Short-term pretreatment with low-dose hydrogen peroxide enhances the efficacy of bone marrow cells for therapeutic angiogenesis

2007 ◽  
Vol 292 (6) ◽  
pp. H2582-H2588 ◽  
Author(s):  
Masayuki Kubo ◽  
Tao-Sheng Li ◽  
Ryo Suzuki ◽  
Mako Ohshima ◽  
Shu-Lan Qin ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Bone Marrow ◽  
Low Dose ◽  
Bone Marrow Cells ◽  
Therapeutic Angiogenesis ◽  
Pcr Analysis ◽  
Endothelial Differentiation ◽  
Short Term ◽  
Marrow Cells

Therapeutic angiogenesis can be induced by the implantation of bone marrow cells (BMCs). Hydrogen peroxide (H2O2) has been shown to increase VEGF expression and to be involved in angiogenesis. We tested the hypothesis that pretreatment with H2O2 enhances the efficacy of BMCs for neovascularization. H2O2 pretreatment was done by incubating mouse BMCs in 5 μM H2O2 for 30 min, followed by washing twice with PBS. The H2O2-pretreated and untreated BMCs were then studied in vitro and in vivo. RT-PCR analysis showed that expression of VEGF and Flk-1 mRNA was significantly higher in H2O2-pretreated BMCs than in untreated BMCs after 12 and 24 h of culture ( P < 0.01). Pretreatment with H2O2 also effectively enhanced the VEGF production and endothelial differentiation from BMCs after 1 and 7 days of culture ( P < 0.05). To estimate the angiogenic potency in vivo, H2O2-pretreated or untreated BMCs were intramuscularly implanted into the ischemic hindlimbs of mice. After 14 days of treatment, many of the H2O2-pretreated BMCs were viable, showed endothelial differentiation, and were incorporated in microvessels. Conversely, the survival and incorporation of the untreated BMCs were relatively poor. Microvessel density and blood flow in the ischemic hindlimbs were significantly greater in the mice implanted with H2O2-pretreated BMCs than in those implanted with untreated BMCs ( P < 0.05). These results show that the short-term pretreatment of BMCs with low-dose H2O2 is a novel, simple, and feasible method of enhancing their angiogenic potency.

Autologous bone marrow cell implantation as therapeutic angiogenesis for ischemic hindlimb in diabetic rat model

2003 ◽  
Vol 284 (1) ◽  
pp. H66-H70 ◽  
Author(s):  
Ken Hirata ◽  
Tao-Sheng Li ◽  
Masahiko Nishida ◽  
Hiroshi Ito ◽  
Masunori Matsuzaki ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Autologous Bone Marrow ◽  
Therapeutic Angiogenesis ◽  
Endothelial Differentiation ◽  
Angiogenic Effect ◽  
Autologous Bone ◽  
Cell Implantation ◽  
Marrow Cells

The angiogenic effect induced by autologous bone marrow cell implantation (BMCI) was examined in the ischemic hindlimbs of diabetic and nondiabetic rats. Diabetes mellitus was induced by the systemic administration of streptozotocin. We investigated the production of angiogenic factors and endothelial differentiation from bone marrow cells and the native recovery of blood flow in the ischemic hindlimbs. To observe the angiogenic effect induced by BMCI treatment, 6 × 107 bone marrow cells were injected intramuscularly at six points into the ischemic limbs, and regional perfusion recovery was evaluated with colored microspheres 2 wk later. No difference was found between diabetic and nondiabetic rats in the release of angiogenic factors or endothelial differentiation from bone marrow cells in vitro. The levels of nitric oxide in plasma were significantly lower, and native perfusion recovery in the ischemic hindlimbs was significantly slower in the diabetic rats than in the nondiabetic rats. However, although perfusion recovery was achieved in the ischemic hindlimbs, there was no significant increase in systemic VEGF after BMCI treatment in either the diabetic or nondiabetic rats. Therefore, therapeutic angiogenesis induced by BMCI could be a safe and effective treatment for ischemic limb disease in diabetic patients.

