scholarly journals Flavonoid genistein protects bone marrow sinusoidal blood vessels from damage by methotrexate therapy in rats

2018 ◽  
Vol 234 (7) ◽  
pp. 11276-11286 ◽  
Author(s):  
Mohammadhossein Hassanshahi ◽  
Yu‐Wen Su ◽  
Samira Khabbazi ◽  
Chia‐Ming Fan ◽  
Ke‐Ming Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Vessels ◽  
Methotrexate Therapy

The combined application of rat bone marrow mesenchymal stem cells and bioceramic materials in the regeneration of dental pulp-like tissues

2020 ◽  
Author(s):  
Ruixue Wen ◽  
Xin Wang ◽  
Yongchao Lu ◽  
Yi Du ◽  
Xijiao Yu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Blood Vessels ◽  
Collagen Scaffold ◽  
Inflammatory Cells ◽  
Combined Application ◽  
Marrow Mesenchymal Stem Cells ◽  
Good Biocompatibility ◽  
Rat Bone

Abstract Background: To observe the effects of combined application of rat bone marrow mesenchymal stem cells (rBMSCs) and a bioceramic material on pulp-like tissue formation. Methods: Rat incisor root fragments without pulp tissues were prepared and filled with a collagen scaffold seeded with rBMSCs, while one side of the root segment was covered by a bioceramic material (iRoot BP). After culture for 12 h, the root fragments were implanted subcutaneously for 3 months. Hematoxylin and eosin (HE) staining was applied to observe biocompatibility and the formation of pulp-like tissues. Incisor root fragments were divided into three parts (BP1/3 , M1/3, and D1/3) to analyze the area and number of new vessels. Immunohistochemical staining of neuroendocrine marker PGP9.5, dentin sialophosphoprotein ( DSPP ), and vascular endothelial growth factor (VEGF) was applied to observe the formation of pulp-like tissues. Root fragments filled with the collagen scaffold only were used as a control. Results: Three months after implantation, root fragments were collected, which were surrounded by a transparent tissue membrane with a good blood supply. The root fragment cavity was filled with pink vascularized pulp-like tissue. According to HE results, iRoot BP had good biocompatibility with new pulp-like tissues and few infiltrating inflammatory cells. Increases in the number and area of new blood vessels were observed in BP1/3 compared with the other two parts. Expression of PGP9.5 and DSPP showed that the newly formed tissues were similar to normal pulp tissues. Conclusion: iRoot BP has good biocompatibility and increases the number and area of new blood vessels. The combined application of stem cells and bioceramic materials may be a better method for pulp revascularization .

Comparison Among Bone Marrow and Wheat Flour’s Mixture and Standard Treatment on Healing Second-Degree Burn Wound in Rats

2020 ◽  
Author(s):  
Saboreh Jafari ◽  
Rostam Jalali ◽  
Cyrus Jalili ◽  
Tahereh Jamshidpoor
Keyword(s):  
Bone Marrow ◽  
Blood Vessels ◽  
Wheat Flour ◽  
Standard Treatment ◽  
Treated Group ◽  
Hair Follicles ◽  
Silver Sulfadiazine ◽  
Male Rats ◽  
Control Group ◽  
Burn Wound

Abstract The treatment of extensive skin burns remains as a challenge for health care personnel. This study aimed to compare the combination of bone marrow and wheat flour with standard treatment on animal models. In this experimental study, 45 male rats were randomly assigned into three groups as follows: The first group was control (no treatment), the second group received bone marrow and wheat flour combination topically, and the third group received standard treatment (1% silver sulfadiazine). The treatment lasted for up to 21 days. On the 22nd day, the rats were killed. The number of blood vessels and hair follicles was measured in the burn wound bed. The area and depth of the wound were also measured. Data were analyzed using SPSS software version 16. The results showed that, complete closure of the wound was better in the bone marrow treated group compared with the group receiving the silver sulfadiazine and the control group. Furthermore, the wound healing was better in the silver sulfadiazine group compared with the control group. Microscopic examination revealed a significant increase in the number of hair follicles and blood vessels in the bone marrow and silver groups compared with the control group. The results showed that, the group treated with bone marrow, because of the presence of mesenchymal and stem cells can cause stimulating angiogenesis and producing vegetative tissue, hence it improved maturation, shrinkage, and contraction of the wound in comparison with the silver sulfadiazine and control groups

