scholarly journals Autoradiographic Study on the Origin and Fate of Small Lymphoid Cells in the Dog Bone Marrow: Effect of Femoral Artery Clamping during in Vivo Availability of H3-Thymidine

Blood ◽  
1964 ◽  
Vol 24 (3) ◽  
pp. 254-266 ◽  
Author(s):  
G. KEISER ◽  
H. COTTIER ◽  
N. ODARTCHENKO ◽  
V. P. BOND
Keyword(s):  
Bone Marrow ◽  
Femoral Artery ◽  
Blood Stream ◽  
Autoradiographic Study ◽  
Precursor Cells ◽  
Lymphoid Cells ◽  
The Other ◽  
Dog Bone ◽  
Two Populations

Abstract The origin and fate of small lymphoid cells in the dog bone marrow were studied autoradiographically by observing the effect of clamping of the femoral artery during in vivo availability of H3-thymidine. Heavily labeled small lymphoid cells appeared in the bone marrow of the clamped leg 3 hours after injection of the tracer and increased in number up to 6 days. The labeling indices of these cells, however, were significantly lower than those of control marrow. A possible interpretation is that dog bone marrow contains two populations of small lymphoid cells, one migrating into the marrow via the blood stream, the other originating from local precursor cells within the marrow. There was no evidence for a transformation of migrated small lymphoid cells into erythroblasts during the first 48 hours after injection of H3-thymidine.

scholarly journals Distribution of mast-cell precursors in hematopoeitic and lymphopoietic tissues of mice.

1979 ◽  
Vol 150 (3) ◽  
pp. 482-490 ◽  
Author(s):  
Y Kitamura ◽  
M Shimada ◽  
S Go ◽  
H Matsuda ◽  
K Hatanaka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Bone Marrow Cells ◽  
Cell Number ◽  
Precursor Cells ◽  
Lymphoid Cells ◽  
Experimental Systems ◽  
Chediak Higashi Syndrome

Two experimental systems were used to investigate the origin of precursor cells which differentiate into tissue mast cells in vivo. (a) Increase of mast cell number was examined in the skin, stomach, cecum, and mesentery of genetically mast cell-depleted WBB6F1 (WB X C57BL/6)-W/WV mice after the injection of various hematolymphoid cells of congenic +/+ mice. (b) Appearance of mast cells with giant granules was studied in irradiated C57BL/6-+/+ mice after the injection of lymphoid cells of C57BL/6-bgJ/bgJ (beige, Chediak-Higashi syndrome) mice. Concentrations of mast cell precursors in the thymus, lymph node and Peyer's patch were less than 0.1% of the concentration in the bone marrow. Neither treatment of donor bone marrow cells with anti-Thy-1.2 serum and complement nor thymectomy of the recipient mice affects the development of mast cells in the skin, stomach, cecum, and mesentery. Moreover, the number of mast cells increased to normal level when the skin of WBB6F1-W/WV mice was grafted on the back of nude athymic (BALB/c-nu/nu) mice. These results indicate that mast cell precursors are derived from hematopoietic tissues rather than lymphopoetic ones and that the differentiation of the precursor cells does not depend on T lymphocytes or the thymus.

scholarly journals Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hideki Ueyama ◽  
Yoichi Ohta ◽  
Yuuki Imai ◽  
Akinobu Suzuki ◽  
Ryo Sugama ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Structure ◽  
Precursor Cells ◽  
The Other ◽  
Bone Morphogenetic Protein 2 ◽  
New Bone Formation ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Left Femur

Abstract Background Bone morphogenetic proteins (BMPs) induce osteogenesis in various environments. However, when BMPs are used alone in the bone marrow environment, the maintenance of new bone formation is difficult owing to vigorous bone resorption. This is because BMPs stimulate the differentiation of not only osteoblast precursor cells but also osteoclast precursor cells. The present study aimed to induce and maintain new bone formation using the topical co-administration of recombinant human BMP-2 (rh-BMP-2) and zoledronate (ZOL) on beta-tricalcium phosphate (β-TCP) composite. Methods β-TCP columns were impregnated with both rh-BMP-2 (30 µg) and ZOL (5 µg), rh-BMP-2 alone, or ZOL alone, and implanted into the left femur canal of New Zealand white rabbits (n = 56). The implanted β-TCP columns were harvested and evaluated at 3 and 6 weeks after implantation. These harvested β-TCP columns were evaluated radiologically using plane radiograph, and histologically using haematoxylin/eosin (H&E) and Masson’s trichrome (MT) staining. In addition, micro-computed tomography (CT) was performed for qualitative analysis of bone formation in each group (n = 7). Results Tissue sections stained with H&E and MT dyes revealed that new bone formation inside the β-TCP composite was significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Micro-CT data also demonstrated that the bone volume and the bone mineral density inside the β-TCP columns were significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Conclusions The topical co-administration of both rh-BMP-2 and ZOL on β-TCP composite promoted and maintained newly formed bone structure in the bone marrow environment.

