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PubMed2006

Local signals in stem cell-based bone marrow regeneration.

The cellular basis of bone marrow (BM) tissue development and regeneration is mediated through hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Local interplays between hematopoietic cells and BM stromal cells (BMSCs) determine the reconstitution of hematopoiesis after myelosuppression. Here we review the BM local signals in control of BM regeneration after insults. Hematopoietic growth factors (HGFs) and cytokines produced by BMSCs are primary factors in regulation of BM hematopoiesis. Morphogens which are critical to early embryo development in multiple species have been added to the family of HSCs regulators, including families of Wnt proteins, Notch ligands, BMPs, and Hedgehogs. Global gene expression analysis of HSCs and BMSCs has begun to reveal signature groups of genes for both cell types. More importantly, analysis of global gene expression coupled with biochemical and biological studies of local signals during BM regeneration have strongly suggested that HGFs and cytokines may not be the primary local regulators for BM recovery, rather chemokines (SDF-1, FGF-4) and angiogenic growth factors (VEGF-A, Ang-1) play instructive roles in BM reconstitution after myelosuppression. A new direction of management of BM toxicity is emerging from the identification of BM regenerative regulators.

Bone Marrow Cells↗

PubMed1982

Early haemopoietic responses to Salmonella typhimurium infection in resistant and susceptible mice.

The response of colony forming cells in the bone marrow and spleen of resistant (CBA) and susceptible (C57BL) mice to Salmonella typhimurium infection was studied for 4 days after infection. The number and size of the colonies were assessed. The resistant strain exhibited an immediate response to challenge, sharply increasing the number of colonies to 2.5 times normal over 2-3 days after infection. In contrast the susceptible strain gave a slowly increased response to the same challenge, which never exceeded 1.2 times normal and fell to 0.8 times the normal. When mouse strains were immunized there was a clear distinction between the splenic and bone marrow cellularity. Immunization appeared to enhance the splenic cellularity in resistant mice but failed to in susceptible mice. In the bone marrow of susceptible mice, however, there was some evidence of an elevated response.

Animals↗

PubMed2003

Induction of complete remission of hypoplastic leukemia with antithymocyte globulin.

A 13-year-old boy was admitted to a local hospital because of pancytopenia. A bone marrow aspiration and biopsy revealed severely hypocellular marrow with no obvious leukemic cells. The diagnosis was severe aplastic anemia, and the patient was treated with antithymocyte globulin and cyclosporin A. A trilineage response was obtained, and the patient became transfusion-independent within 2 weeks. Two months later, the peripheral blood count normalized with an increased bone marrow cellularity. However, the patient was readmitted 5 months later for recurrence of the pancytopenia. A bone marrow aspiration revealed hypocellular marrow with morphologically blastoid cells. A surface marker study revealed the presence of a single clone that was positive for CD7, CD33, CD34, and HLA-DR. A diagnosis of hypoplastic leukemia was made on the basis of morphology and the surface marker studies. Retrospectively, the laboratory findings were the same as those seen at the onset of the disease. The patient did not respond to combination chemotherapy consisting of vincristine, prednisolone, cyclophosphamide, L-asparaginase, and doxorubicin, but administration of etoposide resulted in complete remission. An in vitro study revealed that >95% of the leukemic cells of this patient could be lysed after an incubation with antithymocyte globulin and human AB serum or baby rabbit serum. These findings suggest the efficacy of antithymocyte globulin in treating certain hypoplastic leukemias.

Adolescent↗

PubMed1998

Biologic activity of interleukin 1 (IL-1) alpha in patients with refractory malignancies.

