scholarly journals Studies of the Hemopoietic Microenvironment. I. Changes in the Microvascular System and Stroma During Erythropoietic Regeneration and Suppression in the Spleens of CF1 Mice

Blood ◽  
1972 ◽  
Vol 39 (5) ◽  
pp. 697-712 ◽  
Author(s):  
Robert S. McCuskey ◽  
Howard A. Meineke ◽  
Samuel F. Townsend
Keyword(s):  
Bone Marrow ◽  
Blood Flow ◽  
Linear Velocity ◽  
Proliferating Cells ◽  
Hemopoietic Microenvironment ◽  
Murine Spleen ◽  
Flow Through ◽  
Tissue Compartments ◽  
Red Pulp

Abstract Specific alterations in the microvascular and connective tissue compartments of the hemopoietic microenvironment have been examined during erythropoietic regeneration and suppression in the murine spleen and bone marrow using in vivo microscopic and histochemical methods. The results have confirmed the concept of specific hemopoietic microenvironments and have demonstrated specific alterations in the microenvironment during erythropoietic stimulation and repression. Elevated erythropoiesis in the splenic red pulp is accompanied by an elevation in blood flow through the microvascular system. Both the linear velocity of flow and the number of sinusoids with blood flow in them increased significantly. In contrast, erythropoietic repression was accompanied by a decreased linear velocity of blood flow, as well as a marked increase in the amount of blood being stored in the splenic sinusoids. This also was the picture when diffuse granulopoiesis was present in the red pulp, or when granuloid or undifferentiated colonies were present. The chemical composition of the stroma in the spleen and bone marrow also varied during states of hemopoietic activity and, in addition, there were differences in the composition of the stroma between these two organs. In both organs, foci of early proliferating cells were enveloped by a coating of sulfated acid mucopolysaccharide. This coat persisted on cells in later stages of granulopoiesis but not on cells in the later stages of erythropoiesis. The latter were enveloped with a coating of neutral mucopolysaccharide. A tentative hypothesis to explain the mechanisms involved in producing these changes is discussed.

scholarly journals Studies of the Hemopoietic Microenvironment. II. Effect of Erythropoietin on the Splenic Microvasculature of Polycythemic CF1 Mice

Blood ◽  
1972 ◽  
Vol 39 (6) ◽  
pp. 809-813 ◽  
Author(s):  
Robert S. McCuskey ◽  
Howard A. Meineke ◽  
Stephen M. Kaplan
Keyword(s):  
Stem Cells ◽  
Blood Flow ◽  
Single Dose ◽  
Pancreatic Tissue ◽  
Linear Velocity ◽  
Hemopoietic Microenvironment ◽  
Microvascular Response ◽  
Flow Through

Abstract The effect of erythropoietin on the splenic microvascular system of polycythemic CF1 mice was studied using in vivo microscopic methods. Administration of a single dose (3 U) of erythropoietin resulted in an increase in the linear velocity of blood flow through the splenic sinusoids and a reduction in the number of sinusoids storing blood. This response was first seen 4-6 hr after injection; it persisted for 48 hr and was reduced markedly by 72 hr. By 120 hr the spleens were indistinguishable from controls. The response was specific for erythrogenic tissue, since no response was seen in the adjacent nonerythropoietic pancreatic tissue. The results suggest that the splenic microvascular response to erythropoietin may be indirect and may be mediated by the release of a vasoactive metabolite from the erythrogenic tissues surrounding the sinusoids. Erythropoietin-sensitive stem cells are suggested to be the source of such a metabolite.

pH environmental of red cells in the spleen

1976 ◽  
Vol 231 (6) ◽  
pp. 1672-1678 ◽  
Author(s):  
MJ Levesque ◽  
AC Groom
Keyword(s):  
Splenic Tissue ◽  
Red Cells ◽  
Red Cell ◽  
Cat Spleen ◽  
Flow Through ◽  
Red Pulp ◽  
Reduced Flow

Intrasplenic pH in vivo was deduced from measurements on blood drained from cat spleen during contraction with the inflow occluded. The pH of blood in the red pulp is normally 7.20, but stasis or reduced flow through the pulp causes pH to fall toward 6.8. The splenic pulp contains blood of high hematocrit. To evaluate the role of buffering by the red cells themselves, intrasplenic p/ in red cell-free spleens was, therefore, estimated atering and leaving the spleen during red cell washout. At inflow pH less than 6.8 the outflow pH was raised, at inflow pH = 6.8 there was no change, b,t at inflow pH greater than 6.8 the outflow pH was lowered. These results indicate that the pH environment of red cells in the spleen results indicate that the pH environment of red cells in the spleen results from the interplay of two separate factors: i) pH-determining elements of the splenic tissue that buffer at 6.8, and ii) buffering provided by red cells passing through the pulp.

