Generation of Live Young from Xenografted Mouse Ovaries

Science (New York, N.Y.). Sep, 2002  |  Pubmed ID: 12351780

Fetal Responses to Maternal and Intra-amniotic Lipopolysaccharide Administration in Sheep

Biology of Reproduction. May, 2003  |  Pubmed ID: 12606477

A link between intrauterine infection and premature labor is widely accepted, yet the fetal inflammatory responses to such infections are not well understood. Our aim was to use a sheep model in which an inflammatory state was induced by lipopolysaccharide (LPS) administration during pregnancy to the maternal systemic, intra-amniotic or extra-amniotic compartments. Fetal and maternal blood gases and uterine electromyographic activity along with fetal and maternal circulating concentrations of prostaglandins PGE2 and PGFM, cortisol, and interleukin-6 were determined. Maternal systemic LPS treatment resulted in mild maternal hypoxemia, a rise in temperature, greater fetal hypoxemia, and a marked rise in fetal cortisol and PGE2 concentrations that persisted for 48 h. Intra-amniotic administration of LPS at doses higher than those used systemically caused an increase in fetal cortisol and PGE2 concentrations as well as a rise in uterine activity, but these were lesser in magnitude. Extra-amniotic LPS administration caused no overt fetal or maternal inflammatory responses. We conclude that maternal LPS treatment markedly elevated fetal cortisol and PGE2 concentrations. This may be a potential protective mechanism that aids the fetus in the event of premature delivery. The attenuated fetal response to intra-amniotic LPS treatment, despite the much higher dose used, may support a role for the amniotic fluid in protecting the fetus from endotoxin exposure during pregnancy.

Maternal Serum Activin A Levels in Association with Intrauterine Fetal Growth Restriction

BJOG : an International Journal of Obstetrics and Gynaecology. Mar, 2003  |  Pubmed ID: 12628273

To assess maternal serum activin A as a potential marker of fetal growth restriction.

The Effect of Prenatal Hypoxia and Malnutrition on Memory Consolidation in the Chick

Brain Research. Developmental Brain Research. Jan, 2004  |  Pubmed ID: 14757525

The contribution of hypoxia and malnutrition to cognitive impairments was investigated in chicks incubated in conditions of reduced gas exchange. Previous research has shown that reducing gas exchange during incubation by wrapping half the eggshell with an impermeable membrane results in impaired cognitive ability in young chicks. The results were interpreted within a three stage sequential model of memory using discriminated bead avoidance learning. Reducing gas exchange for 4 days from day 10 or 14, of the 21-day incubation, inhibits memory formation and consolidation into permanent storage. The nature of the cognitive deficit depended on the timing of the insult. Environmental hypoxia (14% oxygen), induced from days 10 to 14 and from days 14 to 18, replicated the memory deficits found previously when eggs were partially wrapped with a membrane. Oxygen is necessary to break down food and to provide energy to build tissue proteins, and therefore hypoxia (partial wrapping or environmental incubation) may indirectly cause malnutrition. Malnutrition, induced by removing 5%, 7.5% or 10% albumin from the egg prior to incubation, had no significant effect on memory consolidation. Raised corticosterone levels occurred in chicks malnourished by 5% and 7.5%, but brain sparing was only evident in chicks with 7.5% albumin removal. Hatch rates were very low in 10% malnourished chicks. Using the chick as a model of prenatal stress, we have been able to isolate the effects of hypoxia from contributing maternal factors.

Cardiovascular and Endocrine Responses to Cutaneous Electrical Stimulation After Fentanyl in the Ovine Fetus

American Journal of Obstetrics and Gynecology. Mar, 2004  |  Pubmed ID: 15042022

The purpose of this study was to determine whether physical stimulation is stressful to the ovine fetus, as judged from physiologic changes that are similar to those reported for other stressors (such as hypoxia); whether any stress response could be blocked by clinically used doses of fentanyl; and whether fentanyl alone had any potentially deleterious physiologic effects in the fetus.

