Sundeep G Keswani

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

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Publications (57)89.58 Total impact

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    ABSTRACT: The purpose of this study was to characterize the growth rate of sacrococcygeal teratomas (SCTs) and determine its relationship to adverse outcomes.
    Journal of pediatric surgery. 06/2014; 49(6):985-9.
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    ABSTRACT: Significance: Postnatal wounds heal with characteristic scar formation. In contrast, the mid-gestational fetus is capable of regenerative healing, which results in wound repair that is indistinguishable from uninjured skin. However, the underlying mechanisms of fetal regenerative phenotype are unknown. Recent Advances: The potent anti-inflammatory cytokine, interleukin-10 (IL-10), plays an essential role in the ability of the fetus to heal regeneratively and has been shown to recapitulate scarless healing in postnatal tissue. IL-10's ability to facilitate regenerative healing is likely a result of pleiotropic effects, through regulation of the inflammatory response, as well as novel roles as a regulator of the extracellular matrix, fibroblast cellular function, and endothelial progenitor cells. Overexpression of IL-10 using a variety of methods has been demonstrated to recapitulate the fetal regenerative phenotype in post-natal tissue, in conjunction with promising results of Phase II clinical trials using recombinant IL-10. Critical Issues: Successful wound healing is a complex process that requires coordination of multiple growth factors, cell types, and extracellular cellular matrix components. IL-10 has been demonstrated to be critical in the fetus' intrinsic ability to heal without scars, and, further, can induce scarless healing in postnatal tissue. The mechanisms through which IL-10 facilitates this regeneration are likely the result of IL-10's pleiotropic effects. Efforts to develop IL-10 as an anti-scarring agent have demonstrated promising results. Future Directions: Further studies on the delivery, including dose, route, and timing, are required in order to successfully translate these promising findings from in vitro studies and animal models into clinical practice. IL-10 holds significant potential as an anti-scarring therapeutic.
    Advances in wound care. 04/2014; 3(4):315-323.
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    ABSTRACT: Chronic wounds are characterized by a wound healing and neovascularization deficit. Strategies to increase neovascularization can significantly improve chronic wound healing. Insulin-like growth factor (IGF)-1 is reported to be a keratinocyte mitogen and is believed to induce angiogenesis via a vascular endothelial growth factor (VEGF)-dependent pathway. Using a novel ex vivo human dermal wound model and a diabetic-impaired wound healing murine model, we hypothesized that adenoviral overexpression of IGF-1 (Ad-IGF-1) will enhance wound healing and induce angiogenesis through a VEGF-dependent pathway. Ex vivo: 6-mm full-thickness punch biopsies were obtained from normal human skin, and 3-mm full-thickness wounds were created at the center. Skin explants were maintained at air liquid interface. Db/db murine model: 8-mm full-thickness dorsal wounds in diabetic (db/db) mice were created. Treatment groups in both human ex vivo and in vivo db/db wound models include 1 × 10(8) particle forming units of Ad-IGF-1 or Ad-LacZ, and phosphate buffered saline (n = 4-5/group). Cytotoxicity (lactate dehydrogenase) was quantified at days 3, 5, and 7 for the human ex vivo wound model. Epithelial gap closure (hematoxylin and eosin; Trichrome), VEGF expression (enzyme-linked immunosorbent assay), and capillary density (CD 31 + CAPS/HPF) were analyzed at day 7. In the human ex vivo organ culture, the adenoviral vectors did not demonstrate any significant difference in cytotoxicity compared with phosphate buffered saline. Ad-IGF-1 overexpression significantly increases basal keratinocyte migration, with no significant effect on epithelial gap closure. There was a significant increase in capillary density in the Ad-IGF-1 wounds. However, there was no effect on VEGF levels in Ad-IGF-1 samples compared with controls. In db/db wounds, Ad-IGF-1 overexpression significantly improves epithelial gap closure and granulation tissue with a dense cellular infiltrate compared with controls. Ad-IGF-1 also increases capillary density, again with no significant difference in VEGF levels in the wounds compared with control treatments. In two different models, our data demonstrate that adenoviral-mediated gene transfer of IGF-1 results in enhanced wound healing and induces angiogenesis via a VEGF-independent pathway. Understanding the underlying mechanisms of IGF-1 effects on angiogenesis may help produce novel therapeutics for chronic wounds or diseases characterized by a deficit in neovascularization.