Growth in vitro of blood vessels from bone marrow of adult chickens

1951 ◽  
Vol 89 (2) ◽  
pp. 321-345 ◽  
Author(s):  
Joan Fulton White ◽  
Mary Stearns Parshley
Keyword(s):  
Bone Marrow ◽  
Blood Vessels

Pleiotrophin Is Highly Produced by Myeloma and Breast Cancer and Transdifferentiates Human Monocytes into Endothelial Cells That Are Incorporated into Tumoral Blood Vessels.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1269-1269
Author(s):  
Haiming Chen ◽  
Richard A. Campbell ◽  
Mingjie Li ◽  
Melinda S. Gordon ◽  
Dror Shalitin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Blood Vessels ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Human Monocytes ◽  
Endothelial Gene Expression

Abstract We have previously shown that multiple myeloma (MM) patients express pleiotrophin (PTN) and it is found at high levels in MM serum as well as PTN is a key factor in the transdifferentiation of monocytes into endothelial cells. We determined the level of PTN expression in myeloma and breast cancer and determined whether PTN produced by these tumor cells could induce endothelial cell expression in human monocytes. Both myeloma and breast cancer cells produced high levels of PTN and secreted this growth factor into the culture medium whereas normal bone marrow showed no expression of this protein. Next, MM cell lines, human bone marrow (BM) from MM patients or control subjects or breast cancer cells were cultured with CD14+ PBMCs using transwell culture plates coated with collagen I. CD14+ monocytes exposed to cells from MM cell lines or fresh BM or breast cancer cells showed expression of endothelial genes (Flk-1, Tie-2, CD144, and vWF) and lost expression of monocyte genes (c-fms). Induction of endothelial gene expression was blocked with an anti-PTN antibody. In contrast, CD14+ cells exposed to normal bone marrow as well as cell lines lacking PTN expression did not show endothelial gene expression. We determined whether human monocytes could be incorporated in vivo as vascular endothelium within human tumors that express PTN. Human myeloma LAGλ-1 cells which highly express and secrete PTN were mixed with THP1 monocytes transduced with the green fluorescent protein (GFP) gene and injected subcutaneously into SCID mice. Mice were sacrificed 6 weeks later and tumor was fixed and frozen sections. MM cells or THP1 monocytes alone did not demonstrate the presence of GFP+ blood vessels. Notably, GFP+ THP1 cells were found in blood vessels within the PTN-expressing LAGλ-1 tumor in animals injected with both cells together. When GFP+h2Kd- blood vessels were stained for anti-human and anti-mouse CD31, 60% of the endothelial cells stained positive for human CD31 and the remaining cells stained positive for mouse CD31 whereas none of these cells stained positive for both mouse and human markers. These results show that the blood vessels containing GFP+ cells do not result from fused cells. In addition, an anti-PTN antibody but not control IgG antibody blocks the incorporation of GFP+ cells into the vasculature of the LAGλ-1 tumors. Staining of serial sections with anti-Tie-2 and CD31 antibodies showed a similar distribution pattern. We further examined endothelial gene expression in these in vivo-generated samples using RT-PCR. The results showed that the THP1 monocytes or LAGλ-1 tumor cells alone did not express endothelial genes whereas THP1 monocytes mixed with PTN-expressing LAGλ-1 showed endothelial gene expression. This endothelial gene expression was blocked by anti-PTN antibody. These data show that hematologic and solid tumors through expression of PTN support new blood vessel formation by the transdifferentiation of monocytes into endothelial cells and provide a new potential target for inhibiting blood vessel formation in solid and liquid tumors.