Interleukin 1 alpha (IL-1 alpha) is a cytokine with pleiotropic effects, including cytotoxic-cytostatic activity against some tumor cell lines. We have conducted a phase I study of recombinant human IL-1 alpha (rhIL-1 alpha) in 17 patients with refractory malignancies to examine its toxicity and biologic activity. rhIL-1 alpha was given as a 2-h IV infusion daily for 5 days at five dose levels (0.08, 0.2, 0.8, 2.0, and 5.0 micrograms/m2). Seventeen patients with malignancies were treated, with no objective tumor responses noted. Common toxicities included: fever (100%), rigors and/or chills (96%), myalgia (54%), and headache (48%). Three patients developed grade III hypotension. The maximum tolerated dose was 2.0 micrograms/m2. rhIL-1 alpha induced a significant increase in absolute neutrophil count over baseline (p < 0.05), a delayed but significant increase in platelet count over baseline (p < 0.05), and there was a marked increase in the number of progenitors [colony-forming units (CFU)-G, CFU-M, CFU-GM, CFU-GEMM and burst-forming units (BFU-E)] observed in the peripheral blood. Nine of 12 evaluable patients showed an increase in bone marrow cellularity or myeloid:erthyroid ratio. Immunophenotyping did not demonstrate an increase in peripheral blood or bone marrow CD34+ cells. Interferon-gamma-mediated monocyte cytotoxicity (MCCTX) was significantly enhanced from baseline (p < 0.001), although an increase in direct MCCTX did not reach statistical significance. In summary, rhIL-1 alpha administration is well tolerated at a dose of 2.0 micrograms/m2 with fever, rigors, myalgia, and headache being the most frequent toxicities. Although there were no objective tumor responses, we have demonstrated significant biologic activity with increased neutrophil and platelet counts, increased peripheral blood progenitor cells, and enhanced interferon-gamma-mediated MCCTX.

Adult↗

PubMed2003

Utility of thick smears of bone marrow aspirate in pyrexia of unknown origin.

OBJECTIVE: To determine the diagnostic efficacy of Giemsa stained thick smear of bone marrow aspirate for evidence of malaria in febrile individuals in whom the diagnosis was otherwise unknown. DESIGN: Descriptive case-series study. PLACE AND DURATION OF STUDY: This study was conducted at the Department of Medicine, Sandeman Provincial Hospital, Quetta, in the Balochistan province of Pakistan, between January 1994 and December 1998. SUBJECTS AND METHODS: A total of 80 patients were included in the study, who presented with history of fever for more than 3 weeks with splenomegaly and pancytopenia. The bone marrow specimens of all these patients were examined. The bone marrow was aspirated from the posterior superior iliac spine. Three sets of smears were made. One set of thin smears was stained by Leishman's stain after air-drying and the second set of thin smears was air-dried, fixed with 97% methanol and later stained with 5% Giemsa stain. The third set of smears was a thick smear stained unfixed with 5% Giemsa stain. A temperature of 37 degrees C and a pH of 7.2 was maintained during the staining process. The presence of malarial parasite in the bone marrow was determined. Besides, the degree of megaloblastic change in erythroid series and the bone marrow cellularity were evaluated. The results obtained were recorded and statistically analyzed. RESULTS: Of the 80 bone marrows examined, 32(40%) showed the presence of malarial parasites, 19(23.75%) showed haematological malignancies, 16(20%) showed bone marrow suppression while 12(15%) showed megaloblastic changes. One (1.25%) case showed Leishman-Donovan bodies. Out of 32 cases showing the presence of malarial parasite in bone marrow, only 5(15.6%) revealed parasites, i.e. Plasmodium falciparum gametocytes on thin smear while 32(100%) cases showed Plasmodium falciparum trophozoites and gametocytes on thick smear. The ratio was 1:6.4. These 32 patients were divided into two groups, one group having mild anaemia (>8 g/dL) and the other severe anaemia (Hb<8 g/dL). In this study 20 patients had mild and 12 had severe anaemia. Megaloblastic changes were seen in 15 cases. Hypocellularity was seen in 3 patients with falciparum malaria while 28 showed normocellularity. The marrow was hypercellular in one patient. CONCLUSION: In patients presenting with prolonged fever, splenomegaly and pancytopenia, the Giemsa stained thick smear of bone marrow aspirates for evidence of malarial parasites was far superior to thin smear in diagnosing Plasmodium falciparum malaria.

Adult↗

PubMed1980

Factor V deficiency in Philadelphia-positive chronic myelogenous leukemia.

