stem cell and neuronal derivation.

Medulloblastomas and related childhood primitive neuroectodermal tumors (PNET) are currently thought to originate from a multipotent stem cell that can give rise to a variety of different tumor types, representing different lines of differentiation and stages of maturation of the original stem cell. The proliferation and differentiation of different cell types in the central nervous system are influenced by growth factors, such as platelet-derived growth factor (PDGF). In this study, we investigated the expression of the two types of PDGF receptors, alpha and beta, on 14 cases of PNET by immunohistochemistry and in situ hybridization. To characterize the tumor cells according to their differentiation and maturation, we performed immunohistochemistry with Ab against several members of the intermediate filament family, such as neurofilament, glial fibrillary acidic protein, vimentin, and the embryonal marker nestin. For the cerebral PNET, we found that the phenotype of multidirectional differentiation (with coexpression of neurofilament, glial fibrillary acidic protein, vimentin, and in some cases nestin) was associated with the expression of both PDGF alpha and beta receptors on the tumor cells. Medulloblastomas (i.e., cerebellar PNET), however, often showed the phenotype of partially committed neuron-like precursor cells, and this was associated with the predominant expression of PDGF alpha receptors on the tumor cells. Our findings show that the PDGF alpha receptor, previously known to play a role in the normal development of cells of the glial lineage, either exclusively or in combination with the PDGF beta receptor, is expressed on tumor cells of neuronal derivation. This "aberrant" expression of PDGF alpha receptors on PNET may reflect a feature of the malignant phenotype of these tumors. Further studies are needed to study the biologic effects of PDGF-A and its receptor in PNET.

Brain Neoplasms↗

PubMed2000

Regulation of neuronal differentiation in human CNS stem cell progeny by leukemia inhibitory factor.

The generation of diverse types of neural cells during development occurs through the progressive restriction of the fate potential of neuroepithelial progenitor cells. This process is controlled by factors intrinsic and extrinsic to the cell. While the effect of extrinsic cues on multipotent stem cells of the murine central nervous system (CNS) is becoming clearer, little is known of neural stem cells of human origin. We sought to establish the roles played by two cytokines, leukemia inhibitory (LIF) and ciliary neurotrophic factor (CNTF), and by nerve growth factor (NGF) and platelet-derived growth factor (PDGF) in regulating neuronal and astroglial differentiation in cultured embryonic diencephalic human stem cells. While NGF did not influence either neuronal or glial formation, PDGF surprisingly decreased the percentage of stem cell-generated neurons, an effect opposite to that observed in murine progenitors. Furthermore, while we confirmed the known ability of LIF and CNTF to support astroglial differentiation, we also observed that, in contrast with their murine counterparts, the fraction of CNS stem cell-generated neurons in human cultures was enhanced twofold in the presence of both cytokines. These findings highlight important differences between humans and rodents in regard to the way epigenetic cues regulate the function of neural stem cells.

Astrocytes↗

PubMed1998

Development of the avian iris and ciliary body: mechanisms of cellular differentiation during the smooth-to-striated muscle transition.

The avian iris and ciliary body undergoes a transition from smooth-to-striated muscle during embryonic development. Using antibodies specific for smooth muscle-specific alpha-actin and myosin heavy chain, we confirm that a smooth-to-striated muscle transition occurs between E8 and E17 in both iris and ciliary body of the chick. To study the mechanisms regulating the transition in muscle type, we analyzed the fate of quail clones derived from E7 iris cells. When cells were cloned alone, 45/71 colonies differentiated into smooth muscle and 10/71 became striated muscle. None of the colonies were mixed with respect to muscle phenotype, indicating a lack of pluripotent stem cells. Furthermore, clones giving rise to nonstriated muscle could not be forced to incorporate into myotubes when cocultured with chick myocytes. Clones grown in coculture with chick embryo fibroblasts or E11 iris cells had very high cloning efficiencies (>98%). Significantly more clones differentiated into striated muscle when cocultured with E11 cells (60/156) than when cocultured with fibroblasts (29/108). This was due to an increased recruitment of undifferentiated cells into striated muscle, rather than a change in the percentage of cells differentiating into smooth muscle. In vivo and in vitro, various smooth and striated muscle-specific markers including contractile proteins, acetylcholine receptor subtypes, and transcription factors were colocalized in cells. Although our data argue against a multipotent stem cell for smooth and striated muscle cells, they cannot exclude a role for transdifferentiation. Cumulatively these results suggest that both smooth muscle and migratory myoblasts contribute to the development of myotubes in the avian iris and that this process is regulated in a non-cell-autonomous fashion by locally generated signals.

Acetylcholine↗

PubMed2001

Transforming growth factor beta 1 mediates cell-cycle arrest of primitive hematopoietic cells independent of p21(Cip1/Waf1) or p27(Kip1).