    Journal of Surgical Research 03/2014; · 2.02 Impact Factor
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    ABSTRACT: Anti-inflammatory cytokine interleukin (IL)-10 has been shown to induce regenerative healing in postnatal wounds. A viral homolog of IL-10 produced by human cytomegalovirus (CMV IL-10) similarly generates potent immunoregulatory effects, but its effects on wound healing have not been investigated. Currently, there are limited cost-effective methods of screening vulnerary therapeutics. Taken together, we aim to develop and validate a novel human ex vivo dermal wound model and hypothesize that CMV IL-10 will enhance dermal wound healing. Full-thickness circular (6-mm) explants were taken from surgical skin samples and 3-mm full-thickness wounds were created. Explants were embedded in collagen I matrix and maintained in specially formulated media with the epidermis at air-liquid interface, and treated with human IL-10 or CMV IL-10 (200 ng/mL). The viability of cultured explants was validated by histology and lactate dehydrogenase (LDH) activity. Epithelial gap, epithelial height, basal keratinocyte migration, vascular endothelial growth factor levels, and neovascularization were measured at days 3 and 7 to determine IL-10 effects on wound healing. Culture explants at day 7 appeared similar to fresh skin in morphology, cell, and vessel density. By day 14, the epidermis separated from the dermis and the cell density diminished. Day 7 wounds appeared viable with advancing epithelial and basal keratinocyte migration with no evidence of necrosis. Cytotoxicity analysis via the quantification of LDH revealed no differences between controls and treated groups. There was a slight increase in the quantity of LDH in media at day 3; however, this decreased at day 5 and continued to decline up to day 21. CMV IL-10 treatment resulted in a significant decrease in the epithelial gap and an increase in epithelial height. There were no differences in the rates of basal keratinocyte migration at day 7 between treated and control groups. Interestingly, human IL-10 increased vascular endothelial growth factor expression and neovascularization compared with controls. The human ex vivo wound model provides a simple and viable design to study dermal wound healing. Both IL-10 homologs demonstrate vulnerary effects. The viral homolog demonstrates enhanced effects on wound closure compared with human IL-10. These data represent a novel tool that can be used to screen therapeutics, such as CMV IL-10, before preclinical studies.
    Journal of Surgical Research 02/2014; · 2.02 Impact Factor
  • Alice King, Sundeep G. Keswani
    Journal of Surgical Research 01/2014; 186(1):87–88. · 2.02 Impact Factor
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    ABSTRACT: Chylothorax is a frequent complication in congenital diaphragmatic hernia (CDH) infants and is associated with significant morbidity. The optimal treatment strategy remains unclear. We hypothesize that octreotide decreases chylous effusions in infants with CDH. This is a retrospective study of all infants with CDH admitted to our institution from October 2006 to October 2011. Eleven (12%) infants developed a chylothorax. Five infants were managed conservatively with thoracostomy and total parenteral nutrition. Six infants were started on octreotide therapy. None of the infants required surgical intervention to stop the effusion. There was no significant difference in survival to discharge, length of stay, or average daily chest tube output between groups. There appeared to be a temporally associated drop in chest tube output upon initiation of octreotide in two infants; however, the overall rate of decline in chest tube drainage was unchanged. In addition, there were infants in the conservative group who demonstrated a similar drop in daily chest tube output despite the absence of octreotide. Our data suggest that the majority of chylous effusions in CDH infants resolve with conservative therapy alone.