Offspring Produced from Heterotopic Ovarian Allografts in Male and Female Recipient Mice

Reproduction (Cambridge, England). Jun, 2004  |  Pubmed ID: 15175505

Studies on human ovarian xenografts and mouse allografts indicate that the male hormonal milieu and exogenous gonadotrophin administration stimulate antral follicle growth. However, it is not known whether oocytes produced under these conditions are developmentally competent. The objective of our study was to evaluate the developmental competence of oocytes produced in heterotopic mouse ovarian grafts placed in male and female recipient mice. Gonadotrophins were 7.5 IU pregnant mare serum gonadotrophin (PMSG) alone or 7.5 IU PMSG and 7.5 IU human chorionic gonadotrophin or were not given prior to oocyte collection. The developmental competence of oocytes was assessed by performing in vitro fertilisation and embryo transfer to recipients. When no gonadotrophins were given the cleavage rate was similar for oocytes collected from ovarian grafts in male and female recipients. Gonadotrophin treatment significantly (P < 0.05) increased two-cell formation by oocytes grown in female graft recipients but not in male recipients. Implantation rates, fetal development and the birth of live young were unaffected by the sex of the graft recipient or gonadotrophin treatment. Live offspring were produced from oocytes collected from ovarian grafts in male and female recipients treated with or without gonadotrophins. In conclusion, this work has shown that the hormonal environment of male mice can support the growth of oocytes in ovarian allografts and that these oocytes can produce live offspring.

Hypoxia Induced Activin Secretion by the Fetoplacental Unit: Differential Responses Related to Gestation

BJOG : an International Journal of Obstetrics and Gynaecology. Dec, 2004  |  Pubmed ID: 15663117

To determine whether activin A levels reflect oxygen availability in basal and hypoxic conditions in the late pregnant fetus and newborn lamb.

Melatonin Provides Neuroprotection in the Late-gestation Fetal Sheep Brain in Response to Umbilical Cord Occlusion

Developmental Neuroscience. Mar-Aug, 2005  |  Pubmed ID: 16046855

Oxygen free radicals, including the highly toxic hydroxyl radical (*OH), initiate lipid peroxidation and DNA/RNA fragmentation and damage cells. The pineal hormone melatonin is an antioxidant and powerful scavenger of *OH. We hypothesized that maternally administered melatonin could reduce *OH formation, lipid peroxidation, and DNA/RNA damage in the fetal brain in response to asphyxia. In 15 fetal sheep, extracellular *OH was measured by microdialysis in white and gray matter of the parasagittal cortex. In 10 fetuses, asphyxia was induced by umbilical cord occlusion for 10 min using an inflatable cuff - the ewes of these fetuses received either intravenous melatonin (1 mg bolus, then 1 mg/h for 2 h; n = 5) or vehicle (1% ethanol in saline; n = 5), and results were compared to fetuses with sham cord occlusion and vehicle-infused ewes (n = 5). Hypoxemia, acidemia, hypertension and bradycardia produced by cord occlusion was similar in the melatonin- and vehicle-treated groups. In the vehicle-treated group, cord occlusion resulted in a significant increase in *OH in gray matter at 8-9.5 h after occlusion (p < 0.05); in contrast, there was no *OH change in the melatonin-treated group. After cord occlusion, lipid peroxidation (4-hydroxynonenal immunoreactivity) found throughout the brain of vehicle-infused ewes was significantly less in the melatonin-infused group. Melatonin had no significant effect on the distribution of DNA/RNA fragmentation, as shown by 8-hydroxydeoxyguanosine immunoreactivity. Thus, brief asphyxia results in significant and delayed entry of *OH into the extracellular space of cortical gray matter in the fetal sheep brain, and melatonin given to the mother at the time of the insult abrogates this increase. Melatonin, in reducing O2 free radical production, may be an effective neuroprotective treatment for the fetus.

Detection of Morphological Changes of the Ovine Cervix in Response to Sex Steroids Using a Fluorescence Confocal Endomicroscope

American Journal of Obstetrics and Gynecology. Jan, 2006  |  Pubmed ID: 16389018

This study examined morphological changes of the ovine cervix in response to sex steroids using confocal microscopy.