scholarly journals In vivo prostaglandin E2 treatment alters the bone marrow microenvironment and preferentially expands short-term hematopoietic stem cells

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4054-4063 ◽  
Author(s):  
Benjamin J. Frisch ◽  
Rebecca L. Porter ◽  
Benjamin J. Gigliotti ◽  
Adam J. Olm-Shipman ◽  
Jonathan M. Weber ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Prostaglandin E2 ◽  
Bone Marrow Cells ◽  
Negative Impact ◽  
Hematopoietic Progenitors ◽  
Short Term ◽  
Hematopoietic Stem ◽  
Marrow Cells

Abstract Microenvironmental signals can determine hematopoietic stem cell (HSC) fate choices both directly and through stimulation of niche cells. In the bone marrow, prostaglandin E2 (PGE2) is known to affect both osteoblasts and osteoclasts, whereas in vitro it expands HSCs and affects differentiation of hematopoietic progenitors. We hypothesized that in vivo PGE2 treatment could expand HSCs through effects on both HSCs and their microenvironment. PGE2-treated mice had significantly decreased number of bone trabeculae, suggesting disruption of their microarchitecture. In addition, in vivo PGE2 increased lineage− Sca-1+ c-kit+ bone marrow cells without inhibiting their differentiation. However, detailed immunophenotyping demonstrated a PGE2-dependent increase in short-term HSCs/multipotent progenitors (ST-HSCs/MPPs) only. Bone marrow cells transplanted from PGE2 versus vehicle-treated donors had superior lymphomyeloid reconstitution, which ceased by 16 weeks, also suggesting that ST-HSCs were preferentially expanded. This was confirmed by serial transplantation studies. Thus in vivo PGE2 treatment, probably through a combination of direct and microenvironmental actions, preferentially expands ST-HSCs in the absence of marrow injury, with no negative impact on hematopoietic progenitors or long-term HSCs. These novel effects of PGE2 could be exploited clinically to increase donor ST-HSCs, which are highly proliferative and could accelerate hematopoietic recovery after stem cell transplantation.

scholarly journals Antimutagenic activity and hepatoprotective effect of anti-radiation drugs

2020 ◽  
pp. 81-82
Author(s):  
Л.П. Сычева ◽  
Л.М. Рождественский ◽  
Н.И. Лисина ◽  
Т.Г. Шлякова ◽  
В.В. Зорин
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Mechanisms Of Action ◽  
Hepatoprotective Effect ◽  
Antimutagenic Activity ◽  
Short Term ◽  
Experimental Conditions ◽  
Marrow Cells

Изучена антимутагенная активность противолучевых препаратов разного механизма действия: беталейкина, флагеллина, индралина и рибоксина в краткосрочных и хроническом экспериментах на мышах in vivo. Все препараты проявили антимутагенные свойства в клетках костного мозга, а также гепатопротекторное действие. Наибольший эффект при используемых условиях эксперимента отмечен для беталейкина и нового противолучевого препарата флагеллина. The antimutagenic activity of anti-radiation drugs betaleukin, flagellin, indraline and riboxin with different mechanisms of action was studied in short-term and chronic experiments in mice in vivo. All drugs showed antimutagenic properties in bone marrow cells, as well as hepatoprotective effect. The greatest effect under the used experimental conditions was noted for betaleukin and the new anti-radiation drug flagellin.

scholarly journals CD34+ human marrow cells that express low levels of Kit protein are enriched for long-term marrow-engrafting cells

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4136-4142 ◽  
Author(s):  
I Kawashima ◽  
ED Zanjani ◽  
G Almaida-Porada ◽  
AW Flake ◽  
H Zeng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
In Utero ◽  
Fetal Sheep ◽  
Hematopoietic Stem ◽  
Show Evidence ◽  
Marrow Cells