scholarly journals Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Femoral Artery ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

scholarly journals In vivo tracking of transplanted macrophages with near infrared fluorescent dye reveals temporal distribution and specific homing in the liver that can be perturbed by clodronate liposomes

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0242488
Author(s):  
Satoshi Nishiwaki ◽  
Shigeki Saito ◽  
Kyosuke Takeshita ◽  
Hidefumi Kato ◽  
Ryuzo Ueda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Normal State ◽  
Near Infrared ◽  
Temporal Distribution ◽  
Organ Damage ◽  
The Other ◽  
Acquired Immunity ◽  
Activated Macrophages ◽  
Clodronate Liposomes

Macrophages play an indispensable role in both innate and acquired immunity, while the persistence of activated macrophages can sometimes be harmful to the host, resulting in multi-organ damage. Macrophages develop from monocytes in the circulation. However, little is known about the organ affinity of macrophages in the normal state. Using in vivo imaging with XenoLight DiR®, we observed that macrophages showed strong affinity for the liver, spleen and lung, and weak affinity for the gut and bone marrow, but little or no affinity for the kidney and skin. We also found that administered macrophages were still alive 168 hours after injection. On the other hand, treatment with clodronate liposomes, which are readily taken up by macrophages via phagocytosis, strongly reduced the number of macrophages in the liver, spleen and lung.

scholarly journals Radioautographic Studies of Bone Marrow Lymphocytes in Vivo and in Diffusion Chamber Cultures

Blood ◽  
1964 ◽  
Vol 23 (1) ◽  
pp. 1-17 ◽  
Author(s):  
D. G. OSMOND ◽  
N. B. EVERETT
Keyword(s):  
Bone Marrow ◽  
Large Scale ◽  
Bone Marrow Cells ◽  
Tritiated Thymidine ◽  
Diffusion Chamber ◽  
Blood Stream ◽  
Turnover Time ◽  
Diffusion Chambers ◽  
Transitional Cells

Abstract Radioautography with tritiated thymidine has been utilized to examine the turnover rate and origin of small lymphocytes in the bone marrow of the guinea-pig. Very few marrow lymphocytes were initially labeled by a single injection of tritiated thymidine, but thereafter the number of labeled lymphocytes rapidly increased to high maximum levels at 3 days. Analysis of the labeling curves and grain counts indicates that the population of marrow lymphocytes is maintained in a dynamic steady state with an average turnover time of 3 days or less. Suspensions of bone marrow cells were isolated from the circulation within intraperitoneal diffusion chambers after short-term labeling with tritiated thymidine in vivo. Although very few small lymphocytes were labeled when introduced into the diffusion chambers, a considerable percentage became labeled during the subsequent culture period. Tritiated thymidine was also administered intravenously whilst excluded from one hind limb by the application of an occlusive compression bandage for 20 minutes. Very few labeled small lymphocytes were found after 72 hours in the tibial marrow of the initially occluded limb, whereas the normal high percentage was labeled in the control tibial marrow. These experiments do not demonstrate any large-scale influx of small lymphocytes from the blood stream into the marrow parenchyma. They suggest that newly formed small lymphocytes appear in the marrow as a result of the division of locally situated precursor cells, but the mechanism of intramedullary lymphocytopoiesis is uncertain. "Transitional" cells, intermediate in morphology between blast cells and small lymphocytes, synthesize DNA and are actively proliferative, but they do not appear to account fully for the rate of lymphocyte production. Certain large, undifferentiated labeled cells appeared in the bone marrow as a result of hematogenous migration. Some implications of these findings are discussed.