Factor V deficiency has been identified in 8 of 8 patients 7--20 yr of age, with Philadelphia-positive (Ph1+) chronic myelogenous leukemia (CML). In these 8 patients, factor V deficiency was not due to hepatic dysfunction, factor V inhibitors, or disseminated intravascular coagulation. In 3 patients, factor V activity rose 10%--12% (0.10--0.12 U/ml) after the infusion of 28--31 ml/kg body weight of fresh frozen plasma (FFP). The rise persisted less than 14 hr. The mean measured postinfusion rise in factor V was 18% of the expected rise calculated from the volume of FFP infused in the patients' plasma volume. In 4 patients, a small transient rise in factor V activity occurred after splenectomy or plateletpheresis. Factor V deficiency was completely corrected after a marked reduction in bone marrow cellularity in 2 patients with Ph1+ CML treated with extensive chemotherapy, total body irradiation, and bone marrow transplantation. Factor V deficiency was retrospectively observed in 6 of 20 patients, ages 20--80 yr, with Ph1+ CML and 3 of 6 patients with other myeloproliferative disorders. The factor V deficiency appears to be associated with the large myeloid-megakaryocytic cell mass characteristic of CML and other myeloproliferative disorders.

Adolescent↗

PubMed1992

A trial of recombinant human interleukin-1 in patients with severe refractory aplastic anaemia.

We report here the effects of in vivo administration of recombinant interleukin-1 alpha (rIL-1 alpha) to patients with severe, idiopathic aplastic anaemia. Four patients who were refractory to immunosuppressive therapy and were not bone marrow transplantation candidates received daily doses of 0.03 microgram/kg and 0.10 microgram/kg intravenously as 5 d courses. No significant changes in either peripheral blood counts or bone marrow cellularity were observed at either dose during or following therapy. Two patients showed increased numbers of bone marrow progenitor colonies. Lymphocyte phenotyping demonstrated an elevated percentage of CD8+/DR+ activated suppressor T lymphocytes prior to therapy. After rIL-1 alpha administration, the percentage of CD8+/DR+ cells was reduced or returned to normal in all patients. Significant side-effects included fever, rigours, fatigue, headache and nausea. Transient hypotension was observed at both doses in all patients. These results suggest that while rIL-1 alpha can be safely administered, no significant haematologic improvement was observed in patients with severe aplastic anaemia.

Adolescent↗

PubMed1989

Bone marrow disorders: characterization with quantitative MR imaging.

Thirty patients with various hematologic disorders and 15 healthy control subjects underwent quantitative magnetic resonance (MR) imaging of the lumbar spine with spin-echo techniques. Images of patients with infiltrative bone marrow disorders showed significantly more prolonged T1 times than those of control subjects (P less than .001). It was not possible to distinguish different diffuse infiltrative bone marrow disorders on the basis of T1 values. Aplastic anemia could be distinguished from normality because of significantly shortened T1 (P less than .001). A significant correlation was seen between T1 and bone marrow cellularity (r = .74, P less than .001). T2 was of no value in the characterization of bone marrow disorders. Quantitative MR imaging dose not improve the diagnostic potential of bone marrow imaging in the detection of diffuse marrow infiltrates.

Adult↗

PubMed1975

Direct effects of thyroid hormones on bone marrow erythroid cells of rats.

A stimulatory effect on bone marrow cellularity was observed in normal and nephrectomized rats continuously infused with T3 and T4. Results of bone marrow studies are expressed in absolute numbers of total nucleated erythroid cells per milligram of femoral marrow at the beginning and after 8 hr of continuous intravenous infusions. Administration of T3 and T4 to nephrectomized rats produced a marked and significant increase in total erythroid cells counted. After differential analyses of the nucleated erythroid elements, a significant increase in all erythroid cell types was also observed. Similar results were seen in a control group of rats in which both ureters have been previously ligated and in groups of nephrectomized rats receiving rabbit antiserum against erythropoietin before starting the intravenous infusions of T3 and T4. These results indicate that stimulation of marrow erythropoiesis produced by thyroid hormones in our system is not dependent on renal or extra-renal production of erythropoietin. The progressive introduction of T3 and T4 into the circulation of rats with bilateral nephrectomy or ureter-ligated normal rats, may overload the mechanism of transport of these hormones in plasma. As a consequence, a progressive increase in free active forms of T3 and T4 in plasma may occur. Our interpretation of the present findings is that thyroid hormones stimulate directly bone marrow erythropoiesis. This stimulation is clearly evident when high levels of free active forms of thyroid hormones are present in plasma.

Animals↗

PubMed1994

[Parvovirus B19-induced aplastic crisis in a patient with iron deficiency anemia].

