Michael House

Tufts University, Medford, MA, United States

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Publications (55)127.9 Total impact

  • Helen Feltovich, Michael House
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    ABSTRACT: A multitude of pathophysiologic pathways culminate in the final common denominator of cervical softening, shortening, and dilation that lead to preterm birth. At present, a variety of emerging technology aims to objectively quantify critical cervical parameters such as microstructural organization and softening of the cervix. If the nature and timing of cervical changes can be precisely identified, it should be possible to identify the causative upstream molecular processes and resultant biomechanical events associated with each unique pathway. This would promote molecular studies, ultimately leading to novel approaches to preterm birth prediction, novel treatments, and prevention.
    Clinical obstetrics and gynecology. 09/2014; 57(3):531-6.
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    ABSTRACT: Objective:To evaluate the biocompatibility of silk gel for cervical injection.Study Design:Silk gel was injected into the cervix of pregnant rats on day 13 (n = 11) and harvested at day 17. Histology of silk gel was compared with suture controls. Also, human cervical fibroblasts were cultured on silk gel and tissue culture plastic (TCP) in vitro. Cell viability, proliferation, metabolic activity, gene expression (COL1A1, COL3A1, and COX2), and release of proinflammatory mediators (interleukin [IL] 6 and IL-8) were evaluated.Results:In vivo, a mild foreign body response was seen surrounding the silk gel and suture controls. In vitro, cervical fibroblasts were viable, metabolically active, and proliferating at 72 hours. Release of IL-6 and IL-8 was similar on silk gel and TCP. Collagen and COX2 gene expression was similar or slightly decreased compared with TCP.Conclusions:Silk gel was well tolerated in vivo and in vitro, which supports continuing efforts to develop silk gels as an alternative to cervical cerclage.
    Reproductive sciences (Thousand Oaks, Calif.) 02/2014; · 2.31 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2014; 210(1):S348. · 3.88 Impact Factor
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    ABSTRACT: Progesterone supplementation is recommended to prevent preterm birth in women with a short cervix, but the mechanism is unclear. We hypothesize that progesterone acts by altering the composition of cervical extracellular matrix (ECM). We tested this hypothesis using human cervical fibroblasts in both two-dimensional (2D) and three-dimensional (3D) culture. For 2D culture, cells were seeded in six well plates and cultured with media supplemented with estradiol (10(-8) M), progesterone (10(-7) M, 10(-6) M) and vehicle. For 3D culture, cells were cultured on a porous silk protein scaffold system. Progesterone and estrogen receptors were documented by immunohistochemistry and Western blot. In both 2D and 3D culture, decreased collagen synthesis was seen with increased progesterone concentration. 3D cultures could be maintained significantly longer than 2D cultures and the morphology of 3D cultures appeared similar to native cervical tissue. Thus, further studies were performed in 3D culture. To determine the effect of progesterone concentration, 3D scaffolds were cultured with estradiol (10(-8) M) and five progesterone conditions: vehicle, 10(-9) M, 10(-8) M, 10(-7) M and 10(-7) M + 10(-6) M mifepristone. The highest progesterone concentration correlated with the least amount of collagen synthesis. Collagen synthesis progressively increased as progesterone concentration decreased. This effect was partially antagonized by mifepristone, suggesting the mechanism is mediated by the progesterone receptor. This hormonally-responsive 3D culture system supports the hypothesis that progesterone has a direct effect on remodeling cervical ECM during pregnancy. The 3D culture system could be useful for studying the mechanism of progesterone effects on the cervix.
    Biology of Reproduction 11/2013; · 4.03 Impact Factor
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    ABSTRACT: Globally, an estimated 13 million preterm babies are born each year. These babies are at increased risk of infant mortality and life-long health complications. Interventions to prevent preterm birth (PTB) require an understanding of processes driving parturition. Prostaglandins (PGs) have diverse functions in parturition, including regulation of uterine contractility and tissue remodeling. Our studies on cervical remodeling in mice suggest that although local synthesis of PGs are not increased in term ripening, transcripts encoding PG-endoperoxide synthase 2 (Ptgs2) are induced in lipopolysaccharide (LPS)-mediated premature ripening. This study provides evidence for two distinct pathways of cervical ripening: one dependent on PGs derived from paracrine or endocrine sources and the other independent of PG actions. Cervical PG levels are increased in LPS-treated mice, a model of infection-mediated PTB, consistent with increases in PG synthesizing enzymes and reduction in PG-metabolizing enzymes. Administration of SC-236, a PTGS2 inhibitor, along with LPS attenuated cervical softening, consistent with the essential role of PGs in LPS-induced ripening. In contrast, during term and preterm ripening mediated by the antiprogestin, mifepristone, cervical PG levels, and expression of PG synthetic and catabolic enzymes did not change in a manner that supports a role for PGs. These findings in mice, supported by correlative studies in women, suggest PGs do not regulate all aspects of the parturition process. Additionally, it suggests a need to refocus current strategies toward developing therapies for the prevention of PTB that target early, pathway-specific processes rather than focusing on common late end point mediators of PTB.