Using in utero transplantation into fetal sheep, we examined the capability of human bone marrow CD34+ cells fractionated based on Kit protein expression to provide long-term in vivo engraftment. Twelve hundred to 5,000 CD34+ Kit-, CD34+ Kit(low), and CD34+ Kit(high) cells were injected into a total of 14 preimmune fetal sheep recipients using the amniotic bubble technique. Six fetuses were killed in utero 1.5 months after bone marrow cell transplantation. Two fetuses receiving CD34+ Kit(low) cells showed signs of engraftment according to analysis of CD45+ cells in their bone marrow cells and karyotype studies of the colonies grown in methylcellulose culture. In contrast, two fetuses receiving CD34+ Kit(high) cells and two fetuses receiving CD34+ Kit- cells failed to show evidence of significant engraftment. Two fetuses were absorbed. A total of six fetuses receiving different cell populations were allowed to proceed to term, and the newborn sheep were serially examined for the presence of chimerism. Again, only the two sheep receiving CD34+ Kit(low) cells exhibited signs of engraftment upon serial examination. Earlier in studies of murine hematopoiesis, we have shown stage-specific changes in Kit expression by the progenitors. The studies of human cells reported here are in agreement with observations in mice, and indicate that human hematopoietic stem cells are enriched in the Kit(low) population.

Distribution of sister chromatid exchanges on the mouse chromosomes in vivo with reference to the replication properties of the X chromosome

1984 ◽  
Vol 26 (2) ◽  
pp. 152-157
Author(s):  
S. M. Singh ◽  
D. L. Reimer
Keyword(s):  
Bone Marrow ◽  
X Chromosome ◽  
Sister Chromatid ◽  
Bone Marrow Cells ◽  
Relative Length ◽  
Chromosome Length ◽  
Sister Chromatid Exchanges ◽  
Chromatid Exchanges ◽  
Marrow Cells

Frequency of sister chromatid exchanges (SCE) were recorded separately for different chromosomes from bone marrow cells of female mice of the two genetic strains (C3H/S and C57BL/6J). SCEs were evaluated following different doses of 5-bromo-2′deoxyuridine (BrdU) as nine hourly i.p. injections. The SCE per cell increased with increasing BrdU doses which was slightly higher in C3H/S than in the C57BL/6J. SCEs per cell were variable at every treatment – strain combination, possibly reflecting the heterogeneous nature of the bone marrow cells. In general, there is a positive correlation between SCE per chromosome and the relative chromosome length. Total SCEs on one of the large chromosomes (most likely the X chromosome), however, are significantly higher than expected on the basis of relative length alone. Most of this increase is attributable to one of the homologues of this chromosome, which is not in synchrony with the rest of the chromosomes and may represent the late-replicating X. These results when viewed in the light of replication properties of the heterochromatinized X, suggest a direct involvement of DNA replication in SCE formation and may argue against the replication point as the sole site for the SCEs.Key words: sister chromatid exchange, BrdU, recombination, replication, X chromosome.

scholarly journals AML cells are differentially sensitive to chemotherapy treatment in a human xenograft model

Blood ◽  
2013 ◽  
Vol 121 (12) ◽  
pp. e90-e97 ◽  
Author(s):  
Mark Wunderlich ◽  
Benjamin Mizukawa ◽  
Fu-Sheng Chou ◽  
Christina Sexton ◽  
Mahesh Shrestha ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Induction Therapy ◽  
Bone Marrow Cells ◽  
Xenograft Model ◽  
Chemotherapy Treatment ◽  
Key Points ◽  
Increased Sensitivity ◽  
Total Bone Marrow ◽  
Marrow Cells

Key Points A relevant xenograft chemotherapy model was developed by using standard AML induction therapy drugs and primary human AML patient samples. Human AML cells show significantly increased sensitivity to in vivo chemotherapy treatment compared with murine LSK and total bone marrow cells.

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