Proliferative potential of CFUs from bone marrow of thymectomized mice

1992 ◽  
Vol 114 (2) ◽  
pp. 1196-1198
Author(s):  
T. V. Todriya
Keyword(s):  
Bone Marrow ◽  
Proliferative Potential ◽  
Thymectomized Mice

scholarly journals Clinical significance of proliferative potential of occult metastatic cells in bone marrow of patients with breast cancer

2003 ◽  
Vol 89 (3) ◽  
pp. 539-545 ◽  
Author(s):  
J-Y Pierga ◽  
C Bonneton ◽  
H Magdelénat ◽  
A Vincent-Salomon ◽  
C Nos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Clinical Significance ◽  
Proliferative Potential ◽  
Metastatic Cells

Murine pluripotent hematopoietic progenitors constitutively expressing a normal erythropoietin receptor proliferate in response to erythropoietin without preferential erythroid cell differentiation

1994 ◽  
Vol 14 (7) ◽  
pp. 4834-4842
Author(s):  
A Dubart ◽  
F Feger ◽  
C Lacout ◽  
F Goncalves ◽  
W Vainchenker ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Bone Marrow Cells ◽  
Erythropoietin Receptor ◽  
Erythroid Cell ◽  
Major Influence ◽  
Proliferative Potential ◽  
Steel Factor ◽  
Interleukin 3 ◽  
Marrow Cells

Erythropoietin (EPO) is a prime regulator of the growth and differentiation of erythroid blood cells. The EPO receptor (EPO-R) is expressed in late erythroid progenitors (mature BFU-E and CFU-E), and EPO induces proliferation and differentiation of these cells. By introducing, with a retroviral vector, a normal EPO-R cDNA into murine adult bone marrow cells, we showed that EPO is also able to induce proliferation in pluripotent progenitor cells. After 7 days of coculture with virus-producing cells, bone marrow cells were plated in methylcellulose culture in the presence of EPO, interleukin-3, or Steel factor alone or in combination. In the presence of EPO alone, EPO-R virus-infected bone marrow cells gave rise to mixed colonies comprising erythrocytes, granulocytes, macrophages and megakaryocytes. The addition of interleukin-3 or Steel factor to methylcellulose cultures containing EPO did not significantly modify the number of mixed colonies. The cells which generate these mixed colonies have a high proliferative potential as shown by the size and the ability of the mixed colonies to give rise to secondary colonies. Thus, it appears that EPO has the same effect on EPO-R-expressing multipotent cell proliferation as would a combination of several growth factors. Finally, our results demonstrate that inducing pluripotent progenitor cells to proliferate via the EPO signaling pathway has no major influence on their commitment.

scholarly journals Protection of murine bone marrow by dexamethasone during cytotoxic chemotherapy

Blood ◽  
1994 ◽  
Vol 83 (1) ◽  
pp. 65-71 ◽  
Author(s):  
AB Kriegler ◽  
D Bernardo ◽  
SM Verschoor
Keyword(s):  
Bone Marrow ◽  
Protective Effect ◽  
Optimal Dose ◽  
Cytotoxic Chemotherapy ◽  
Proliferative Potential ◽  
Murine Bone Marrow ◽  
Cell Numbers ◽  
Maximum Benefit ◽  
Chemotherapy Agents ◽  
Negative Regulatory Role

Abstract Corticosteroids have the ability to suppress the production of growth factors and cytokines and are thus implicated in the negative regulation of hematopoiesis. We have shown that the corticosteroids, prednisolone and dexamethasone, were able to effectively protect progenitor cells in four strains of mice against cell-cycle-specific antimetabolic chemotherapy agents. The highest levels of protection against 5-fluorouracil (FU; 200 mg/kg) were achieved when two or three intraperitoneal injections of dexamethasone were administered between - 7 and +3 hours at a dose of 7.5 mg/kg/injection (optimal dose) or by continuous infusion between -4 and +20 hours. This protective effect is manifested as an increase in the number of high proliferative potential colony-forming cells that survive in the bone marrow 3 days after treatment with FU from between 0.5% and 11% to between 10% and 34% of normal. The bone marrow progenitors and blood cell numbers return to normal from 3 to 5 days and 1 to 2 days earlier, respectively. Less dexamethasone than prednisolone is required to give an equivalent protective effect, which is consistent with their anti-inflammatory potency. These findings are further evidence of the negative regulatory role played by corticosteroids, and indicate that the treatment schedules of corticosteroids during cancer therapy need to be reexamined to obtain the maximum benefit from their use.