Most of the Short Term Repopulating Cells in Human Mobilized Peripheral Blood Do Not Have a Side Population (SP) Phenotype.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2867-2867
Author(s):  
M. Fischer ◽  
M. Schmidt ◽  
S. Klingenberg ◽  
C. Eaves ◽  
C. von Kalle4 ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Side Population ◽  
Isolation Procedure ◽  
Lymphoid Cells ◽  
Short Term ◽  
Hoechst 33342 ◽  
Hoechst Staining ◽  
Mobilized Peripheral Blood

Abstract The multidrug resistance transporter, ABCG2, is expressed in primitive hematopoietic stem cells from a variety of sources. These cells are detected in dual wave-length fluorescent FACS profiles as a “side population” (SP cells) on the basis of their ability to efflux the fluorescent dye, Hoechst 33342. We have previously shown that 2 types of human short term repopulating cells (STRC) can be enumerated by limiting dilution analysis of their efficient ability to regenerate exclusively myeloid cells after 3 weeks (STRC-Ms), or both myeloid and lymphoid cells after 6–12 weeks (STRC-MLs) in NOD/SCID-b2microglobulin-/- (b2m-/-) mice. Previous findings also implicated these STRCs as determinants of the rapidity of early hematologic recovery in patients transplanted with cultured mobilized peripheral blood (mPB) cells. Here we asked whether any human STRCs have an SP phenotype and hence whether the isolation of SP cells would retain the rapid repopulating activity of a clinical transplant. CD3- SP and non-SP cells were isolated by FACS from low-density (LD) mPB cells after Hoechst staining and transplanted at limiting dilutions into 117 sublethally irradiated b2m-/- mice. The numbers and types of human hematopoietic cells present in the bone marrow of these mice were subsequently monitored by FACS analysis of bone marrow cells aspirated serially, 3, 8 and 12 wks post-transplant. A verapamil-sensitive SP population was reproducibly detected in all 5 patients’ samples studied (0.039 ± 0.012% of the CD3- LD cells). The in vivo assays failed to detect either STRC-Ms or STRC-MLs in the SP fraction and all these activities were obtained from the non-SP cells. If even a single recipient of the largest dose of SP cells transplanted had been positive, this would have detected 10% of the STRCs present. Thus, &gt;90% of all STRC-M and STRC-ML in mPB are non-SP cells. However, 4 of 40 mice transplanted with SP mPB cells produced some B-lymphoid cells only starting 12 wks post-transplant. However, this result is difficult to interpret since subjecting the STRC-Ms to the Hoechst 33342 staining and FACS isolation procedure alone eliminated their ability to generate megakaryocytic progeny in vivo, although this did not occur when these cells were just stained for CD34 and then isolated by FACS. In addition, the differentiation behaviour of STRC-MLs was not affected by the Hoechst staining and subsequent FACS isolation procedure. In summary, we demonstrate that purification of SP cells depletes human mPB transplants of STRCs, thereby raising serious concerns about the safety of any clinical use of SP cell-enriched transplants as stem cell support after myeloablation. Our results also suggest that the staining and enrichment procedure for isolating SP human cells may differentially affect the lineage potential of some types of STRCs, including those whose activity may be indispensable for rapid and multi-lineage hematologic recovery.

Mesenchymal Stem Cells From Patients with Acute Myeloid Leukemia (AML) Can Differentiate Into B-Cells in NOD/SCID/IL-2Rγ-/- Mice.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4573-4573
Author(s):  
Rui-Yu Wang ◽  
Yue-Xi Shi ◽  
Zhihong Zeng ◽  
Wendy D. Schober ◽  
Teresa J. McQueen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
B Lymphocyte ◽  
Conflicts Of Interest ◽  
Lymphoid Cells ◽  
Proliferative Potential ◽  
Unexpected Finding ◽  
Nog Mice