    Journal of Pediatric Surgery 11/2013; 48(11):2226-9. · 1.38 Impact Factor
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    ABSTRACT: In utero hematopoietic cellular transplantation (IUHCT) holds great promise for the treatment of congenital diseases of cellular dysfunction such as sickle cell disease, immunodeficiency disorders and inherited metabolic disorders. However, repeated failures in clinical cases of IUHCT that do not involve an immunodeficiency disease force a closer examination of the fetal immune system. While the mechanisms regulating T cell tolerance have been previously studied, the educational mechanisms leading to NK cell tolerance in prenatal chimeras remain unknown. As a low level of donor cells (1.8%) is required to induce and maintain this tolerance, it is likely that these mechanisms employ indirect host-donor interaction. This report examines donor-to-host MHC transfer (trogocytosis) as an intrinsic mechanism regulating the development and maintenance of NK cell tolerance in prenatal chimeras. The findings demonstrate that phenotypically tolerant host NK cells express low levels of transferred donor MHC antigens during development and later as mature cytotoxic lymphocytes. Further study is needed to understand how the cis-recognition of transferred donor MHC ligand influences the selection and maintenance of tolerant NK cells in prenatal chimeras.
    Chimerism. 10/2013; 4(4).
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    ABSTRACT: Postnatal vasculogenesis mediated via endothelial progenitor cells (EPCs) contributes to re-endothelialization and augments neovascularization after ischemia and tissue injury, providing a novel therapeutic application. However, controversy exists with respect to the origin, identification, and contributions of the EPCs to neovascularization, necessitating further study. Bone marrow (BM) or circulating cells expressing cd133/vascular endothelial growth factor receptor 2 include those with endothelial progenitor capacity. Increasing evidence suggests that there are additional BM-derived (myeloid; mesenchymal cells) and non-BM-derived (peripheral and cord-blood; tissue-resident) cell populations which also give rise to endothelial cells (ECs) and contribute to re-endothelialization and growth factor release after ischemia and tissue injury. Currently, EPCs are being used as diagnostic markers for the assessment of cardiovascular and tumor risk/progression. Techniques aimed at enhancing ex vivo expansion and the therapeutic potential of these cells are being optimized. Mobilization and EPC-mediated neovascularization are critically regulated. Stimulatory (growth factors, statins, and exercise) or inhibitory factors (obesity, diabetes, and other cardiovascular diseases) modulate EPC numbers and function. Recruitment and incorporation of EPCs require a coordinated sequence of signaling events, including adhesion, migration (by integrins), and chemoattraction. Finally, EPCs differentiate into ECs and/or secrete angiogenic growth factors. These cells are highly plastic, and depending on the microenvironment and presence of other cells, EPCs transdifferentiate and/or undergo cell fusion and become cells of a different lineage. Therefore, in vitro culture conditions should be optimized to mimic the in vivo milieu to fully characterize the biological function and contribution of EPCs to postnatal vasculogenesis. Advances in characterization of the EPC biology and enhancement of EPC functions are required. In addition, innovative tissue-engineered carrier matrices that permit embedding of EPCs and provide optimal conditions for EPC survival and endothelial outgrowth will further contribute to EPC-mediated therapeutic applications in wound healing and ischemia repair.
    Advances in wound care. 07/2013; 2(6):283-295.