Hemangiogenic Role of ELF4 in Bone Marrow Post Myeloablation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1783-1783
Author(s):  
Mariela Sivina ◽  
Takeshi Yamada ◽  
Natalie Dang ◽  
H. Daniel Lacorazza
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Hematopoietic Stem Cells ◽  
Blood Vessels ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Bone Marrow Cells ◽  
Hematopoietic Stem ◽  
Huvec Cells

Abstract Bone marrow suppression is an important cause of death in patients exposed to radiation or in cancer patients treated with conventional chemotherapeutic agents. Myeloablative treatments (i.e. 5-fluorouracil administration) lead to apoptosis of blood forming cells and to regression of blood vessels in bone marrow. It is well known that hematological recovery post-bone marrow insult depends on the capacity of hematopoietic stem cells to regenerate the entire hematopoietic system, however, the transcriptional machinery involved in the regeneration of sinusoidal blood vessels in bone marrow from endothelial progenitor cells is largely unknown. Endothelial cells express the Tie2 receptor tyrosine kinase (a.k.a. Tek), which is involved in the angiogenic remodeling and vessel stabilization. Gene targeting of Tie2 showed that it is not required for differentiation and proliferation of definitive hematopoietic lineages in the embryo although Tie2 is needed during postnatal bone marrow hematopoiesis. ELF is a subgroup of the ETS family of transcription factors composed by ELF1, ELF2 (a.k.a. NERF), ELF3, ELF4 (a.k.a. MEF) and ELF5. ELF1 and ELF2 have been shown to regulate Tie2 expression in vitro. Recently we showed that ELF4 modulates the exit of hematopoietic stem cells (HSC) from quiescence (Lacorazza et al., Cancer Cell2006, 9:175–187). Given the high homology between ELF1 and ELF4 and the same origin of HSC and endothelial progenitor cells, we hypothesize that ELF4 regulates proliferation and Tie2 expression of endothelial cells. We used a luciferase gene reporter system in COS-7 and HEK cells to examine the capacity of ELF proteins to activate Tie2. ELF4 is the strongest activator of Tie2 expression following the hierarchy ELF4>ELF1>ELF2 variant 1>ELF2 variant 2. Site directed mutagenesis of each of the five ETS-binding sites (EBS) present in the Tie2 promoter shows that ELF4 binds preferentially to EBS 1, 3 and 5. Binding of ELF4 to the Tie2 promoter was confirmed by chromatin immunoprecipitation and EMSA. Although Elf1 gene expression is essentially normal in Elf4−/− bone marrow cells collected after 5-FU treatment, we detected diminished Tie2 expression compared to Elf4+/+ bone marrow cells. The association of this effect to human endothelial cells derived from umbilical cord (HUVEC cells) was investigated. All-trans retinoic acid (ATRA) and vascular-endothelial growth factor (VEGF) induced ELF4 expression in HUVEC cells in a dose and time dependent manner which was followed by increased Tie2 expression, suggesting that expression of ELF4 is modulated by angiogenic signals. Moreover, endothelial cells treated with ATRA showed rapid wound colonization in a wound assay. Expression of the pan-endothelial marker MECA-32 was determined by immunohistochemistry to correlate Tie2 with the regeneration of blood vessels: myeloablated Elf4−/− femurs exhibited a reduction of MECA-32 positive arterioles. Finally, temporal and spatial expression of Tie2 during hematological recovery post ablation was measured in bone marrow using transgenic Tie2-LacZ mice crossed to Elf4−/− mice. Collectively, our data suggests that ELF4 regulates Tie2 expression in endothelial cells but most importantly their proliferative capacity in response to angiogenic signals.