A 38-year-old female was referred to Takaoka City Hospital for treatment of common-cold-like symptom and an episode of transient unconsciousness. Physical examination on admission revealed severe anemia and an ejection heart murmur. Complete blood count revealed microcytic hypochromic anemia (Hb 4.1 g/dl), leukocytopenia (2.600/microliters), thrombocytopenia (7.1 x 10(4)/microliters) and reticulocytopenia (17,000/microliters). The bone marrow cellularity was within normal limits. Cells in the erythroid series were decreased to 5% of total bone marrow nucleated cells with maturation arrest at the level of proerythroblasts. Giant proerythroblasts were observed in 0.2% of marrow nucleated cells. No stainable iron was seen. Both anti-parvovirus B19 IgM antibody and IgG antibody were positive in the serum and parvovirus B19 DNA was detected in the bone marrow cells by polymerase chain reaction. From these results, iron deficiency anemia complicated with pure red cell aplasia secondary to parvovirus B19-induced infection was diagnosed. The anemia gradually improved with administration of sodium ferrous citrate one month after admission. Parvovirus B19 has been reported to cause an aplastic crisis in the patients who has a rapid red cell turn over such as hemolytic anemia or acute blood loss. This report suggested that severe aplastic crisis is also induced in patients with iron deficiency anemia by parvovirus B19-induced infection and warns that careful observation is necessary for the follow up of patients with iron deficiency anemia.

Adult↗

PubMed1999

Prolactin exerts hematopoietic growth-promoting effects in vivo and partially counteracts myelosuppression by azidothymidine.

Prolactin (PRL) is a neuroendocrine hormone that influences immune and hematopoietic development. The mechanism of action of this hormone in vivo remains unclear; therefore, we assessed the effects of PRL on hematopoiesis in vivo and in vitro. Normal resting mice were treated with 0, 1, 10, or 100 microg of recombinant human prolactin (rhPRL) for 4 consecutive days and euthanized on the fifth day for analysis of myeloid and erythroid progenitors in the bone marrow and spleen. Both frequencies and absolute numbers of splenic colony-forming unit granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-e) were significantly increased in mice receiving rhPRL compared to the controls that had received saline only. Bone marrow cellularities were not significantly affected by any dose of rhPRL, but the absolute numbers and frequencies of bone marrow CFU-GM and BFU-e were augmented by rhPRL. These results suggest that rhPRL can promote hematopoiesis in vivo. Because rhPRL augments myeloid development in vivo, we examined the potential of the hormone to reverse the anemia and myelosuppression induced by azidothymidine (AZT). Mice were given rhPRL injections concurrent with 2.5 mg/mL AZT in drinking water. rhPRL partially restored hematocrits in the animals after 2 weeks of treatment and increased CFU-GM and BFU-e in both spleens and bone marrow. The experiments with AZT and rhPRL support the conclusion that the hormone increases myeloid and erythroid progenitor numbers in vivo, and they suggest that the hormone is clinically useful in reversing myelosuppression induced by AZT or other myeloablative therapies.

Animals↗

PubMed2004

Impaired bone marrow hematopoietic progenitor cell function in rheumatoid arthritis patients candidated to autologous hematopoietic stem cell transplantation.

We have evaluated bone marrow morphology, percentage of bone marrow CD34(+) cells, proliferative activity of bone marrow precursors, clonogenic assay (BFU-E and CFU-GM) in short-term bone marrow cultures, and bone marrow cell apoptosis, together with serum TNF-alpha and IL-6, in 16 chronic, refractory RA patients, as well as in five healthy controls. Of 16 RA patients (68.7%), 11 showed a reduced bone marrow cellularity, while it was normal in all the controls. In RA patients, the median percentage of CD34(+) bone marrow cells, the median percentage of proliferating bone marrow myeloid precursors, and the median number of both BFU-E and CFU-GM colonies were significantly lower than observed in the controls. As far as TNF-alpha and IL-6 titers is concerned, the latter did not significantly differ from controls' values, while TNF-alpha titers were significantly lower in healthy controls. Finally, the median apoptotic index of early bone marrow myeloid cells of RA patients was significantly higher compared with controls. These observations may identify the biological risk factors for impaired mobilization and/or engraftment when RA patients are candidates for autologous hematopoietic stem cell grafting.