    Endocrinology 11/2013; · 4.72 Impact Factor
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    ABSTRACT: Ascending infection from the colonized vagina to the normally sterile intrauterine cavity is a well-documented cause of preterm birth. The primary physical barrier to microbial ascension is the cervical canal, which is filled with a dense and protective mucus plug. Despite its central role in separating the vaginal from the intrauterine tract, the barrier properties of cervical mucus have not been studied in preterm birth. To study the protective function of the cervical mucus in preterm birth we performed a pilot case-control study to measure the viscoelasticity and permeability properties of mucus obtained from pregnant women at high-risk and low-risk for preterm birth. Using extensional and shear rheology we found that cervical mucus from women at high-risk for preterm birth was more extensible and forms significantly weaker gels compared to cervical mucus from women at low-risk of preterm birth. Moreover, permeability measurements using fluorescent microbeads show that high-risk mucus was more permeable compared with low-risk mucus. Our findings suggest that critical biophysical barrier properties of cervical mucus in women at high-risk for preterm birth are compromised compared to women with healthy pregnancy. We hypothesize that impaired barrier properties of cervical mucus could contribute to increased rates of intrauterine infection seen in women with preterm birth. We furthermore suggest that a robust association of spinnbarkeit and preterm birth could be an effectively exploited biomarker for preterm birth prediction.
    PLoS ONE 01/2013; 8(8):e69528. · 3.53 Impact Factor
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    ABSTRACT: Objective:New therapies to prevent preterm birth are needed. Our objective was to study an injectable biomaterial for human cervical tissue as an alternative to cervical cerclage.Study Design:Human cervical tissue specimens were obtained from premenopausal gynecological hysterectomies for benign indications. A 3-part biomaterial was formulated, consisting of silk protein solution blended with a 2-part polyethylene glycol gelation system. The solutions were injected into cervical tissue and the tissue was evaluated for mechanical properties, swelling, cytocompatibility, and histology.Results:The stiffness of cervical tissue more than doubled after injection (P = .02). Swelling properties of injected tissue were no different than native tissue controls. Cervical fibroblasts remained viable for at least 48 hours when cultured on the biomaterial.Conclusions:We report a silk-based, biocompatible, injectable biomaterial that increased the stiffness of cervical tissue compared to uninjected controls. Animal studies are needed to assess this biomaterial in vivo.
    Reproductive sciences (Thousand Oaks, Calif.) 12/2012; · 2.31 Impact Factor
  • Michael House, Reid McCabe, Simona Socrate
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    ABSTRACT: Preterm birth affects over 12% of all pregnancies in the United States for an annual healthcare cost of $26 billion. Preterm birth is a multifactorial disorder but cervical abnormalities are a prominent feature in many patients. Women with a short cervix are known to be at increased risk for preterm birth and a short cervix is used to target therapy to prevent preterm birth. Although the clinical significance of a short cervix is well known, the three-dimensional anatomical changes that lead to cervical shortening are poorly understood. Here, we review our previous studies of the three-dimensional anatomy of the cervix and uterus during pregnancy. The rationale for these studies was to improve our understanding of the deformation mechanisms leading to cervical shortening. Both magnetic resonance imaging and three-dimensional (3D) ultrasound were used to obtain anatomical data in healthy, pregnant volunteers. Solid models were constructed from the 3D imaging data. These solid models were used to create numerical models suitable for biomechanical simulation. Three simulations were studied: cervical funneling, uterine growth, and fundal pressure. These simulations showed that cervical changes are a complex function of the tissue properties of the cervical stroma, the loading conditions associated with pregnancy and the 3D anatomical geometry of the cervix and surrounding structures. An improved understanding of these cervical changes could point to new approaches to prevent undesired cervical shortening. This new insight should lead to therapeutic strategies to delay or prevent preterm birth. Clin. Anat., 2012. © 2012 Wiley Periodicals, Inc.