Quantification of in vitro and in vivo energy metabolism of the gastrointestinal tract of fed or fasted sheep

1993 ◽  
Vol 73 (4) ◽  
pp. 855-868 ◽  
Author(s):  
J. M. Kelly ◽  
B. G. Southorn ◽  
C. E. Kelly ◽  
L. P. Milligan ◽  
B. W. McBride
Keyword(s):  
Blood Flow ◽  
Gastrointestinal Tract ◽  
Portal Blood Flow ◽  
Whole Body ◽  
Hepatic Portal Vein ◽  
Flow Through ◽  
Hepatic Portal ◽  
Ouabain Inhibition

The effect of level of nutrition on in vitro and in vivo O2 consumption by the gastrointestinal tract in four nonlactating, nonpregnant ewes catheterized in the anterior mesenteric vein, hepatic portal vein and mesenteric artery with duodenal cannulae was investigated. Animals were fed a pelleted ration at maintenance (M) or twice maintenance (2M) or fasted (F) subsequent to the M measurement. Duodenal in vitro O2, ouabain-sensitive O2 (OSO2) and cycloheximide-sensitive O2 (CSO2) consumption was determined polarographically using a YSI O2 monitor; whole-gut O2 consumption was determined as (arterio-venous difference of O2 concentration) × (blood flow through the PV). Whole-body O2 consumption was determined using indirect calorimetry. Ewes fed 2M exhibited higher (P < 0.10) whole-body O2 consumption than either M or F ewes. Ewes fed M and 2M had higher (P < 0.10) duodenal in vitro O2 and ouabain-insensitive O2 (OIO2) consumption than F ewes. Hepatic portal blood flow was directly proportional to level of intake (P < 0.10): it was lowest for F ewes (81.0 L h−1), intermediate for M ewes (97.7 L h−1) and highest for 2M ewes (122.5 L h−1). Ouabain inhibition of O2 consumption by portal-drained viscera (PDV) was highest in M ewes and lowest in 2M ewes (P < 0.10). CSO2 consumption by the entire PDV was not affected by level of intake, corresponding to no change in OIO2 consumption by the PDV. As a proportion of whole-body O2 consumption, total O2, OSO2 and cycloheximide-insensitive O2 consumption by the PDV was higher in F ewes than in 2M ewes (P < 0.10). Fasted ewes expended a greater proportion of whole-body O2 consumption on gastrointestinal energetics than did 2M ewes. Key words: Sheep, gastrointestinal oxygen consumption, sodium–potassium ATPase, protein synthesis

Umbilical Cord Blood CD133+ Stem Cells Exhibit Vasculogenic Capacity In Vitro and Augment Neovasculogenesis In Vivo in a Murine Model of Vascular Ischemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1790-1790
Author(s):  
M.R. Finney ◽  
L.R. Fanning ◽  
P.J. Vincent ◽  
D.G. Winter ◽  
M.A. Hoffman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Blood Flow ◽  
Cord Blood ◽  
Umbilical Cord Blood ◽  
Hind Limb ◽  
Capillary Density ◽  
Functional Assays