Graft Site and Gonadotrophin Stimulation Influences the Number and Quality of Oocytes from Murine Ovarian Tissue Grafts

Reproduction (Cambridge, England). May, 2006  |  Pubmed ID: 16672350

Ovarian tissue cryopreservation and subsequent transplantation can restore fertility in cancer patients. This study used a mouse ovarian grafting model to investigate whether the graft site (bursal cavity, the kidney capsule or subcutaneous) influences the number, fertilization rate and developmental potential of oocytes recovered from grafts and whether using a standard gonadotrophin stimulation protocol would increase oocyte yield from the grafts. Mouse ovarian tissue was grafted into four week old mice and collected three weeks later. Graft recipients were treated either with or without exogenous gonadotrophin stimulation prior to graft collection. Grafted ovaries yielded oocytes that were either at the germinal vesicle (GV) stage or mature metaphase II (MII) stage at collection. These GV oocytes were matured before in vitro fertilization (IVF), while the MII oocytes underwent IVF immediately. Oocytes collected from the oviducts of non-grafted superovulated mice of the same age served as controls. Two-cell embryos were transferred to pseudopregnant recipients and recovered at day 15 of gestation or left to go to term. Graft retrieval and the number of oocytes from each graft were lowest from the subcutaneous graft site. The number of two-cell embryos produced was significantly higher for oocytes from the grafts to the bursa as compared with the other sites. All graft sites gave rise to embryos with comparable implantation rates and developmental potential to fetuses and offspring following transfer. However, the oocytes from grafted ovaries had a significantly lower developmental potential when compared with the control group. Stimulation with exogenous gonadotrophins did not significantly increase oocyte yield from grafted ovaries but did enhance oocyte maturation and development. In conclusion, graft site affects the number and quality of oocytes produced from ovarian grafts.

The Role of Corticosterone in Prehatch-induced Memory Deficits in Chicks

Brain Research. Dec, 2006  |  Pubmed ID: 17045973

We have previously shown that prehatch hypoxia (14% oxygen for 24 h), at E10 or E14 of chick embryonic development, produces significant memory deficits, with E10 hypoxia significantly affecting short-term memory and the subsequent formation of long-term memory, whereas E14 hypoxia only affects long-term memory. One of the consequences of hypoxia is the release of stress hormones and we found in this study that hypoxia at E10 or E14 induced a significant increase in circulating corticosterone immediately after the cessation of hypoxia (E11 and E15, respectively). Corticosterone levels remained significantly elevated at hatch in the E14 hypoxia group. This study describes the effect of a single, in ovo, injection of corticosterone on subsequent memory ability in hatched chicks. It was found that corticosterone (0.2 nmol/egg) at E10 or E14 mimicked the memory deficits produced by hypoxia at the same prehatch ages. Embryos treated with corticosterone at E10 had poor short-term memory at hatch, whereas corticosterone administration at E14 resulted in poor long-term memory. Embryos treated with corticosterone at E16 had raised circulating corticosterone levels at hatch, but did not have impaired memory. Treatment with corticosterone at E10, E12, E14 and E16 produced the same cognitive outcomes as hypoxia at the same prehatch ages. However, elevated plasma corticosterone levels at hatch did not necessarily cause the impaired memory processing. Raised levels were observed after treatment at E14 when memory processing was impaired, at E16 when memory was not impaired and not at E10 when memory was impaired. This suggests that an acute rather than sustained increase in plasma corticosterone at particular developmental ages is the cause of impaired memory processing seen at hatch.

The Effects of Maternal Betamethasone Administration on the Intrauterine Growth-restricted Fetus