    Clinical Anatomy 11/2012; · 1.16 Impact Factor
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    ABSTRACT: Objectives- The purpose of this study was to determine whether sonographic formulas for estimating fetal weight are as accurate for fetuses affected with gastroschisis as they are for healthy fetuses. We hypothesized that because the most commonly used Hadlock formulas rely on the abdominal circumference as a biometric variable, estimates of birth weight are less reliable in fetuses with gastroschisis than in healthy fetuses. Methods- We performed a chart review of all fetuses with a prenatal diagnosis of gastroschisis at 3 tertiary care institutions from 1990 to 2008. Charts were reviewed for clinical and sonographic data. The estimated fetal weight at the prenatal sonogram closest to delivery was compared to the birth weight. Published Hadlock formulas using 4 biometric parameters were used to calculate the estimated fetal weight. Data analysis was performed using the Student t test and χ(2) test for continuous and categorical variables, respectively. Results- One hundred eleven patients with gastroschisis were identified. Sixty-six patients had a prenatal sonogram with a calculated estimated fetal weight within 7 days of delivery; 88 patients had a sonogram within 14 days. The mean birth weights ± SD were 2292 ± 559 and 2477 ± 531 g in the 0- to 7- and 8- to 14-day groups, respectively. Sonographic biometric measurements underestimated the birth weight by an average of 5.6%. Intrauterine growth restriction was predicted in 72% of all pregnancies but was only present in 52%. Conclusions- Our study shows a systematic error of birth weight underestimation when using the Hadlock formulas in fetuses affected with gastroschisis.
    Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 11/2012; 31(11):1753-8. · 1.40 Impact Factor
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    ABSTRACT: To estimate the relationship between nuchal translucency thickness and abnormal karyotype, major congenital anomaly, perinatal loss, and composite abnormal outcome in fetuses with first-trimester nuchal cystic hygroma. We performed a retrospective cohort study of first-trimester fetuses with ultrasound-diagnosed nuchal cystic hygroma collected over a 10-year period. There were 944 first-trimester fetuses with nuchal cystic hygroma. A karyotype abnormality occurred in 54.9% (400 of 729) of fetuses. A major congenital anomaly occurred in 28.8% (61 of 212) of fetuses with a normal karyotype. Perinatal loss occurred in 39% (115 of 295) of fetuses not electively terminated. Overall, an abnormal outcome occurred in 86.6% (543 of 627) of fetuses. After adjusting for potential confounders, every 1-mm increase in nuchal translucency thickness increased the odds of an abnormal karyotype by 44% (adjusted odds ratio [OR] 1.44, 95% confidence interval [CI] 1.29-1.60, P<.001), the odds of major congenital anomaly by 26% (adjusted OR 1.26, 95% CI, 1.08-1.47, P=.003), the odds of perinatal loss by 47% (adjusted OR 1.47, 95% CI 1.07-2.02, P=.019), and the odds of a composite abnormal outcome by 77% (adjusted OR 1.77, 95% CI 1.15-2.74, P=.01). First-trimester nuchal cystic hygroma is associated with high rates of karyotype abnormality, major congenital anomaly, perinatal loss, and abnormal outcome. As the thickness of the nuchal translucency increases, the odds of abnormal karyotype, major congenital anomaly, perinatal loss, and abnormal outcome increase.
    Obstetrics and Gynecology 08/2012; 120(3):551-9. · 4.80 Impact Factor
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    ABSTRACT: To develop a prototype electronic ruler for assessment of fetal heart rate (FHR) variability on an electronic monitor and test its reliability and accuracy. A prototype electronic ruler was designed and developed for assessment of FHR variability on electronic monitors. The electronic ruler consisted of horizontal bands that were sized and colored to embed the four FHR variability categories. The reliability and accuracy of using the electronic ruler to assess FHR variability was studied with expert clinicians. Intrarater and interrater reliability was moderate for both the electronic ruler and paper strips. The amplitude measurement accuracy of expert variability assessment compared with a gold standard was significantly improved (p < 0.001) with the electronic ruler versus paper strips. The accuracy of subjects' FHR variability category responses compared with the gold standard revealed no significant difference (p = 0.50) using either display type. Performance of the electronic ruler was equivalent to paper strips, which may aid assessment of variability on electronic monitors as paper strips become less prevalent.