Abstract Abstract 4573 Human mesenchymal stem cells (MSCs) derived from bone marrows are characterized by high proliferative potential and pluripotentiality to differentiate into multiple lineages such as osteo-, chondro-, and adipogenic cells. MSC express CD105, CD73 and CD90, but not CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. In this study, we observed that MSC derived from the bone marrow of four AML patients differentiated into B-cell lymphoblasts with NOD/SCID/IL-2Rg-/- engraftment potential. MSC cell lines were established by culturing adherent cells from newly diagnosed AML (n=4) age 20 to 74 years in alpha-DMEM medium supplement with 20% fetal bovine serum. Surface antigen phenotype analysis and G-banding karyotype analysis were performed in passage 2 to 4. FACS-sorted CD90 positive cells were then intravenously (I.V.) injected into NOD/SCID/IL-2Rg-/- (NOG) mice via tail vein (n=9) or into the bone marrow (n=3). Circulating cells were analyzed for CD19, CD33, CD34, and CD90 expression on day 36, 45, 60, 75 after injection of MSC. Results 1) G-banding showed normal karyotype in all MSC; 2) Injected MSC engrafted and differentiated in NOG mice. Surprisingly, CD19 positive cells were found in all samples starting on day 36 (table) and increased on day 60 and 75 (from d36: 6.9±3.5%, d45:0.7±0.1%, d60:2.6 ± 1.6% and d75: 9.3 ± 1.0%); 3) CD90 positive cells were found on day 45 (range from 0.07-3.96% and decreased to 0.1-0.5% on day 75). Low percentage of CD33 (day 45: 0.19-0.78% and day 60: 0.12-2.53%) and CD34 positive cells (day 45: 0.32-1.9% and day 60: 0.21-2.39%) were observed before day 60 and were undetectable by day 75. Table shows the percentages of CD19+ cells found in circulation in NOD/SCID/IL-2Rg-/- (NOG) mice after MSC I.V. or intra-bone marrow injection. (* Mice died after phlebotomy.) Conclusion Human MSC derived from AML bone marrows have the capacity to differentiate into CD19 positive B lymphocyte in NOG mice in vivo. It has previously been reported that AML can be propagated by a leukemic stem cell with lymphoid characteristics (Cancer Cell 2006, 10, 363-74). Data reported here suggest the possibility that AML-derived MSC give rise to lymphoid cells that engraft in NOG mice. This unexpected finding could shed light on the role of stroma cells in the pathogenesis and propagation of leukemias. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Highly restricted expression of a stromal cell determinant in mouse bone marrow in vivo.

1992 ◽  
Vol 176 (4) ◽  
pp. 927-935 ◽  
Author(s):  
K Jacobsen ◽  
K Miyake ◽  
P W Kincade ◽  
D G Osmond
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Plasma Membranes ◽  
Cell Clone ◽  
Close Association ◽  
Lymphoid Cells ◽  
Mouse Bone Marrow ◽  
Hemopoietic Cells

B lymphocyte precursor cells in mouse bone marrow develop in close association with stromal cells which provide essential growth signals. To identify molecules that may normally play a role in this interaction we have examined the in vivo binding of a new monoclonal antibody (mAb) (KMI6) that recognizes a determinant on a bone marrow stromal cell line (BMS2) in vitro. Flow cytometric and radioautographic evaluations revealed that the antigen recognized by KMI6 is represented on the surface of an extremely small number of cells in bone marrow cell suspensions from adult mice. An apparent molecular mass of 110 kD was obtained by surface labeling of a stromal cell clone and immunoprecipitation. Purified mAb KMI6 labeled with 125I was then given intravenously to young C3H/HeJ mice. Unbound mAb was washed out by cardiac perfusion and femoral bone marrow was examined by light and electron microscope radioautography. KMI6 labeling was heavy on the plasma membrane of many stromal cells, especially those located towards the outer subosteal region. The KMI6-labeled stromal cells were usually associated with cells of lymphoid morphology which they often completely surrounded. The labeling was restricted to areas of stromal cell plasma membranes in contact with lymphoid cells. The lymphoid cells themselves, as well as macrophages and other hemopoietic cells, failed to bind mAb KMI6 significantly. Stromal cells in bone marrow depleted of hemopoietic cells by gamma-irradiation (9,5 Gy) bound mAb KMI6 at reduced intensity. The results demonstrate that the KMI6 determinant, a 110-kD protein, is expressed on bone marrow stromal cells in vivo. Its restriction to areas of interaction with lymphoid cells suggests a role in forming microenvironmental niches of B lymphopoiesis. The surface membrane of individual stromal cells may thus be functionally polarized towards interacting B cell precursors and other hemopoietic cells.