Endocrinology. Mar, 2007  |  Pubmed ID: 17158204

Intrauterine growth restriction (IUGR) is associated with altered fetal cardiovascular function to ensure adequate perfusion of essential organs. IUGR fetuses are at risk of preterm delivery and so are likely to receive antenatal glucocorticoids to promote lung maturation. Because glucocorticoids alter vascular tone, we questioned whether such treatment may induce fetal cardiovascular alterations. Using pregnant sheep carrying twins, we induced IUGR at approximately 0.7 gestation by single umbilical artery ligation in one twin, using the other twin as a control. In each fetus, we monitored carotid blood flow and arterial blood gases. We administered 11.4 mg betamethasone (n = 5) or vehicle (n = 4) to the ewe on d 5 (BM1) and 6 (BM2) postsurgery. On d 7, fetal brains were collected for immunohistochemistry. In control fetuses, carotid blood flow decreased 3.5 h post-BM1 by 24% (P < 0.001), returning to baseline at 5.5 h. In IUGR fetuses, carotid flow decreased 2.5 h post-BM1 by 27% and then increased by 25% over baseline, peaking at 11 h (P < 0.001). Compared to control + saline, we observed a significant increase in oxidative damage (4-hydroxynonenal-positive cells) in the fetal hippocampus and subcallosal area of all treatment groups (IUGR + BM > IUGR + saline = control + BM). There was a significant correlation between carotid blood flow reperfusion after betamethasone and the number of 4-hydroxynonenal-positive cells in the cortex and hippocampus. These data suggest that antenatal betamethasone may induce brain injury in the IUGR fetus but not in the normally grown fetus.

The Effect of Hypoxia at Different Embryonic Ages on Impairment of Memory Ability in Chicks

International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience. Feb, 2008  |  Pubmed ID: 17904781

Hypoxia during the prenatal period is a principal antecedent to cognitive impairment after birth. In this study we have investigated the duration, severity and timing of acute hypoxia during chick embryonic development to elucidate the relative importance of these factors. Our results show that 24h of hypoxia (exposure to 14% oxygen) at embryonic day 10 (E10) results in significant impairment of intermediate and long-term memory in the post-hatch chick, which is the same as we observed with 4 days of hypoxia. At E14, 24h of hypoxia, 5min of anoxia, but not 1h of hypoxia, resulted only in impaired long-term memory; the same as 4 days of hypoxia from E14. Corticosterone levels, measured post-hatch as an indicator of a stress response, were significantly elevated in response to E10 hypoxia, and E14 hypoxia (both 1 and 24h) and anoxia. In a separate experiment we exposed embryos to 24h of hypoxia from E6 to E16, and found that memory deficits resulted from hypoxia at E9 and E10, and E13-E15, while corticosterone concentrations at hatch were significantly raised following E10-E16 hypoxia. These results demonstrate that the developmental age when the insult occurs determines the nature of the cognitive deficit and, if the severity of the insult is sufficient, then the outcome, or deficits in memory ability, are consistent whether the insult is acute or chronic. Importantly, there are two critical stages in development, which in the chick are around E10 and E14, when acute hypoxia results in significant adverse cognitive effects after hatch. These time-points correspond to two different stages in growth and development.

Gene Expression Profiling of Human Oocytes Following in Vivo or in Vitro Maturation

Human Reproduction (Oxford, England). May, 2008  |  Pubmed ID: 18346995

Immature human oocytes matured in vitro, particularly those from gonadotrophin stimulated ovaries, are developmentally incompetent when compared with oocytes matured in vivo. This developmental incompetence has been explained as poor oocyte cytoplasmic maturation without any determination of the likely molecular basis of this observation.

Application of Clinical Indices of Fetal Growth and Wellbeing to a Novel Laboratory Species, the Spiny Mouse

Reproductive Biology. Nov, 2008  |  Pubmed ID: 19092985

Ultrasound was used to measure growth of the spiny mouse fetus throughout gestation and to record Doppler measurements of heart rate and umbilical blood flow to monitor fetal blood supply and wellbeing. Female spiny mice were anesthetized on 6 occasions throughout pregnancy. Ultrasound was performed with a Philips HDI 5000 machine using a compact linear CL15-7 transducer. Fetal heart rate and growth parameters increased across gestation. Blood flow through the umbilical artery and vein showed increasing velocity over gestation, and reduced resistance index. Blood flow through the ductus venosus also increased in velocity over gestation; however the resistance index remained constant. We have determined changes in umbilical blood flow throughout pregnancy in the spiny mouse, which resemble those seen in human pregnancy. We also confirm that ultrasound can be used as a valuable, non-invasive technique for measuring fetal growth and wellbeing in the spiny mouse.