Abstract Recent reports have utilized a variety of cell types for cellular therapy in mediating therapeutic angiogenesis in response to ischemia. We sought to assess the vasculogeneic potential of selected CD133+ hematopoietic stem cells (HSC) from umbilical cord blood (UCB) utilizing in vitro functional assays and an in vivo murine hind-limb ischemia model. Methods & Results: Mononuclear cells (MNC) from UCB or bone marrow (BM) were incubated with CD133+ conjugated magnetic beads, followed by automated sorting through magnetic columns (Miltenyi). Routine yield of CD133+ cells was 0.5±0.2% of UCB MNC and 0.7±0.3% of BM MNC, with a purity of 79±2% (UCB, n=30) and 84±5% (BM, n=12). Surface expression in the UCB CD133+ population was 3.6±1.5% KDR(VEGFR2), 8.7± 3.8% CXCR4 and 22.7±2.8% CD105 compared to 9.2±1.8% KDR, 14.4±1.3% CXCR4 and 23.7±2.3% CD105 in the BM CD133+ population. We measured chemotactic migration of cells towards SDF-1 (100ng/mL) compared to control wells containing media alone. The fold increase over control was 4.9±2.9 UCB MNC, 1.8±0.7 UCB CD133+ and 8.3±1.7 BM CD133+ (n=3). Angiogenic protein assays of CD133+ cells demonstrated elevated levels of IL-8 production as compared to MNC (103+/−380 pg/mL greater in CD133+ than MNC from the same UCB unit) when cultured for 24h in basal media. NOD/SCID mice underwent ligation of the right femoral artery and were given cells or vehicle control via intracardiac injection immediately following injury. Mice were given 1 x 106 MNC or 0.5 x 106 CD133+ cells. Laser Doppler flow measurements were obtained from both limbs each week for 6 weeks and the ratio of perfusion in the ischemic/healthy limb was calculated. At 28 days, perfusion ratios were statistically higher in study groups receiving UCB CD133+ cells, 0.55±0.06 (n=9), BM CD133+ cells 0.47±0.07 (n=8), BM MNC 0.48±0.8 (n=6) compared to cytokine controls 0.37±0.03 (n=12, p<0.05). Mice receiving UCB MNC did not show statistically significant improvement in measured blood flow over control animals 0.42±0.05 (n=8, p=0.34). At sacrifice, bone marrow was harvested to assess engraftment of human cells by flow cytometric analysis. Mice injected with UCB CD133+ cells showed 19±4.9% positive huCD45 cells compared to 2.5±0.6% for UCB MNC, 1.6±0.4% for BM CD133+ cells and 2.3±0.3% for BM MNC (n=3). Histological studies from day 42 tissue samples of muscle distal to arterial ligation were evaluated for capillary density. Control animals had capillary density of 131±6.9 cells/mm2. Capillary density was statistically higher that controls in animals receiving UCB CD133+ (320±18; p<0.0001), BM CD133++ (183±9.3; p<0.0001), and UCB MNC (164±10.5; p=0.011). Mice treated with BM MNC (135±9.4) did not have a statistically significant increase in capillary density from controls (p=0.73). In addition, animals treated with either UCB or BM-derived CD133+ cells had statistically higher capillary density than unselected MNC (p=<0.0001 and p=0.0004, respectively). Conclusions: In vitro functional assays showed that UCB-derived CD133+ HSC demonstrate enhanced homing capability (migration) as well as the potential for cellular recruitment (via IL-8 production) for angiogenesis in response to ischemia. Furthermore, UCB derived CD133+ HSC mediate significantly improved blood flow in an in vivo murine hind-limb injury model of ischemia, indicating the greater vasculogenic potential of selected CD133+ cells from of this stem cell source.

scholarly journals THE FACTORS CONCERNED IN THE APPEARANCE OF NUCLEATED RED BLOOD CORPUSCLES IN THE PERIPHERAL BLOOD

1918 ◽  
Vol 27 (2) ◽  
pp. 249-272 ◽  
Author(s):  
Cecil K. Drinker ◽  
Katherine R. Drinker ◽  
Henry A. Kreutzmann
Keyword(s):  
Bone Marrow ◽  
Blood Flow ◽  
Peripheral Blood ◽  
Careful Analysis ◽  
Red Cells ◽  
Accurate Expression ◽  
Vasomotor Nerves ◽  
Flow Through ◽  
Increased Blood Flow

1. Increase in circulatory rate caused by hard exercise has no power to dislocate nucleated red cells from the bone marrow either in normal, in anemic, in hyperplastic, or in anemic and hyperplastic animals. 2. In anemic and hyperplastic animals pseudocrises of nucleated red cells can be produced at certain periods by hard exercise, but careful analysis leads inevitably to the conclusion that the increase in these cells is merely a more accurate expression of circulatory content at the time of the procedure. 3. Section of the vasomotor nerves to the four limbs with consequent dilatation of the marrow vessels and increased blood flow through the tissue does not result in the freeing of nucleated red cells from the bone marrow.

scholarly journals Microscopy of Living Bone Marrow In Situ. II. Influence of the Microenvironment on Hemopoiesis

Blood ◽  
1971 ◽  
Vol 38 (1) ◽  
pp. 96-107 ◽  
Author(s):  
SAMUEL G. MCCLUGAGE ◽  
ROBERT S. MCCUSKEY ◽  
HOWARD A. MEINEKE
Keyword(s):  
Bone Marrow ◽  
Intimate Relationship ◽  
Fat Cells ◽  
Proliferating Cells ◽  
Dynamic Changes ◽  
Cellular Compartment ◽  
Local Factors ◽  
Living Bone