scholarly journals Graft-host tolerance in bone marrow transplant chimeras. Absence of graft-versus-host disease is associated with unresponsiveness to minor histocompatibility antigens expressed by all tissues

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3221-3228
Author(s):  
S Brochu ◽  
C Baron ◽  
R Belanger ◽  
C Perreault
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Lymphocytes ◽  
Marrow Transplant ◽  
Lymphoid Cells ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens ◽  
Cd8 Cells ◽  
B10 Cells

Because bone marrow (BM) transplantation is used with increasing frequency, it is important to elucidate the mechanisms involved in the establishment of tolerance to host minor histocompatibility antigens (MiHA) in recipients transplanted with T-cell-undepleted marrow grafts. We have previously shown that BM chimeras transplanted across MiHA barriers showed specific unresponsiveness to MiHA expressed on recipient-type concanavalin A blasts. Because expression of many MiHA is tissue-specific, we wanted to determine if chimera T lymphocytes would be tolerant to MiHA expressed by all host tissues and organs. To investigate this issue, we measured in vivo proliferation of lymphoid cells from normal C57BL/10 (B10) mice and (B10-->LP) chimeras in tissues and organs of lethally irradiated syngeneic and allogeneic recipients. Donor B10 cells were either untreated, or depleted with anti-Thy-1.2, anti-CD4, or anti-CD8 antibodies. Transplantation of B10 cells in LP recipients triggered an important T-cell-dependent 125I- dUrd uptake in several organs that involved both CD4+ and CD8+ cells. Using Thy-1-congeneic mice we showed that in long-term chimeras practically all CD4+ and CD8+ T lymphocytes were derived from hematopoietic progenitors and not from mature T cells present in the BM graft. When (B10-->LP) BM chimera cells were injected to secondary recipients, no proliferation was observed in any organ of LP hosts whereas normal proliferation was seen in H-2k allogeneic hosts. Thus, in these BM chimeras, tolerance encompasses MiHA expressed by all organs.

scholarly journals Severe Combined Immunodeficiency Mice Engrafted With Human T Cells, B Cells, and Myeloid Cells After Transplantation With Human Fetal Bone Marrow or Liver Cells and Implanted With Human Fetal Thymus: A Model for Studying Human Gene Therapy

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1800-1810 ◽  
Author(s):  
Sergey Yurasov ◽  
Tobias R. Kollmann ◽  
Ana Kim ◽  
Christina A. Raker ◽  
Moshe Hachamovitch ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Bone Marrow ◽  
T Cells ◽  
Peripheral Blood ◽  
Severe Combined Immunodeficiency ◽  
Precursor Cells ◽  
Scid Mice ◽  
Combined Immunodeficiency ◽  
Human T Cells

To develop an in vivo model wherein human hematopoiesis occurs, we transplanted severe combined immunodeficiency (SCID) mice with either human fetal bone marrow (HFBM) or human fetal liver (HFL). After transplantation of SCID mice with cultured HFBM (BM-SCID-hu mice) or HFL cells (Liv-SCID-hu mice), significant engraftment of the mouse bone marrow (BM) and population of the peripheral blood with human leukocytes was detected. Human colony-forming unit–granulocyte macrophage and burst forming unit-erythroid were detected in the BM of the BM-SCID-hu and Liv-SCID-hu mice up to 8 months after transplantation. When the HFBM or HFL cells were transduced with a retroviral vector before transplantation, integrated retroviral sequences were detected in human precursor cells present in the SCID mouse BM and in leukocytes circulating in the peripheral blood (PB) up to 7 months after transplantation. The PB of the BM-SCID-hu mice also became populated with human T cells after implantation with human thymic tissue, which provided a human microenvironment wherein human pre-T cells from the BM could mature. When the HFBM was retrovirally transduced before transplantation, integrated retrovirus was detected in sorted CD4+CD8+ double positive and CD4+ single positive cells from the thymic implant and CD4+ cells from the PB. Taken together, these data indicated that the BM of our BM-SCID-hu and Liv-SCID-hu mice became engrafted with retrovirally transduced human hematopoietic precursors that undergo the normal human hematopoietic program and populate the mouse PB with human cells containing integrated retroviral sequences. In addition to being a model for studying in vivo human hematopoiesis, these mice should also prove to be a useful model for investigating in vivo gene therapy using human stem/precursor cells.

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