scholarly journals The effect of 5-fluorouracil on erythropoiesis

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1164-1170 ◽  
Author(s):  
IN Rich
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Normal Values ◽  
Biologically Active ◽  
Stem Cell Population ◽  
Enzyme Linked Immunosorbent Assay ◽  
Proliferative Potential ◽  
Colony Forming Unit ◽  
Kinetics Of

Abstract The effects of a single dose (150 mg/kg) of 5-fluorouracil on mature erythroid and erythropoietic and multipotential in vitro precursor populations in the bone marrow and spleen and circulating biologically (erythroid colony forming unit [CFU-E] assay) and immunologically active (enzyme-linked immunosorbent assay) erythropoietin (Epo) are described. All mature erythroid (reticulocytes, erythrocytes) and in vitro erythropoietic precursors (CFU-E, erythroid burst-forming unit [BFU-E]) are severely reduced, if not eradicated. Transient repopulation of the pure BFU-E and CFU-E populations on days 6 and 7, respectively, produces a marked reticulocytosis after day 9. Circulating Epo increases to above normal values by day 2. However, whereas biologically active Epo remains constant at this level until day 9, immunologically active Epo continually increases; by day 12, however, both assays detect circulating Epo levels of about 400 mU/mL. In vitro multipotential stem cells (BFU-E mix) are reduced to 32% on day 1, 7.6% on day 2, and return to normal values between days 4 and 5. The survival and repopulation kinetics of the BFU-E mix imply a stem cell population more mature than the high proliferative potential colony-forming cells. However, the BFU-E mix may be responsible for erythropoiesis repopulating ability.

scholarly journals Long-term generation and expansion of human primitive hematopoietic progenitor cells in vitro

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 661-669 ◽  
Author(s):  
EF Srour ◽  
JE Brandt ◽  
RA Briddell ◽  
S Grigsby ◽  
T Leemhuis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Bone Marrow Cells ◽  
Fold Increase ◽  
Hematopoietic Progenitor Cells ◽  
Proliferative Potential ◽  
Hematopoietic Progenitor ◽  
Hla Dr

Abstract Although sustained production of committed human hematopoietic progenitor cells in long-term bone marrow cultures (LTBMC) is well documented, evidence for the generation and expansion of human primitive hematopoietic progenitor cells (PHPC) in such cultures is lacking. For that purpose, we attempted to determine if the human high proliferative potential colony-forming cell (HPP-CFC), a primitive hematopoietic marrow progenitor cell, is capable of generation and expansion in vitro. To that effect, stromal cell-free LTBMC were initiated with CD34+ HLA-DR-CD15- rhodamine 123dull bone marrow cells and were maintained with repeated addition of c-kit ligand and a synthetic interleukin-3/granulocyte-macrophage colony-stimulating factor fusion protein. By day 21 of LTBMC, a greater than twofold increase in the number of assayable HPP-CFC was detected. Furthermore, the production of HPP-CFC in LTBMC continued for up to 4 weeks, resulting in a 5.5-fold increase in HPP-CFC numbers. Weekly phenotypic analyses of cells harvested from LTBMC showed that the number of CD34+ HLA-DR- cells increased from 10(4) on day 0 to 56 CD34+ HLA-DR- cells increased from 10(4) on day 0 to 56 x 10(4) by day 21. To examine further the nature of the in vitro HPP-CFC expansion, individual HPP- CFC colonies were serially cloned. Secondary cloning of individual, day 28 primary HPP-CFC indicated that 46% of these colonies formed an average of nine secondary colony-forming unit--granulocyte-macrophage (CFU-GM)--derived colonies, whereas 43% of primary HPP-CFC gave rise to between one and six secondary HPP-CFC colonies and 6 to 26 CFU-GM. These data show that CD34+ HLA-DR- CD15- rhodamine 123dull cells represent a fraction of human bone marrow highly enriched for HPP-CFC and that based on their regeneration and proliferative capacities, a hierarchy of HPP-CFC exists. Furthermore, these studies indicate that in the presence of appropriate cytokine stimulation, it is possible to expand the number of PHPC in vitro.