Acute Myeloid Leukemia Cells Generate Leukemic Endothelial Cells with Leukemogenic Potential: Blood Vessels As Sanctuaries for Leukemia Relapse

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 241-241
Author(s):  
Christopher R Cogle ◽  
Gerard J Madlambayan ◽  
Devorah C Goldman ◽  
Azzah Al Masri ◽  
Ronald P. Leon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Surface Proteins ◽  
Nsg Mice ◽  
Acute Myeloid ◽  
Marrow Cells

Abstract Abstract 241 Human hematopoietic stem cells (HSCs) possess hemangioblast activity, which is defined as the ability to generate both blood and endothelium. Whether malignant HSC counterparts such as acute myeloid leukemia (AML) also display this bipotentiality remains to be defined. To test the hemangioblast potential of AML cells we first cultured primary human AML bone marrow in conditions established by Yoder and colleagues that support the growth of functional endothelial cell (EC) progenitors. AML cultured in endothelial colony forming cell (ECFC) media generated endothelial progenitor cell colonies that showed uptake of acetylated LDL and expressed several EC surface proteins, including CD105, CD146, UEA-1 and CD144. Importantly, ECFCs derived from AML bone marrow no longer expressed CD45 or myeloid surface proteins such as CD14. When placed in Matrigel, these AML derived ECFC generated capillary-like, tubular structures. Moreover, these ECFCs contained cytogenetic mutations associated with their parental leukemias. Thus, under the appropriate conditions, AML bone marrow cells can generate cells with an endothelial-like phenotype and harboring leukemia specific mutations that will be referred to as ‘L-ECFC.' To functionally define leukemia hemangioblast activity, a xenograft model of AML was employed. Sublethally irradiated NOD/scid/IL2Rγ−/− (NSG) mice were transplanted with primary human AML cells and then sacrificed at 8–36 weeks after transplant. Significant accumulations of human AML cells were found in perivascular regions of the liver. Both tight coupling and bona fide cell fusion between AML and ECs was observed. AML derived EC that were integrated into portal vein endothelium showed induction of CD105 expression Follow-up AML xenotransplant experiments with BrdU labeling revealed almost four-fold fewer (6%) of the AML cells incorporated within blood vessels were BrdU+, as compared to AML cells not integrated in blood vessels (22%) (P=0.01). These results suggest that AML cell incorporation within the endovascular lining induces cell quiescence. Thus, leukemia-integrated ECs may be less susceptible to cell cycle active agents like cytarabine. Results from these experiments also raised the possibility that AML cells adopting an endothelial-like phenotype may serve as a reservoir for leukemic relapse. To test this hypothesis, we injected CD105+CD45- L-ECFC derived from AML patients into NSG mice. These L-ECFC generated colonies of human CD105+CD45- within spleens and bone marrow of recipient mice. We also found a distinct population of human CD45+CD19- cells comprising 5–10% of bone marrow cells. Leukemia-derived cells were confirmed by detection of cytogenetically mutant cells consistent with the parent leukemia (e.g., MLL duplications). In conclusion, this study demonstrates that AML cells can functionally generate leukemic ECs that become quiescent after incorporation in blood vessel networks and can re-emerge with a leukemogenic phenotype. Together, our results raise the strong possibility that AML cells exhibit functional hemangioblast activity and that vascular endothelium may serve as a clinically important sanctuary for occult leukemia. Our data also support endothelial cell targeting strategies as a means to eradicate AML. Disclosures: No relevant conflicts of interest to declare.

Hematopoietic Functions of the Tumor Supressor Von Hippel Lindau (VHL) in the Etiology of Hemangioblastoma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2425-2425
Author(s):  
Hannah L Bader ◽  
Tracy Pritchett ◽  
Tien Hsu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Mouse Model ◽  
Gall Bladder ◽  
Blood Vessels ◽  
Progenitor Cells ◽  
Liver Lesions ◽  
Endothelial Lining ◽  
Knock Out