The regulation of stem cell proliferation is a poorly understood process balancing rapid, massive blood cell production in times of stress with maintenance of a multipotent stem cell pool over decades of life. Transforming growth factor beta 1 (TGF-beta 1) has pleiotropic effects on hematopoietic cells, including the inhibition of primitive cell proliferation. It was recently demonstrated that the cyclin-dependent kinase inhibitors, p21(Cip1/Waf1) (p21) and p27(Kip1) (p27), can inhibit the proliferation of hematopoietic stem cells and progenitor cells, respectively. The relation of TGF-beta 1 stimulation to p21 and p27 was examined using a fine-mapping approach to gene expression in individual cells. Abundant TGF-beta 1 expression and p21 expression were documented in quiescent, cytokine-resistant hematopoietic stem cells and in terminally differentiated mature blood cells, but not in proliferating progenitor cell populations. TGF-beta 1 receptor (T beta R II) was expressed ubiquitously without apparent modulation. Cell- cycle-synchronized 32D cells exposed to TGF-beta 1 demonstrated a marked antiproliferative effect of TGF-beta 1, yet neither the level of p21 mRNA nor the protein level of either p21 or p27 was altered. To corroborate these observations in primary cells, bone marrow mononuclear cells derived from mice engineered to be deficient in p21 or p27 were assessed. Progenitor and primitive cell function was inhibited by TGF-beta 1 equivalently in -/- and +/+ littermate controls. These data indicate that TGF-beta 1 exerts its inhibition on cell cycling independent of p21 and p27 in hematopoietic cells. TGF-beta 1 and p21 or p27 participate in independent pathways of stem cell regulation, suggesting that targeting each may provide complementary strategies for enhancing stem or progenitor cell expansion and gene transduction.

Adult↗

PubMedDate not supplied

SOX2, a persistent marker for multipotential neural stem cells derived from embryonic stem cells, the embryo or the adult.

Multipotent neural stem cells are present throughout the development of the central nervous system (CNS), persist into adulthood in defined locations and can be derived from more primitive embryonic stem cells. We show that SOX2, an HMG box transcription factor, is expressed in multipotent neural stem cells at all stages of mouse ontogeny. We have generated transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of the endogenous locus-regulatory regions of the Sox2 gene to prospectively identify neural stem/progenitor cells in vivo and in vitro. Fluorescent cells coexpress SOX2 protein, and EGFP fluorescence is detected in proliferating neural progenitor cells of the entire anterior-posterior axis of the CNS from neural plate stages to adulthood. SOX2-EGFP cells can form neurospheres that can be passaged repeatedly and can differentiate into neurons, astrocytes and oligodendrocytes. Moreover, prospective clonal analysis of SOX2-EGFP-positive cells shows that all neurospheres, whether isolated from the embryonic CNS or the adult CNS, express SOX2-EGFP. In contrast, the pattern of SOX2-EGFP expression using randomly integrated Sox2 promoter/reporter construct differs, and neurospheres are heterogeneous for EGFP expression. These studies demonstrate that SOX2 may meet the requirements of a universal neural stem cell marker and provides a means to identify cells which fulfill the basic criteria of a stem cell: self-renewal and multipotent differentiation.

Animals↗

PubMed2004

A dermal niche for multipotent adult skin-derived precursor cells.

A fundamental question in stem cell research is whether cultured multipotent adult stem cells represent endogenous multipotent precursor cells. Here we address this question, focusing on SKPs, a cultured adult stem cell from the dermis that generates both neural and mesodermal progeny. We show that SKPs derive from endogenous adult dermal precursors that exhibit properties similar to embryonic neural-crest stem cells. We demonstrate that these endogenous SKPs can first be isolated from skin during embryogenesis and that they persist into adulthood, with a niche in the papillae of hair and whisker follicles. Furthermore, lineage analysis indicates that both hair and whisker follicle dermal papillae contain neural-crest-derived cells, and that SKPs from the whisker pad are of neural-crest origin. We propose that SKPs represent an endogenous embryonic precursor cell that arises in peripheral tissues such as skin during development and maintains multipotency into adulthood.

Adult↗

PubMed2006

Coaxing bone marrow stromal mesenchymal stem cells towards neuronal differentiation: progress and uncertainties.

Multipotent adult stem cells capable of developing into particular neuronal cell types have great potential for autologous cell replacement therapy for central nervous system neurodegenerative disorders and traumatic injury. Bone marrow-derived stromal mesenchymal stem cells (BMSCs) appear to be attractive starting materials. One question is whether BMSCs could be coaxed to differentiate in vitro along neuronal or glial lineages that would aid their functional integration post-transplantation, while reducing the risk of malignant transformation. Recent works suggest that BMSCs could indeed be differentiated in vitro to exhibit some cellular and physiological characteristics of neural cell lineages, but it is not likely to be achievable with simple chemical treatments. We discussed recent findings pertaining to efforts in neuronal differentiation of BMSCs in vitro, and results obtained when these were transplanted in vivo.