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    ABSTRACT: BACKGROUND: Sacrococcygeal teratoma (SCT) is one of the most common neonatal and fetal tumors. SCT pelvic mass effect and the need for aggressive surgical resection, create potential for urologic co-morbidity. We reviewed our experience with SCTs and propose a rational plan for urologic surveillance. METHODS: We retrospectively reviewed all patients with SCT evaluated at our institution from 2004 to 2011. We collected data on the need for reconstructive surgery related to the urologic co-morbidity, the time to detection of urologic co-morbidity, and length of follow-up. RESULTS: We identified 28 patients evaluated during the study period with a median follow-up of 3.1 year (range 0.14-13.4). The Altman classifications were-type I: 7 (25%), II: 15 (53.6%), and III: 6 (21.4%). Eighteen (64.3%) patients had an associated urologic co-morbidity: 12 (42.9%) patients had hydronephrosis, VUR-10 (35.7%), NGB-13 (46.4%), and 4 (14.3%) developed ≥CKD2. When comparing the patients according to Altman classification, there was a trend towards more urologic co-morbidity in patients with increasing pelvic involvement, P = 0.06. Eleven patients (39.3%) had delayed urologic evaluation and five (17.9%) required reconstructive urologic surgery. In comparing these groups, 4 of 11 (36.4%) undergoing delayed urologic evaluation progressed to reconstruction, as opposed to only one of 17 (5.7%) with urologic evaluation within first year of life (P-value = 0.06). CONCLUSION: Urologic co-morbidities are common in children with SCT and appear most common in patients with more pelvic tumor involvement (≥Altman II). A risk-adapted approach to urologic surveillance is proposed. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 06/2013; · 2.35 Impact Factor
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    ABSTRACT: The mucosa of alimentary tract heals more rapidly than cutaneous wounds. The underlying mechanisms of this enhanced healing have not been completely elucidated. Constant exposure to salivary growth factors has been shown to play a critical role in mucosal homeostasis and tissue repair. Angiogenesis also has an essential role in successful wound repair. One of the main angiogenic growth factors, vascular endothelial growth factor (VEGF), has a pleiotropic role in tissue repair via neovascularization, reepithelialization, and regulation of extracellular matrix. We have previously reported a critical role for salivary VEGF in bowel adaptation after small bowel resection. We hypothesize that salivary VEGF is an essential stimulus for oral mucosal tissue repair, and use the murine palatal wound model to test our hypothesis. In a loss-of-function experiment, we removed the primary source of VEGF production through selective submandibular gland (SMG) sialoadenectomy in a murine model and observed the effects on wound closure and neovascularization. We then performed a selective loss-of-function experiment using the protein VEGF-Trap to inhibit salivary VEGF. In a gain-of-function experiment, we supplemented oral VEGF following SMG sialoadenectomy. After SMG sialoadenectomy, there was significant reduction in salivary VEGF level, wound closure, and vessel density. Lower levels of salivary VEGF were correlated with impaired neovascularization and reepithelialization. The selective blockade of VEGF using VEGF-Trap resulted in a similar impairment in wound healing and neovascularization. The sole supplementation of oral VEGF after SMG sialoadenectomy rescued the impaired wound healing phenotype and restored neovascularization to normal levels. These data show a novel role for salivary-VEGF in mucosal wound healing, and provide a basis for the development of novel therapeutics aimed at augmenting wound repair of the oral mucosa, as well as wounds at other sites in the alimentary tract.
    Wound Repair and Regeneration 06/2013; · 2.76 Impact Factor
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    ABSTRACT: Mid-gestational (E14.5) fetal wounds heal regeneratively with attenuated inflammation and high levels of hyaluronan (HA) in their extracellular matrix (ECM), whereas late-gestational (E18.5) fetal wounds heal with scarring. IL-10 plays an essential role in the fetal regenerative phenotype and is shown to recapitulate scarless wound healing postnatally. We hypothesize a novel role of IL-10 as a regulator of HA in the ECM. Murine fetal fibroblasts (FFb) from C57Bl/6 and IL-10-/- mice were evaluated in vitro. Pericellular matrix (PCM) and HA synthesis were quantified using a particle exclusion assay and ELISA. The effects of hyaluronidase and hyaluronan synthase (HAS) inhibitor (4-methylumbelliferone[4-MU]) were evaluated. An ex vivo fetal forearm culture incisional wound model comparing mid-gestation and late-gestation fetuses was used to evaluate IL-10's effect on HA-rich ECM production with pentachrome and immunohistochemistry. FFb produce a robust HA-rich PCM which is IL-10 dependent and attenuated with hyaluronidase and HAS inhibition. Mid-gestation fetal wounds produce more ground substance and HA than late-gestation fetal wounds. IL-10 in late-gestation fetal wounds results in elevated ground substance levels and HA staining. Our data demonstrate that IL-10 regulates an HA-rich ECM deposition, suggesting a novel non-immunoregulatory mechanism of IL-10 in mediating regenerative wound healing.