Abstract The present study examined in vivo the dynamic changes of hypocellular bone marrow during increased hemopoietic activity induced by phlebotomy or administration of erythropoietin. During increased hemopoietic activity, large venules and venous sinusoids located within the marrow spaces were replaced by dilated or polygonal networks of sinusoids supplied by small arterioles or capillaries that coursed from surrounding spicules of bone into the marrow spaces. An increased cellularity (hemopoietic and fat cells) was associated with this change in vascularity. The results suggest the presence of two functional parts of the microvascular system in bone marrow. The first is associated with hemopoietic areas of the marrow and is erythropoietin-sensitive; the second, with regeneration and resorption of bone. The presence of cancellous bone and the morphology of the microvascular system may determine the extent of hemopoietic activity of bone marrow. During increased hemopoietic activity, the intimate relationship between the microvascular system, bone spicules, and the developing cellular compartment suggests local factors resident in bone are transported to these proliferating cells to exert a hemopoietic effect.

Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches

Blood ◽  
2010 ◽  
Vol 116 (3) ◽  
pp. 375-385 ◽  
Author(s):  
Ingrid G. Winkler ◽  
Valérie Barbier ◽  
Robert Wadley ◽  
Andrew C. W. Zannettino ◽  
Sharon Williams ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Flow ◽  
Stromal Cells ◽  
Blood Perfusion ◽  
Low Oxygen ◽  
Hematopoietic Stem ◽  
Single Host ◽  
Differentiation Stage

Abstract Hematopoietic stem cell (HSC) niches have been reported at the endosteum or adjacent to bone marrow (BM) vasculature. To investigate functional attributes of these niches, mice were perfused with Hoechst 33342 (Ho) in vivo before BM cell collection in presence of pump inhibitors and antibody stained. We report that the position of phenotypic HSCs, multipotent and myeloid progenitors relative to blood flow, follows a hierarchy reflecting differentiation stage, whereas mesenchymal stromal cells are perivascular. Furthermore, during granulocyte colony-stimulating factor–induced mobilization, HSCs migrated closer to blood flow, whereas stromal cells did not. Interestingly, phenotypic Lin−Sca1+KIT+CD41−CD48−CD150+ HSCs segregated into 2 groups (Honeg or Homed), based on degree of blood/Ho perfusion of their niche. HSCs capable of serial transplantation and long-term bromodeoxyuridine label retention were enriched in Honeg HSCs, whereas Homed HSCs cycled more frequently and only reconstituted a single host. This suggests that the most potent HSC niches are enriched in locally secreted factors and low oxygen tension due to negligible blood flow. Importantly, blood perfusion of niches correlates better with HSC function than absolute distance from vasculature. This technique enables prospective isolation of serially reconstituting HSCs distinct from other less potent HSCs of the same phenotype, based on the in vivo niche in which they reside.

scholarly journals Local IP3 receptor–mediated Ca2+ signals compound to direct blood flow in brain capillaries

2021 ◽  
Vol 7 (30) ◽  
pp. eabh0101
Author(s):  
Thomas A. Longden ◽  
Amreen Mughal ◽  
Grant W. Hennig ◽  
Osama F. Harraz ◽  
Bo Shui ◽  
...  
Keyword(s):  
Blood Flow ◽  
High Amplitude ◽  
Ip3 Receptor ◽  
Brain Capillary ◽  
Capillary Endothelial Cells ◽  
Compound Events ◽  
Flow Through ◽  
Large Clusters ◽  
Small Clusters

Healthy brain function depends on the finely tuned spatial and temporal delivery of blood-borne nutrients to active neurons via the vast, dense capillary network. Here, using in vivo imaging in anesthetized mice, we reveal that brain capillary endothelial cells control blood flow through a hierarchy of IP3 receptor–mediated Ca2+ events, ranging from small, subsecond protoevents, reflecting Ca2+ release through a small number of channels, to high-amplitude, sustained (up to ~1 min) compound events mediated by large clusters of channels. These frequent (~5000 events/s per microliter of cortex) Ca2+ signals are driven by neuronal activity, which engages Gq protein–coupled receptor signaling, and are enhanced by Ca2+ entry through TRPV4 channels. The resulting Ca2+-dependent synthesis of nitric oxide increases local blood flow selectively through affected capillary branches, providing a mechanism for high-resolution control of blood flow to small clusters of neurons.

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