Adult↗

PubMed1980

Enhancement of hemopoietic recovery after bone marrow transplantation with the addition of nucleated blood cells in mice.

Recovery of bone marrow cellularity, CFU-C, and CFU-S were studied sequentially over 90 days time after syngeneic bone marrow transplantation in mice. A minimal cell dose of 2 X 10(5) bone marrow cells was given. At day 28 after transplantation, CFU-C reached more than 50% of the normal range whereas the CFU-S concentration was less than 15%. Normalization of CFU-S occurred at day 90. The effect of the addition of peripheral blood nucleated cells on bone marrow hemopoietic recovery was studied at day 28. The augmentation of CFU-C and CFU-S recoverey were dose dependent. Optimal enhancement was seen with bone marrow to blood ratios of 1:1 and 1:2.5. This enhancement effect was lost when nucleated blood cells in a ratio of 1:10 were administered.

Animals↗

PubMed2003

Akt signaling regulates side population cell phenotype via Bcrp1 translocation.

Akt is an important regulator of cell survival, growth, and glucose metabolism in many cell types, but the role of this signaling molecule in hematopoietic stem cells is poorly defined. Side population (SP) cells are enriched for hematopoietic stem cell activity and are defined by their ability to efficiently efflux Hoechst 33342. Bone marrow from Akt1-null mice exhibited a reduced SP fraction. However, bone marrow cellularity, growth factor-responsive progenitor cultures, and engraftable stem cells were normal in these mice. Treatment of bone marrow with LY294002, an inhibitor of the Akt effector protein phosphatidylinositol 3-kinase, led to a reversible loss of the SP fraction. Bcrp1, which encodes the Hoechst dye transporter, was translocated from the membrane to the intracellular compartment under conditions that promote the SP-depleted state. Lentivirus-mediated overexpression of Akt1 in bone marrow markedly increased the SP fraction, whereas there was no effect on bone marrow from Bcrp(-/-) mice. These data suggest that Akt signaling modulates the SP cell phenotype by regulating the expression of Bcrp1.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed1995

DNA adduct formation in the bone marrow of B6C3F1 mice treated with benzene.

We used P1-enhanced 32P-postlabeling to investigate DNA adduct formation in the bone marrow of B6C3F1 mice treated intraperitoneally with benzene (BZ). No adducts were detected in the bone marrow of controls or mice treated with various doses of BZ once a day. After twice-daily treatment with BZ, 440 mg/kg, for 1 to 7 days, one major and two minor DNA adducts were detected. The relative adduct levels ranged from 0.06-1.46 x 10(-7). In vitro treatment of bone marrow from B6C3F1 mice with various doses of hydroquinone (HQ) for 24 h also produced three DNA adducts. These adducts were the same as those formed after in vivo treatment of bone marrow with BZ. Co-chromatography experiments indicated that the principal DNA adduct detected in the bone marrow of B6C3F1 mice was the same as that detected in HL-60 cells treated with HQ. This finding suggests that HQ may be the principal metabolite of BZ leading to DNA adduct formation in vivo. DNA adduct 2 corresponds to the DNA adduct formed in HL-60 cells treated with 1,2,4-benzenetriol. DNA adduct 3 remains unidentified. After a 7-day treatment with BZ, 440 mg/kg twice a day, the number of cells per femur decreased from 1.6 x 10(7) to 0.85 x 10(7), indicating myelotoxicity. In contrast, administration of BZ once a day produced only a small decrease in bone marrow cellularity. These studies demonstrate that metabolic activation of BZ leads to the formation of DNA adducts in the bone marrow. Further investigation is required to determine the role of DNA adducts and other forms of DNA damage in the myelotoxic effects of exposure to BZ.

Animals↗

PubMed2003

Periodic oscillation of blood leukocytes, platelets, and hemoglobin in a patient with chronic eosinophilic leukemia.

Chronic eosinophilic leukemia (CEL) is a rare myeloproliferative disease in which autonomous, clonal proliferation of eosinophilic precursors results in persistent increase of eosinophils in the blood and bone marrow. A case of CEL spontaneous oscillation of white blood cell (WBC) count is presented. The cycle of WBC variation comprised about 60 days. Similar cyclic variations were noted in his platelet count, hemoglobin level and bone marrow cellularity, as well as in the spleen size, which was directly correlated with the WBC count. The numbers of bone marrow erythroid colony-forming units (CFU-E), granulocyte-macrophage colony-forming units (CFU-GM) and the serum level of colony-stimulating factors (CSFs) were also regularly changed during the oscillation of WBC. Bone marrow hyperplasia was accompanied with the increase in peripheral WBC count, suggesting that the variation of cell production caused the cyclic oscillation.