scholarly journals Retrovirus-mediated transfer and expression of an allogeneic major histocompatibility complex class II DRB cDNA in swine bone marrow cultures

Blood ◽  
1993 ◽  
Vol 81 (9) ◽  
pp. 2460-2465 ◽  
Author(s):  
DW Emery ◽  
GE Shafer ◽  
EM Karson ◽  
DH Sachs ◽  
C LeGuern
Keyword(s):  
Bone Marrow ◽  
Drug Resistance ◽  
High Titer ◽  
Significant Proportion ◽  
Class Ii ◽  
Retroviral Vector ◽  
Proliferative Potential ◽  
Swine Model ◽  
Miniature Swine ◽  
Bone Marrow Cultures

Abstract The possibility of inducing transplantation tolerance by somatic gene transfer is under investigation in our miniature swine model. As a crucial step in this project, we have used a retroviral vector engineered to express both a drug-resistance gene (Neo) and a swine class II DRB cDNA to transduce porcine bone marrow (BM) cells. Analysis of cultured swine fibroblasts exposed to high-titer viral supernatants demonstrated that drug resistance had been conferred and that transferred vector sequences were transcribed appropriately. Similar transduction studies with swine BM demonstrated the transfer of drug resistance to as high as 14% of colony-forming unit-granulocyte- macrophage (CFU-GM). Using polymerase chain reaction (PCR) of cDNA, vector-derived allogeneic DRB transcripts were detected in colonies derived from primitive CFU-Mix and high proliferative potential-colony- forming cell (HPP-CFC), as well as in drug-resistant GM colonies grown from transduced bone marrow (BM) maintained in long-term BM cultures (LTBMCs) for up to 5 weeks. These results indicate that a significant proportion of both colony-forming progenitors and LTBMC-initiating cells were transduced with the DRB-recombinant retroviral vector and that both vector-derived genes were expressed in the differentiated progeny of these cells.

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.

Application of Mesenchymal Stem Cells Derived From the Umbilical Cord Instead of Bone Marrow In Hematopoietic Stem Cells Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4544-4544
Author(s):  
Ching-Tien Peng
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Proliferative Potential ◽  
Hematopoietic Stem ◽  
Cell Based Therapy

Abstract Abstract 4544 Bone marrow-derived mesenchymal stem cells (BMMSCs) have been found to enhance engraftment of hematopoietic stem cell transplantation (HSCT), plus show effect against graft-versus host disease (GVHD) because of their immunosuppressive properties. However, harvesting these cells is an invasive and painful procedure. To substitute BMMSCs from alternative sources is necessary. We intravenously infused ex vivo-expanded third-party umbilical cord-derived mesenchymal stem cells (UCMSCs) obtained from a bank 8 times in 3 patients who developed severe, steroid-resistant acute GVHD after allogeneic HSCT. The acute GVHD improved with each infusion of UCMSCs. Besides, after cotransplantation of cord blood and UCMSCs in 5 patients, we found UCMSCs enhanced absolute neutrophil counts and platelet counts recovery. No adverse effects after UCMSCs infusions were noted. We also found that UCMSCs had superior proliferative potential and greater immunosuppressive effects than BMMSCs in vitro. This is the first report of UCMSCs in human clinical application. These findings suggest UCMSCs are effective in treating aGVHD and can enhance hematopoiesis after HSCT. Considering that they are not only easy to obtain but also proliferate rapidly, UCMSCs would be the ideal candidate for cell-based therapy, especially for diseases associated with immune responses because of their immunosuppressive effects. Disclosures: No relevant conflicts of interest to declare.

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