    Journal of Pediatric Surgery 06/2013; 48(6):1211-1217. · 1.38 Impact Factor
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    ABSTRACT: BACKGROUND: Sacrococcygeal teratoma is the most common neonatal tumor. Fetuses with large tumors may develop hydrops from a high cardiac output state (HCOS) and progress rapidly to fetal demise. We postulate that the prenatal solid tumor volume index (STVI), or the ratio of solid tumor volume to the estimated fetal weight (EFW), has greater impact than the total tumor volume in outcome prediction. METHODS: A retrospective chart review of all sacrococcygeal teratoma patients (n = 38) between 2005 and 2012 was conducted. Total tumor volume and percent of solid component were calculated by magnetic resonance imaging and then normalized by dividing them by either head circumference or EFW. Outcomes measured were survival, hydrops or high cardiac output state, defined as a combined ventricular output of >625 mL/min/kg with abnormal Doppler or echocardiogram findings. RESULTS: Thirty-one patients were included in the study. All deaths (n = 7) had either high cardiac output state or hydrops. At a total tumor volume/EFW >0.16, the patient was 17 times more likely to develop HCOS/hydrops (P = 0.001) with 81.25% sensitivity and 86.67% specificity. At a STVI >0.09, the patient was 120 times more likely to develop HCOS/hydrops (P < 0.0001) with 81.25% sensitivity and 100% specificity. CONCLUSIONS: While total tumor volume aids in stratifying patients into high risk categories, STVI (solid tumor volume/EFW) is a better predictor of adverse outcomes. This data will allow us to identify patients who are high risk for cardiac compromise and guide appropriate therapy.
    Journal of Surgical Research 05/2013; · 2.02 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVE:Pediatric patients are at risk for developing pressure ulcers (PUs) and associated pain, infection risk, and prolonged hospitalization. Stage III and IV ulcers are serious, reportable events. The objective of this study was to develop and implement a quality-improvement (QI) intervention to reduce PUs by 50% in our ICUs.METHODS:We established a QI collaborative leadership team, measured PU rates during an initial period of rapid-cycle tests of change, developed a QI bundle, and evaluated the PU rates after the QI implementation. The prospective study encompassed 1425 patients over 54 351 patient-days in the PICU and NICU.RESULTS:The PU rate in the PICU was 14.3/1000 patient-days during the QI development and 3.7/1000 patient-days after QI implementation (P < .05), achieving the aim of 50% reduction. The PICU rates of stages I, II, and III conventional and device-related PUs decreased after the QI intervention. The PU rate in the NICU did not change significantly over time but remained at a mean of 0.9/1000 patient-days. In the postimplementation period, 3 points were outside the control limits, primarily due to an increase in PUs associated with pulse oximeters and cannulas.CONCLUSIONS:The collaborative QI model was effective at reducing PUs in the PICU. Pediatric patients, particularly neonates, are at risk for device-related ulcers. Heightened awareness, early detection, and identification of strategies to mitigate device-related injury are necessary to further reduce PU rates.
    PEDIATRICS 05/2013; · 4.47 Impact Factor
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    ABSTRACT: BACKGROUND: The midgestational fetus is capable of regenerative healing. We have recently demonstrated a novel role for the anti-inflammatory cytokine interleukin 10 (IL-10) as a regulator of hyaluronan (HA) in the extracellular matrix. The signaling pathway of IL-10 has been studied in monocytes but is unknown in dermal fibroblasts. We hypothesized IL-10 signals through its primary receptor, IL-10R1, to activate STAT3, resulting in HA synthesis. METHODS: Murine midgestational (E14.5) fetal fibroblasts were evaluated in vitro. Pericellular matrix was quantified using a particle exclusion assay. STAT3 levels and cellular localization were evaluated by Western blot/band densitometry and immunocytochemistry/confocal microscopy. HA levels were quantified by enzyme-linked immunosorbent assay. The effects of IL-10R1 signal blockade by a neutralizing antibody and STAT3 inhibition were evaluated. An ex vivo midgestation fetal forearm culture incisional wound model in control and transgenic IL-10-/- mice was used to evaluate the role of STAT3 on the extracellular matrix. RESULTS: Fetal fibroblasts produce a robust hyaluronan-rich pericellular matrix that is IL-10R1 and STAT3 dependent. Inhibition of IL-10R1 signaling results in decreased phosphorylated STAT3 levels and inhibition of nuclear localization. Inhibition of STAT3 results in decreased HA production. At day 3, midgestation fetal wounds have efficient re-epithelialization, which is significantly slowed in IL-10-/- wounds at the same gestation and with inhibition of STAT3. CONCLUSIONS: Our data demonstrate that IL-10 regulates HA synthesis through its primary receptor IL-10R1 and STAT3 activation. This supports a novel nonimmunoregulatory mechanism of IL-10 in its role in fetal regenerative wound healing.