Cardiovascular Responses to Maternal Betamethasone Administration in the Intrauterine Growth-restricted Ovine Fetus

American Journal of Obstetrics and Gynecology. Dec, 2009  |  Pubmed ID: 19766978

The objective was to characterize the effect of glucocorticoid treatment on fetal organ blood flow and regional cerebral blood flow in normally grown fetuses and fetuses with intrauterine fetal growth restriction (IUGR).

Chondrogenic Differentiation of Adipose-derived Stem Cells

ANZ Journal of Surgery. Nov, 2009  |  Pubmed ID: 20078544

The Effects of Sildenafil Citrate (Viagra) on Uterine Blood Flow and Well Being in the Intrauterine Growth-restricted Fetus

American Journal of Obstetrics and Gynecology. Jan, 2009  |  Pubmed ID: 18845296

This study examined whether the type-5 phosphodiesterase inhibitor sildenafil citrate (Viagra; Pfizer, New York, NY) could increase uterine blood flow in intrauterine growth restriction (IUGR), thereby improving fetal oxygenation and well being.

Amnion Epithelial Cell Isolation and Characterization for Clinical Use

Current Protocols in Stem Cell Biology. Apr, 2010  |  Pubmed ID: 20373516

Human amnion epithelial cells (hAECs) are a heterologous population positive for stem cell markers; they display multilineage differentiation potential, differentiating into cells of the endoderm (liver, lung epithelium), mesoderm (bone, fat), and ectoderm (neural cells). They have a low immunogenic profile and possess potent immunosuppressive properties. Hence, hAECs may be a valuable source of cells for cell therapy. This unit describes an efficient and effective method of hAEC isolation, culture, and cryopreservation that is animal product-free and in accordance with current guidelines on preparation of cells for clinical use. Cells isolated using this method were characterized after 5 passages by analysis of karyotype, cell cycle distribution, and changes in telomere length. The differentiation potential of hAECs isolated using this animal product-free method was demonstrated by differentiation into lineages of the three primary germ layers and expression of lineage-specific markers analyzed by PCR, immunocytochemistry, and histology.

Cervical Motion Preservation Using Mesenchymal Progenitor Cells and Pentosan Polysulfate, a Novel Chondrogenic Agent: Preliminary Study in an Ovine Model

Neurosurgical Focus. Jun, 2010  |  Pubmed ID: 20521963

There is an unmet need for a procedure that could generate a biological disc substitute while at the same time preserving the normal surgical practice of achieving anterior cervical decompression. The objective of the present study was to test the hypothesis that adult allogeneic mesenchymal progenitor cells (MPCs) formulated with a chondrogenic agent could synthesize a cartilaginous matrix when implanted into a biodegradable carrier and cage, and over time, might serve as a dynamic interbody spacer following anterior cervical discectomy (ACD).

Human Amnion Epithelial Cell Transplantation Abrogates Lung Fibrosis and Augments Repair

American Journal of Respiratory and Critical Care Medicine. Sep, 2010  |  Pubmed ID: 20522792

Chronic lung disease characterized by loss of lung tissue, inflammation, and fibrosis represents a major global health burden. Cellular therapies that could restore pneumocytes and reduce inflammation and fibrosis would be a major advance in management.

Potential Applications for Using Stem Cells in Spine Surgery

Current Stem Cell Research & Therapy. Dec, 2010  |  Pubmed ID: 20528753

While the use of biologics as adjuncts for spine surgery is growing annually stem cells have yet to be approved for this clinical application. Stem cells have the unique ability to differentiate into a variety of musculoskeletal tissues including bone or cartilage. Moreover they have been shown to secrete growth factors that promote matrix repair and regeneration and can down regulate inflammation and immune cell functions. It is these combined activities that make stem cells attractive candidates for advancing current techniques in spine surgery and possibly mitigating those pathologies responsible for tissue degeneration and failure thereby minimising the need for surgical intervention at a later date. This review focuses on the characteristics of progenitor cells from different sources and explores their potential as adjuncts for both current and future applications in spine surgery. Where possible we draw on the experimental outcomes from our own preclinical studies using adult mesenchymal progenitor stem cells, as well as related studies by others to support our contention that stem cell based therapies will play a significant role in spine surgery in the future.