Bone Marrow↗

PubMed1995

Regulatory role of osteogenic growth peptide in proliferation, osteogenesis, and hemopoiesis.

Bone marrow regeneration after injury is preceded by local and systemic osteogenic reactions. Recently, an osteogenic growth peptide was characterized in the regenerating marrow. The osteogenic growth peptide also is abundant in normal serum where it is markedly and transiently increased after marrow injury. This increase and the osteogenic growth peptide-induced stimulation of bone formation in vivo suggest a role for this peptide in mediating the systemic osteogenic response. In vitro, the osteogenic growth peptide is an autocrine mitogen for osteoblastic and fibroblastic cells. It also stimulates alkaline phosphatase activity and matrix mineralization. The serum osteogenic growth peptide is downregulated in osteoporotic ovariectomized mice. The osteogenic growth peptide levels as well as the bone loss, tetracycline uptake, and serum osteocalcin are reversed by exogenously administered osteogenic growth peptide. In normal mice, the osteogenic growth peptide increases white blood cell counts and total femoral bone marrow cellularity. These increases include all the hemopoietic lineages. When given to mice for 1 week before ablative radiotherapy and bone marrow transplantation, synthetic osteogenic growth peptide stimulates the bone marrow transplant engraftment; optimal osteogenic growth peptide doses doubled the survival rate. These data indicate that osteogenic growth peptide has an important role in the pathogenesis and treatment of systemic bone loss and provide a basis for further development of an antiosteoporotic osteogenic growth peptide therapy. It is suggested also that the osteogenic growth peptide promotes hemopoiesis secondary to the stimulation of the stromal (particularly osseous) microenvironment.

Animals↗

PubMed1999

Marrow engraftment of hematopoietic stem and progenitor cells is independent of Galphai-coupled chemokine receptors.

The mechanism of hematopoietic stem and progenitor cell (HSPC) homing to hematopoietic organs after transplantation is still poorly understood. There is evidence that HSPC homing is a multistep process involving integrins and other adhesion molecules as well as stimulation of cytokine and chemokine receptors, similar to the process of lymphocyte recirculation and leukocyte emigration. This study examined the effect of pertussis toxin (PT), an inhibitor of signaling by many Galphai protein-coupled chemokine receptors, on engraftment of HSPC. An in vitro incubation of total bone marrow cells in PT-supplemented media prior to transplantation into lethally irradiated syngeneic mice resulted in an increase in marrow repopulation and a parallel decrease of colony-forming unit-spleen (CFU-S) on day 13. PT treatment of Rh(low)Lineage(neg)Sca-1pos cells prior to transplant resulted in delayed spleen cell engraftment, but no observable difference in the bone marrow cellularity compared to animals transplanted with untreated cells. FACS analysis of hematopoietic organs revealed that myeloid cell recovery in the bone marrow was unaffected by PT treatment of HSPC. However, a reduced myeloid cell recovery in the spleen and an increased B lymphoid recovery in both the spleen and the bone marrow were observed in recipients of PT-treated grafts relative to untreated grafts. To test the hypothesis that PT inhibits proliferation rather than engraftment of HSPC in the spleen, the effect of PT on cytokine-stimulated proliferation of HSPC was tested. Although an inhibition of the growth of microcolonies in response to interleukin 6 as a single cytokine could be observed after PT treatment, colony growth of HSPC after steel factor or steel factor + interleukin 6 stimulation was unaffected by PT. This study demonstrates that bone marrow, but not splenic, recovery after HSPC transplantation is independent of PT-sensitive mechanisms. It is likely that PT inhibits spleen cell recovery by disrupting a Galphai-coupled homing receptor expressed by HSPC. These studies support the hypothesis that distinct mechanisms regulate splenic vs bone marrow engraftment of HSPC, and that B lymphocyte progenitors and HSPC can utilize a PT-resistant homing mechanism to localize in hematopoietic tissues after transplantation.

Animals↗