    Journal of Surgical Research 04/2013; · 2.02 Impact Factor
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    ABSTRACT: Background/Purpose Ovarian torsion (OT) is a clinical diagnosis with a variable presentation. The aim of this study was to develop a practical scoring system to predict patients with OT in the pediatric population to facilitate more accurate diagnosis.Methods A retrospective study evaluating menarchal pediatric patients (1998 to 2005) with surgically confirmed OT (n = 28) compared with patients with abdominal pain and surgically confirmed non-OT (n = 26). Histogram analysis was performed to determine threshold values and used to generate the OT composite index (OT-CI).Results Four factors were independently associated with OT: ovarian ratio, ovarian volume, nausea, and duration of pain. Arterial and venous Doppler flows were not associated with OT. The OT-CI was more accurate than any individual factor. There were no cases of OT in patients with OT-CI scores < 3. Patients with score ≥ 3 had 100% sensitivity and 65.3% specificity. A score ≥ 5 has 100% specificity.Conclusions The OT-CI is a practical scoring system combining clinical and radiologic findings to more accurately predict OT. An OT-CI score < 3 is strong evidence against OT in pediatric menarchal patients, which may minimize unnecessary surgical intervention. In contrast, scores ≥ 3 should be considered for surgical intervention to maximize ovarian salvage.
    European Journal of Pediatric Surgery 04/2013; · 0.84 Impact Factor
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    ABSTRACT: BACKGROUND: The current research environment for academic surgeons demands that extramural funding be obtained. Financial support from the National Institutes of Health (NIH) is historically the gold standard for funding in the biomedical research community, with the R01 funding mechanism viewed as indicator of research independence. The NIH also supports a mentor-based career development mechanism (K-series awards) in order to support early-stage investigators. The goal of this study was to investigate the grants successfully awarded to pediatric surgeon-scientists and then determine the success of the K-series award recipients at achieving research independence. METHODS: In July 2012, all current members of the American Pediatric Surgery Association (APSA) were queried in the NIH database from 1988-2012 through the NIH Research Portfolio Online Reporting Tools. The following factors were analyzed: type of grant, institution, amount of funding, and funding institute or center. RESULTS: Among current APSA members, there have been 83 independent investigators receiving grants, representing 13% of the current APSA membership, with 171 independent grants funded through various mechanisms. Six percent currently have active NIH funding, with $7.2 million distributed in 2012. There have been 28 K-series grants awarded. Of the recipients of expired K08 awards, 39% recipients were subsequently awarded an R01 grant. A total of 63% of these K-awarded investigators transitioned to an independent NIH award mechanism. CONCLUSIONS: Pediatric surgeon-scientists successfully compete for NIH funding. Our data suggest that although the K-series funding mechanism is not the only path to research independence, over half of the pediatric surgeons who receive a K-award are successful in the transition to independent investigator.