Abstract Abstract 2425 Germline heterozygous mutation in the VHL tumor suppressor gene is the underlying genetic defect in VHL disease. Cancer arises when the function of the remaining wildtype allele is lost. VHL patients are prone to develop renal cell carcinoma of the clear cell type (ccRCC) and hemangioblastoma (HB). VHL mutations underlie also the majority of sporadic ccRCC and HB. HB are highly vascularized tumors of the central nervous system. However, it is unclear from which tissue HB arise (reviewed in (1)). Although HB are sometimes described as vascular tumors, inactivation of both VHL alleles has been detected only in the stromal component, suggesting that abnormal angiogenesis is driven by cytokines released from the tumor rather than by VHL inactivation in the endothelium. There is evidence that hematopoietic stem cells or early progenitor cells are involved in the formation of HB. For instance, advanced HB are frequently accompanied by extramedullary erythropoiesis (EME) (2,3). Previously, overgrowth of blood vessels (hemangioma) has been observed in the liver of constitutive heterozygous Vhl knock-out mice, and in a hepatocyte specific Vhl conditional knock-out (albumin-cre) (4). Here, we present a mouse model that may shed light on another aspect of HB, e.g. EME. We used HOXB7-cre for the conditional deletion of VHL in a subset of kidney tubules (HOXB7-Vhl mice). Interestingly, we found that these mice developed not only a kidney phenotype, but also liver lesions. At 2–3 months of age, blood filled bulges developed close to the gall bladder (see Fig. 1A). Superficially, these lesions resembled previously described hemangiomas. However, histology revealed large blood lakunae that were not lined by blood vessels (Fig 1B). Hence, lesions appeared to arise not due to an overgrowth of blood vessels, but due to EME, with massive accumulation of red blood cells surrounding foci of nucleated progenitor cells (Fig. 1C). Fig. 1. Liver lesions in HOXB7-Vhl mice. A: Blood filled bulges form close to the gall bladder (arrowheads). B, C: Histology. Note lakunae of blood (L) without endothelial lining (B), and foci of progenitor cells (arrow in C). Fig. 1. Liver lesions in HOXB7-Vhl mice. A: Blood filled bulges form close to the gall bladder (arrowheads). B, C: Histology. Note lakunae of blood (L) without endothelial lining (B), and foci of progenitor cells (arrow in C). CFU assays with liver cell suspensions confirmed EME: there was a significant increase in the number of liver BFUs in HOXB7-Vhl mice. HOXB7-Vhl mice had also elevated levels of EPO in the serum, and flow cytometry showed an increase in TER119+CD71+ erythrocyte progenitors in the spleen, but not the bone marrow. Despite EME and elevated EPO levels, HOXB7-VHL mice displayed only rarely polycythemia. In this context, it is noteworthy that VHL patients also present frequently with elevated EPO levels, without developing polycythemia. Interestingly, the majority of HoxB7-VHL mice developed thrombocytopenia, possibly due to the leakiness of the blood vasculature in the liver lesions. However, flow cytometry showed also a decrease in megakaryocytes (CD41+) in both bone marrow and spleen, and in addition to an increase of erythrocyte progenitors, an increase in TER119+CD41+ common megakaryocyte-erythrocyte progenitors (MEP) in the spleen. It is therefore possible that differentiation of the MEP is shifted towards the erythrocyte lineage in the HOXB7-Vhl mouse. We found no evidence of Vhl deletion in the liver of HOXB7-Vhl mice using LacZ reporter mice. Our mouse model suggests therefore a systemic etiology of HB. One of the best known functions of VHL is the negative regulation of the hypoxia-inducible factor (HIF). Besides EPO, the chemokine receptor CXCR4 is also a known HIF-responsive gene (5) that could be potentially disregulated by Vhl deletion. Furthermore, preliminary data indicate that constitutive heterozygous VHL mice show 50% mortality in transplantation experiments, irrespective of the genotype of transplanted stem cells (e.g. wt or VHL +/−). Hence, in addition to cell autonomous and systemic mechanisms, defects in the bone marrow environment may underlie hematologic presentations of VHL deficiency. Disclosures: No relevant conflicts of interest to declare.

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