Reprogramming Factors Involved in Hybrids and Cybrids of Human Embryonic Stem Cells Fused with Hepatocytes

Cellular Reprogramming. Oct, 2010  |  Pubmed ID: 20936904

Embryonic stem cells (ESCs) have the potential to reprogram somatic cells into ESC-like cells through cell fusion. In the present study, the potential of human (h)ESC cytoplasts and karyoplasts to reprogram human hepatocytes was evaluated. Green fluorescent protein (GFP) transfected hESCs (ENVY cells) were fused with SNARF-1 (CellTracker)-labeled human hepatocytes using polyethylene glycol (PEG) and fluorescence-activated cell sorting (FACS) to produce hESC-hepatocyte hybrids. Immunocytochemical analysis of ESC markers showed that the hybrids expressed OCT4, TRA-1-60, TRA-1-81, SSEA-4, and GCTM-2. However, SSEA-1, which is typically low or absent on hESCs, was detected on hESC–hepatocyte hybrids. Moreover, reverse transcriptase polymerase chain reaction (RT-PCR) showed that alpha-fetoprotein, which is highly expressed in hepatocytes, was erased in the hybrids. These results indicated that hESCs have the potential to reprogram hepatocyte phenotype to a relatively undifferentiated state, but such hybrid cells are not identical to hESCs. Although hESC–hepatocyte hybrids were aneuploid, they were able to differentiate into embryoid bodies and some types of somatic cells. Furthermore, cybrids of enucleated hESCs and hepatocytes were produced by cell fusion, but the cybrids were unable to self-renew in the same way as hESCs. Presumably, the reprogramming factors are associated with the karyoplast and not the cytoplast of hESCs.

Human Amnion Epithelial Cells Prevent Bleomycin-induced Lung Injury and Preserve Lung Function

Cell Transplantation. 2011  |  Pubmed ID: 21092408

Human amnion epithelial cells (hAECs) have attracted recent attention as a promising source of cells for regenerative therapies, with reports that cells derived from human term amnion possess multipotent differentiation ability, low immunogenicity, and anti-inflammatory properties. Specifically, in animal models of lung disease characterized by significant loss of lung tissue secondary to chronic inflammation and fibrosis, the transplantation of hAECs has been shown to reduce both inflammation and subsequent fibrosis. To further explore the mechanisms by which hAECs reduce pulmonary fibrosis and enhance lung regeneration, we utilized a bleomycin-induced model of pulmonary fibrosis and investigated the ability of hAECs to reduce fibrosis and thereby improve pulmonary function. We aimed to determine if hAECs, injected into the peritoneal cavity could migrate to the lung, engraft, and form functional lung epithelium, and whether hAECs could modulate the inflammatory environment in the bleomycin-injured lung. We demonstrated that, compared to bleomycin alone, IP administration of hAECs 24 h after bleomcyin, decreased gene expression of the proinflammatory cytokines TNF-α, TGF-β, IFN-γ, and IL-6 and decreased subsequent pulmonary fibrosis with less pulmonary collagen deposition, reduced levels of α-smooth muscle actin and decreased inflammatory cell infiltrate. We also showed that hAECs are able to prevent a decline in pulmonary function associated with bleomycin-induced lung damage. We were unable to detect any significant engraftment of hAECs in injured, or uninjured, lung after administration. The findings from this study support the further investigation of hAECs as a potential cell therapy for inflammatory and fibrogenic diseases.

Cervical Interbody Fusion is Enhanced by Allogeneic Mesenchymal Precursor Cells in an Ovine Model

Spine. Apr, 2011  |  Pubmed ID: 21192297

An experimental study using a sheep cervical spine interbody fusion model.