    Journal of Surgical Research 04/2013; · 2.02 Impact Factor
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    ABSTRACT: BACKGROUND: Cell-specific gene transfer and sustained transgene expression are goals of cutaneous gene therapy. Pseudotyping strategy with adeno-associated viral (AAV) vectors has the potential to confer unique cellular tropism and transduction efficiency. We hypothesize that pseudotyped AAV vectors have differential tropism and transduction efficiency under normal and wound conditions in dermal fibroblasts. MATERIALS AND METHODS: We packaged AAV2 genome with green fluorescent protein reporter in capsids of other serotypes, AAV5, AAV7, and AAV8, producing pseudotyped vectors AAV2/5, AAV2/7, and AAV2/8, respectively. Murine and human dermal fibroblasts were transduced by the different pseudotypes for 24 h at multiplicities of infection 10(2), 10(3), 10(4), and 10(5). We assessed transduction efficiency at days 3 and 7. Experiments were repeated in a simulated wound environment by adding 10 ng/mL platelet-derived growth factor-B to culture media. RESULTS: Transduction efficiency of the pseudotyped AAV vectors was dose dependent. Multiplicity of infection 10(5) resulted in significantly higher gene transfer. Under normal culture conditions, the pseudotyping strategy conferred differential transduction of dermal fibroblasts, with significantly enhanced transduction of murine cells by AAV2/5 and AAV2/8 compared with AAV2/2. Adeno-associated virus 2/8 was more efficacious in transducing human cells. Under wound conditions, transduction efficiency of AAV2/2, 2/5, and 2/8 was significantly lower in murine fibroblasts. At day 3 under wound conditions, all vectors demonstrated similar transduction efficiency, but by day 7, the three pseudotyped vectors transduced significantly more murine cells compared with AAV2/2. However, in human cells, there was no significant difference in the transduction efficiency of each pseudotype between normal and wound conditions at both 3 and 7 d. CONCLUSIONS: The AAV pseudotyping strategy represents a gene transfer technology that can result in differential transduction of dermal fibroblasts. The differences in transduction efficiency in murine and human dermal fibroblasts in both the normal and wound environment highlight issues with translatability of gene transfer techniques. These data provide a template for using pseudotyped AAV vectors in cutaneous applications.
    Journal of Surgical Research 04/2013; · 2.02 Impact Factor
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    ABSTRACT: Objective: To determine whether total fetal lung volumes estimated by MRI could predict lethal pulmonary hypoplasia in a cohort of fetuses with cervical teratomas. Methods: We performed a retrospective cohort study of fetal cervical teratomas from January 1, 2005, through April 1, 2012. The primary outcome was the ability of total lung volumes measured by MRI to predict neonatal mortality specifically due to pulmonary hypoplasia. Measured lung volumes were compared to previously reported normal values. The percent of observed-to-expected lung volume and the percent predicted lung volume were calculated. The positive and negative predictive values were calculated for each variable. Results: Fetal MRI-derived total lung volumes 1 standard deviation below the median for gestational age had a positive predictive value of 100% in predicting lethal pulmonary hypoplasia. Conversely, total lung volumes above this level were uniformly associated with pulmonary survival (100% negative predictive value). Additionally, percent predicted lung volume ≤75.7 and observed-to-expected lung volume ≤68.3 were associated with lethal pulmonary hypoplasia. Conclusion: In this small cohort, MRI-estimated lung volumes were helpful in predicting the presence of pulmonary hypoplasia complicating fetal cervical teratoma.
    Fetal Diagnosis and Therapy 02/2013; · 1.90 Impact Factor
  • Sundeep G Keswani, Alice King
    Journal of Surgical Research 02/2013; · 2.02 Impact Factor
  • Alice King, Swathi Balaji, Sundeep G Keswani
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    ABSTRACT: The development of the integumentary system is a series of events that starts in utero and continues throughout life. Although at birth, skin in full-term infants is anatomically mature, functional maturity develops during the first year of life. Pediatric skin transitions again with the onset of puberty. At each stage, there are changes in transepidermal water loss, skin hydration, and skin acidity that define the specific period of development.
    Facial plastic surgery clinics of North America 02/2013; 21(1):1-6.

Publication Stats

291 Citations
89.58 Total Impact Points

Institutions

  • 2007–2014
    • Cincinnati Children's Hospital Medical Center
      • Division of Pediatric General and Thoracic Surgery
      Cincinnati, Ohio, United States
  • 2003–2013
    • The Children's Hospital of Philadelphia
      • Children's Institute for Surgical Science
      Philadelphia, Pennsylvania, United States
    • Hospital of the University of Pennsylvania
      Philadelphia, Pennsylvania, United States
  • 2004–2012
    • University of Cincinnati
      • College of Medicine
      Cincinnati, Ohio, United States
  • 2002
    • Louisiana State University Health Sciences Center New Orleans
      • Department of Surgery
      Baton Rouge, LA, United States