    American Journal of Perinatology 03/2012; 29(6):409-13. · 1.57 Impact Factor
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    ABSTRACT: Objective Cervical ripening is associated with infiltration of inflammatory cells into the cervical stroma. However, the mechanism is poorly understood. We hypothesized cell stretch could lead to increased production of pro-inflammatory cytokines (IL-6, IL-8). We tested this hypothesis with cervical fibroblasts in 2D and 3D culture.
    SMFM Annual Meeting; 01/2012
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    ABSTRACT: Cervical shortening and cervical insufficiency contribute to a significant number of preterm births. However, the deformation mechanisms that control how the cervix changes its shape from long and closed to short and dilated are not clear. Investigation of the biomechanical problem is limited by (1) lack of thorough characterization of the three-dimensional anatomical changes associated with cervical deformation and (2) difficulty measuring cervical tissue properties in vivo. The objective of the present study was to explore the feasibility of using three-dimensional ultrasound and fundal pressure to obtain anatomically-accurate numerical models of large-strain cervical deformation during pregnancy and enable noninvasive assessment of cervical-tissue compliance. Healthy subjects (n = 6) and one subject with acute cervical insufficiency in the midtrimester were studied. Extended field-of-view ultrasound images were obtained of the entire uterus and cervix. These images aided construction of anatomically accurate numerical models. Cervical loading was achieved with fundal pressure, which was quantified with a vaginal pressure catheter. In one subject, the anatomical response to fundal pressure was matched by a model-based simulation of the deformation response, thereby deriving the corresponding cervical mechanical properties and showing the feasibility of noninvasive assessment of compliance. The results of this pilot study demonstrate the feasibility of a biomechanical modeling framework for estimating cervical mechanical properties in vivo. An improved understanding of cervical biomechanical function will clarify the pathophysiology of cervical shortening.
    Ultrasonic Imaging 01/2012; 34(1):1-14. · 1.58 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2012; 206(1):S207. · 3.88 Impact Factor
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    ABSTRACT: Cervical dysfunction contributes to a significant number of preterm births and is a common cause of morbidity and mortality in newborn infants. Cervical dysfunction is related to weakened load bearing properties of the collagen-rich cervical stroma. However, the mechanisms responsible for cervical collagen changes during pregnancy are not well defined. It is known that blood flow and oxygen tension significantly increase in reproductive tissues during pregnancy. To examine the effect of oxygen tension, a key mediator of tissue homeostasis, on the formation of cervical-like tissue in vitro, we grew primary human cervical cells in both two-dimensional (2D) and three-dimensional (3D) culture systems at 5% and 20% oxygen. Immunofluorescence studies revealed a stable fibroblast phenotype across six passages in all subjects studied (n=5). In 2D culture for 2 weeks, 20% oxygen was associated with significantly increased collagen gene expression (p<0.01), increased tissue wet weight (p<0.01), and increased collagen concentration (p=0.046). 3D cultures could be followed for significantly longer time frames than 2D cultures (12 weeks vs. 2 weeks). In contrast to 2D cultures, 20% oxygen in 3D cultures was associated with decreased collagen concentration (p<0.01) and unchanged collagen gene expression, which is similar to cervical collagen changes seen during pregnancy. We infer that 3D culture is more relevant for studying cervical collagen changes in vitro. The data suggest that increased oxygen tension may be related to significant cervical collagen changes seen in pregnancy.