Animals↗

PubMed1990

Systematic analysis of the ability of stromal cell lines derived from different murine adult tissues to support maintenance of hematopoietic stem cells in vitro.

Hematopoietic stem cells interact with a complex microenvironment both in vivo and in vitro. In association with this microenvironment, murine stem cells are maintained in vitro for several months. Fibroblast-like stromal cells appear to be important components of the microenvironment, since several laboratories have demonstrated that cloned stromal cell lines support hematopoiesis in vitro. The importance of the tissue of origin of such cell lines remains unknown, since systematic generation of stromal cell lines from adult tissues has never been accomplished. In addition, the capacity of stromal cell lines to support reconstituting stem cell has not been examined. We have previously described an efficient and rapid method for the immortalization of primary bone marrow stromal cell lines (Williams et al., Mol. Cell. Biol. 8:3864-3871, 1988) which can be used to systematically derive cell lines from multiple tissues of the adult mouse. Here we report the immortalization of primary murine lung, kidney, skin, and bone marrow stromal cells using a recombinant retrovirus vector (U19-5) containing the simian virus large T antigen (SV40 LT) and the neophosphotransferase gene. The interaction of these stromal cells with factor-dependent cells Patterson-Mix (FDCP-Mix), colony forming units-spleen (CFU-S), and reconstituting hematopoietic stem cells was studied in order to analyze the ability of such lines to support multipotent stem cells in vitro. These studies revealed that stromal cell lines from these diverse tissues were morphologically and phenotypically similar and that they quantitatively bound CFU-S and FDCP-Mix cells equally well. However, only those cell lines derived from bone marrow-supported maintenance of day 12 CFU-S in vitro. One lung-derived stromal cell line, ULU-3, supported the survival of day 8 CFU-S, but not the more primitive CFU-S12. A bone marrow-derived stromal cell line, U2, supported the survival of long-term reconstituting stem cells for up to 3 weeks in vitro as assayed by reconstitution 1 year post-transplant. These studies suggest that adherence of HSC to stromal cells is necessary but not sufficient for maintenance of these stem cell populations and that bone marrow provides specific signals relating to hematopoietic stem cell survival and proliferation.

Actins↗

PubMed1995

Origin of the avian neural crest.

Neural crest cells are derived from a population of multipotent stem cells within the neural tube. They emerge shortly after neural tube closure, migrate extensively in the embryo and localize in numerous sites, where they differentiate into neurons and glia of the peripheral nervous system, cartilage and bone of the face, melanocytes and various other cell types. This review summarizes recent experiments from our laboratory delineating the origin and lineage of avian neural crest cells. Neural crest cells arise from the ectoderm, which also gives rise to presumptive epidermal, placodal and neural tube cells. Fate mapping experiments have demonstrated that the neural crest arises at the juncture between presumptive epidermis and the neural plate. Inductive interactions between these two early tissues can generate neural crest cells, suggesting that signals travel through the epidermis to generate neural crest cells prior to neural tube closure. Injection of lineage tracer into individual cells reveals that a single neural fold can form all ectodermal derivatives (i.e., epidermis, neural tube, neural crest). Even after neural tube closure, neuroepithelial cells have the capacity to form multiple neural crest and neural tube derivatives, including both dorsal and ventral phenotypes, suggesting that neural tube and neural crest cells share a common precursor. Further evidence that neural crest and neural tube cells are intimately related comes from experiments in which the cranial neural folds are ablated. The remaining neural tube cells have the capacity to regulate, at least for a limited time, to compensate for missing neural crest cells. These experiments suggest that the early neuroepithelium has no clear segregation with respect to the neural tube or neural crest. With time, dorsalizing and ventralizing signals may cause neural tube cells to acquire specific cell fates.

Animals↗

PubMed1993

Origins of neural crest cell diversity.

The neural crest is a population of migratory cells, arising from the ectoderm, that invades many sites within the embryo and differentiate into a variety of diverse cell types. Pigment cells, most cells of the peripheral nervous system, adrenal medullary cells, and some cranial cartilage are derived from the neural crest. Despite a wealth of knowledge concerning their pathways of migration and vast array of derivatives, little is known about the formation of neural crest cells or their acquisition of positional identity. This review focuses on the origin of neural crest cells from the ectoderm and the generation of differences in neural crest cell fates along the rostrocaudal axis. In addition, we consider the role of temporal restriction in the developmental potential of premigratory neural crest cells. While evidence for the existence of multipotent stem cells is strong, some experiments also suggest that there may be heterogeneity among neural crest cell precursors, perhaps due to differences in origin, that might explain commitment events occurring early in neural crest development.