Anti-inflammatory Therapy in an Ovine Model of Fetal Hypoxia Induced by Single Umbilical Artery Ligation

Reproduction, Fertility, and Development. 2011  |  Pubmed ID: 21211468

Perinatal morbidity and mortality are significantly higher in pregnancies complicated by chronic hypoxia and intrauterine growth restriction (IUGR). Clinically, placental insufficiency and IUGR are strongly associated with a fetoplacental inflammatory response. To explore this further, hypoxia was induced in one fetus in twin-bearing pregnant sheep (n=9) by performing single umbilical artery ligation (SUAL) at 110 days gestation. Five ewes were administered the anti-inflammatory drug sulfasalazine (SSZ) daily, beginning 24h before surgery. Fetal blood gases and inflammatory markers were examined. In both SSZ- and placebo-treated ewes, SUAL fetuses were hypoxic and growth-restricted at 1 week (P<0.05). A fetoplacental inflammatory response was observed in SUAL pregnancies, with elevated pro-inflammatory cytokines, activin A and prostaglandin E(2). SSZ did not mitigate this inflammatory response. It is concluded that SUAL induces fetal hypoxia and a fetoplacental inflammatory response and that SSZ does not improve oxygenation or reduce inflammation. Further studies to explore whether alternative anti-inflammatory treatments may improve IUGR outcomes are warranted.

A Comparison of Mesenchymal Precursor Cells and Amnion Epithelial Cells for Enhancing Cervical Interbody Fusion in an Ovine Model

Neurosurgery. Apr, 2011  |  Pubmed ID: 21242823

Rapid, reliable fusion is the goal in anterior cervical diskectomy and fusion. Iliac crest autograft has a high rate of donor-site morbidity. Alternatives such as bone graft substitutes lack osteoinductivity, and recombinant bone morphogenetic proteins risk life-threatening complications. Both allogeneic mesenchymal precursor cells (MPCs) and amnion derived epithelial cells (AECs) have osteogenic potential.

Assessment of Respiratory Physiology of C57BL/6 Mice Following Bleomycin Administration Using Barometric Plethysmography

Respiration; International Review of Thoracic Diseases. Oct, 2011  |  Pubmed ID: 21997573

Background: Assessment of deterioration of lung function in animal models of respiratory disease traditionally relies upon quantitating biochemical markers. Plethysmography is a technique for measuring lung function that includes invasive and non-invasive methodologies. Objectives: This study used whole-body barometric plethysmography to characterize change(s) in respiratory physiology of C57BL/6 mice following bleomycin administration. Methods: Cohorts of animals were culled at 3, 7, 14 and 28 days to semi-quantitatively score the lung for fibrosis, and quantitate levels of hydroxyproline in the lung. We have described in detail the response of C57BL/6 mice to bleomycin. Results: Bleomycin-treated mice had reduced minute volume (p < 0.05) and an increased total breathing cycle time (p < 0.0001), which consisted of a shortened inspiration time (p < 0.01) and an extended expiration time (p < 0.0001). Conclusions: We have demonstrated that plethysmography can be a primary indicator of the development of respiratory disease in the mouse and would thus be suitable in assessing potential therapies since any truly effective treatment should elicit restoration of respiratory parameters in addition to improving traditional biochemical and histological indices of lung function.

The Effects of Intrauterine Growth Restriction and Antenatal Glucocorticoids on Ovine Fetal Lung Development

Pediatric Research. Feb, 2012  |  Pubmed ID: 22337223

Intrauterine fetal growth restriction (IUGR) is associated with high rates of neonatal morbidity. IUGR babies are often born preterm and are therefore exposed to antenatal glucocorticoids. Antenatal glucocorticoids significantly improve overall survival rates of preterm infants, but there is a paucity of information about their effects on IUGR infants. We induced IUGR in sheep by single umbilical artery ligation (SUAL), or sham in control fetuses. To half the ewes, we administered betamethasone (BM) on days 5 (BM1) and 6 (BM2) following surgery and collected fetal lung tissue on day 7. SUAL alone was associated with higher circulating fetal cortisol levels (2.8±0.4 vs 1.0±0.4, P=0.001) compared to controls, but no changes in lung morphology or surfactant protein (SP) gene expression. BM was associated with a significant reduction in lung tissue density (P=0.048). There were no significant differences between groups in lung DNA concentration or septal crest density. SP-A, -B and -C gene expression was significantly increased in control and SUAL fetuses given BM. These results show that in SUAL fetuses, maternal betamethasone is associated with acceleration of fetal lung structure, as occurs in normally grown fetuses, and that betamethasone induces SP production, an effect not observed in SUAL-induced IUGR fetuses alone.