    Tissue Engineering Part A 09/2011; 18(5-6):499-507. · 4.64 Impact Factor
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    ABSTRACT: The purpose of this study was to use a fixed reference to study movement (displacement) of the cervical internal os from the second to the third trimester in singletons and twins. The rationale was to gain insight into anatomic changes associated with cervical shortening. For each patient, 2 transperineal scans were performed 12 weeks apart (20 and 32 weeks). The internal os and symphysis pubis were visualized in the same field of view. Image registration techniques were used to align the 2 scans using the symphysis as a fixed reference. Total displacement, anterior displacement, and inferior displacement of the internal os were measured. Displacements were correlated with cervical shortening. Bland-Altman plots and interobserver intraclass correlation coefficients were calculated. A total of 42 healthy participants were studied: 28 with singletons and 14 with twins. The mean ± SD values for total displacement were 2.1 ± 1.2 and 2.0 ± 1.2 cm for singletons and twins, respectively (P = .75). The direction of displacement was significantly different. The mean anterior displacement was 1.1 cm greater for singletons than for twins (95% confidence interval, 0.29-2.0 cm, P = .01). Mean inferior displacement was 1.3 cm greater for twins than for singletons (95% confidence interval, 2.2-0.1 cm; P = .03). Only inferior displacement correlated with cervical shortening (P < .001; R(2) = 0.74). For every 2.2 cm of inferior displacement, the cervix shortened 1.0 cm. Assessments of reliability showed good agreement between 2 observers. The anatomic position of the internal cervical os depends on gestational age and fetal number. Cervical shortening correlated most strongly with inferior displacement.
    Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 09/2011; 30(9):1197-204. · 1.40 Impact Factor
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    ABSTRACT: To determine whether a vaginal-rectal culture obtained after antibiotic therapy has begun accurately detects pre-existing colonization with group B streptococcus (GBS). A prospective cohort study of women presenting at in labor who were known to be colonized with GBS were recruited. A GBS culture was obtained prior to administration of intravenous penicillin prophylaxis and repeated 2 hours following the first dose of penicillin. The two results were compared. Eighty subjects were recruited. Complete results were obtained for 61 (76 %) subjects. Of these, 47 (77 %) had a GBS positive on initial culture. Persistence of GBS 2 hours after antibiotic exposure was seen in 30/47 (64 %). Conversion from GBS positive to GBS negative status was seen in 17/47 (36%). A vaginal-rectal culture for GBS performed after antibiotic prophylaxis has commenced may not accurately reflect a patient's GBS colonization status.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 08/2011; 25(6):736-8. · 1.36 Impact Factor
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    ABSTRACT: Screening of biomaterial and tissue systems in vitro, for guidance of performance in vivo, remains a major requirement in the field of tissue engineering. It is critical to understand how culture stimulation affects both tissue construct maturation and function, with the goal of eliminating resource-intensive trial-and-error screening and better matching specifications for various in vivo needs. In this article a multifunctional and robust bioreactor design that addresses this need is presented. The design enables a range of mechanical inputs, durations, and frequencies to be applied in coordination with noninvasive optical assessments. A variety of biomaterial systems, including micro- and nano-fiber and porous sponge biomaterials, as well as cell-laden tissue engineering constructs were used in validation studies to demonstrate the versatility and utility of this new bioreactor design. The silk-based biomaterials highlighted in these studies offered several unique optical signatures for use in label-free nondestructive imaging that allowed for sequential profiling. Both short- and long-term culture studies were conducted to evaluate several practical scenarios of usage: on a short-term basis, the authors demonstrate that construct cellularity can be monitored by usage of nonpermanent dyes; on a more long-term basis, the authors show that cell ingrowth can be monitored by green-fluorescent protein (GFP)-labeling, and construct integrity probed with concurrent load/displacement data. The ability to nondestructively track cells, biomaterials, and new matrix formation without harvesting designated samples at each time point will lead to less resource-intensive studies and should enhance our understanding and the discovery of biomaterial designs related to functional tissue engineering.
    Annals of Biomedical Engineering 02/2011; 39(5):1390-402. · 3.23 Impact Factor
  • American Journal of Obstetrics and Gynecology - AMER J OBSTET GYNECOL. 01/2011; 204(1).
  • American Journal of Obstetrics and Gynecology 01/2011; 204(1). · 3.88 Impact Factor

Publication Stats

265 Citations
127.90 Total Impact Points

Institutions

  • 2005–2012
    • Tufts University
      • • Department of Mechanical Engineering
      • • Department of Biomedical Engineering
      • • Department of Obstetrics and Gynecology
      Medford, MA, United States
    • Tufts Medical Center
      • Department of Obstetrics and Gynecology
      Boston, Massachusetts, United States
  • 2010
    • The Ohio State University
      Columbus, Ohio, United States
  • 2009–2010
    • Massachusetts Institute of Technology
      • Department of Mechanical Engineering
      Cambridge, MA, United States