Animals↗

PubMed1991

[Rearrangement and expression of bcr-abl genes in CML and ALL].

We have carried out the molecular and cell-biological analysis on Ph1-positive leukemias in this study. Five out of nine Ph1-positive ALL cases showed molecular rearrangement within the classical bcr sequence (or M-bcr), similar as those in 47 CML cases. We examined 4 cases of Ph1-positive ALL presenting no rearrangement of M-bcr and found that, in 2 of 4 cases, one showed the breakpoint in a 5 kb segment of the bcr gene first intron (bcr-2) and the other in bcr-1, 16 kb upstream of bcr-2. Ph1-positive ALL frequently showed biphenotypical or biclonal phenotypes of myeloid and lymphoid lineages. Furthermore, we demonstrated the ability of two Ph1-positive ALL cell lines to differentiate into monocytic lineage in vitro, thus suggesting the possibility that these Ph1-positive ALL cells might reside on the stage of multipotent stem cell along the hematopoietic cell differentiation. Two out of 31 CML cases showed the mutations of the ras genes by the polymerase chain reaction; one case in the crisis phase and the other in the chronic phase. However, no mutations of the fms genes was detected. Two cases in the crisis phase of 24 CML patients (11 cases in the chronic phase and 13 cases in the crisis phase) contained rearrangements of the p53 gene by Southern analysis. Furthermore, the transcriptional alteration was found in 2 CML-BC and 2 CML-BC derived cell lines' samples, suggesting a important role of the p53 gene in the transformation of CML into the crisis phase.

Chromosome Fragility↗

PubMed1995

[Gene therapy for hereditary and acquired human diseases].

Cystic Fibrosis (CF) and AIDS are primary candidate disorders to be treated by gene therapy, owing to their lethality and the absence of efficient clinical treatments. Treatment of CF by gene therapy will require the transfer of the functional CFTR cDNA into the diseased human airway epithelia since mutations within the CFTR gene are responsible for CF. We have therefore cloned the human CFTR cDNA and developed a recombinant E1-deleted adenoviral vector carrying a CFTR expression cassette. We demonstrated in vitro the ability of this vector to efficiently transduce human lung cells isolated from CF patients and to correct their phenotype. Efficient in, vivo delivery of the CFTR cDNA to the airways of cotton rats and rhesus monkeys was also obtained and no dissemination of the recombinant viral vector in other tissues than the airways was observed. We have therefore designed a phase I clinical trial involving CF patients. In contrast to the monogenic CF disease, the mechanisms of AIDS pathogenesis still remain poorly understood. Such limited knowledge of the disease constitutes a serious restriction to the development of a rational gene therapy strategy for AIDS. Since HIV, the causative agent of AIDS, predominantly infects cells of the hematopoietic system, pluri- or multipotent stem cells may constitute potential targets for the introduction of a foreign anti-HIV gene that will inhibit HIV replication and/or spread. Reimplantation of the genetically modified stem cells into asymptomatic HIV-infected patients should theoretically allow the repopulation of the host's immune system with mature CD4+ cells expressing novel molecules that interfere with viral replication, thus slowing the progression of AIDS. We identified several new transdominant inhibitors derived from the viral TAT and REV proteins and showed their ability to confer to human CD4 lymphocytes resistance against HIV1 infection. Retroviral vectors carrying these potential therapeutic genes have been developed and are currently being tested in vivo in newly developed transgenic animal models, in humanized SCID mice and in macaques.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Erythrocyte replacement precedes leukocyte replacement during repopulation of W/Wv mice with limiting dilutions of +/+ donor marrow cells.

The severe macrocytic anemia of the stem-cell-deficient W/Wv mouse is alleviated by intravenous injection of normal marrow cells. Donor cells replace the host erythrocytes, but the fate of the more labile blood components, such as granulocytes and platelets, after transplantation into adult mice has not been established. In the present work, the rate of replacement of the various hemopoietic cells in W/Wv transplant recipients was examined by exploiting host-donor differences in cellular markers (hemoglobin and glucose-phosphate isomerase). Limiting dilutions of +/+ parental cells were injected into F1-hybrid W/Wv anemic mice. A dose of 10(5) donor cells was necessary for the implantation of sufficient multipotent stem cells to alleviate the anemia. Erythrocyte parameters were not significantly different from normal values, and donor cells replaced at least 90% of the host erythrocytes by 20 weeks after injection. At this time, only 10% of the nucleated leukocytes and none of the platelets were donor-derived. The percentage of donor lymphocytes, granulocytes, and platelets increased slowly thereafter but did not completely replace the host elements by 41 weeks. The maintenance of host leukocytes during rapid donor-erythrocyte replacement indicates cell-specific amplification of committed progenitors.

Anemia, Macrocytic↗