Childrens Memorial Hospital of Chicago

Chicago, IL, United States

Childrens Memorial Hospital of Chicago

Chicago, IL, United States
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Kollhoff D.M.,Loyola University | Cheng E.Y.,Northwestern University | Cheng E.Y.,Childrens Memorial Hospital of Chicago | Sharma A.K.,Northwestern University | Sharma A.K.,Childrens Memorial Hospital of Chicago
Regenerative Medicine | Year: 2011

Many congenital and acquired anomalies affect the genitourinary tract, necessitating surgical intervention. Among these are bladder exstrophy, hypospadias, epispadias, posterior urethral valves, myelomeningocele, bladder carcinoma, urethral stricture disease, stress urinary incontinence, pelvic organ prolapse, vesicoureteral reflux and traumatic injuries of the urinary tract. Surgical repair of these conditions often utilizes skin, oral mucosa or bowel autograft or xenograft material to replace missing tissue or to augment inadequate tissues. These materials are often sufficient to restore the basic anatomy of the organ to which they are being grafted, but they usually do not completely restore normal function. In addition, postoperative complications are common, especially in the case of bladder augmentation or neobladder creation with autologous bowel. The complications and inherent limitations of these procedures may be mitigated by the availability of alternative tissue sources. Therefore, there has been a great deal of interest in developing tissues engineered from autologous materials, such as mature bladder cells, bone marrow-derived stem cells and adipose tissue. Ideally, an engineered tissue would restore or preserve the normal function of the organ it is augmenting or replacing. In addition, the engineered tissue should be nonimmunogenic to minimize rejection or foreign-body reactions. For the purposes of this article, we will focus on selection of scaffolding materials, selection of cell sources, and the current applications and potential future roles of tissue engineering in urology. © 2011 Future Medicine Ltd.


Sharma A.K.,Childrens Memorial Hospital of Chicago | Sharma A.K.,Northwestern University
Regenerative Medicine | Year: 2011

Patients that are afflicted with dysfunctional urinary bladders due to developmental defect, trauma or malignant transformation have limited treatment options that would allow for complete recapitulation of the urinary bladder. Hence, novel tissue engineering techniques that are successful in regenerating functional urinary bladder tissue for replacement therapy would be invaluable. Current tissue engineering techniques are hampered by several problems including choice of appropriate cell type, inadequate development of new blood vessels to the regenerated tissue, tissue innervation and primitive bioscaffold design. This article describes the recent advances in stem cell biology and the material sciences to address these problems, and attempts to improve upon current tissue engineering techniques to make successful regeneration of urinary bladder tissue a reality. © 2011 Future Medicine Ltd.


Thaker H.,Childrens Memorial Hospital of Chicago | Sharma A.K.,Childrens Memorial Hospital of Chicago | Sharma A.K.,Northwestern University
Stem Cells International | Year: 2012

The need for a consistent therapeutic approach to tendon injury repair is long overdue. Patients with tendon microtears or full ruptures are eligible for a wide range of invasive and non invasive interventions, often subjectively decided by the physician. Surgery produces the best outcomes, and while studies have been conducted to optimize graft constructs and to track outcomes, the data from these studies have been inconclusive on the whole. What has been established is a clear understanding of healthy tendon architecture and the inherent process of healing. With this knowledge, tissue regeneration efforts have achieved immense progress in scaffold design, cell line selection, and, more recently, the appropriate use of cytokines and growth factors. This paper evaluates the plasticity of bone-marrow-derived stem cells and the elasticity of recently developed biomaterials towards tendon regeneration efforts. Mesenchymal stem cells (MSCs), hematopoietic progenitor cells, and poly(1,8-octanediol co-citrate) scaffolds (POC) are discussed in the context of established grafting strategies. With POC scaffolds to cradle the growth of MSCs and hematopoietic progenitor cells, developing a fibroelastic network guided by cytokines and growth factors may contribute towards consistent graft constructs, enhanced functionality, and better patient outcomes. © Copyright 2012 Hatim Thaker and Arun K. Sharma.


Sharma A.K.,Childrens Memorial Hospital of Chicago | Sharma A.K.,Northwestern University | Bury M.I.,Childrens Memorial Hospital of Chicago | Marks A.J.,Childrens Memorial Hospital of Chicago | And 7 more authors.
Stem Cells | Year: 2011

Animal models that have been used to examine the regenerative capacity of cell-seeded scaffolds in a urinary bladder augmentation model have ultimately translated poorly in the clinical setting. This may be due to a number of factors including cell types used for regeneration and anatomical/physiological differences between lower primate species and their human counterparts. We postulated that mesenchymal stem cells (MSCs) could provide a cell source for partial bladder regeneration in a newly described nonhuman primate bladder (baboon) augmentation model. Cell-sorted CD105+/CD73+/CD34-/CD45- baboon MSCs transduced with green fluorescent protein (GFP) were seeded onto small intestinal submucosa (SIS) scaffolds. Baboons underwent an approximate 40%-50% cystectomy followed by augmentation cystoplasty with the aforementioned scaffolds or controls and finally enveloped with omentum. Bladders from sham, unseeded SIS, and MSC/SIS scaffolds were subjected to trichrome, H&E, and immunofluorescent staining 10 weeks postaugmentation. Immunofluorescence staining for muscle markers combined with an anti-GFP antibody revealed that >90% of the cells were GFP+/muscle marker+ and >70% were GFP+/Ki-67+ demonstrating grafted cells were present and actively proliferating within the grafted region. Trichrome staining of MSC/SIS-augmented bladders exhibited typical bladder architecture and quantitative morphometry analyses revealed an approximate 32% and 52% muscle to collagen ratio in unseeded versus seeded animals, respectively. H&E staining revealed a lack of infiltration of inflammatory cells in grafted animals and in corresponding kidneys and ureters. Simple cystometry indicated recovery between 28% and 40% of native bladder capacity. Data demonstrate MSC/SIS composites support regeneration of bladder tissue and validate this new bladder augmentation model. © AlphaMed Press.


Sharma A.K.,Childrens Memorial Hospital of Chicago | Sharma A.K.,Northwestern University | Bury M.I.,Childrens Memorial Hospital of Chicago | Fuller N.J.,Childrens Memorial Hospital of Chicago | And 12 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2012

The ultimate success of in vivo organ formation utilizing ex vivo expanded "starter" tissues relies heavily upon the level of vascularization provided by either endogenous or artificial induction of angiogenic or vasculogenic events. To facilitate proangiogenic outcomes and promote tissue growth, an elastomeric scaffold previously shown to be instrumental in the urinary bladder regenerative process was modified to release proangiogenic growth factors. Carboxylic acid groups on poly(1,8-octanediol-co-citrate) films (POCfs) were modified with heparan sulfate creating a heparan binding POCf (HBPOCf). Release of proangiogenic growth factors vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and insulin-like growth factor 1 (IGF-1) from HBPOCfs demonstrated an approximate threefold increase over controls during a 30-day time course in vitro. Atomic force microscopy demonstrated significant topological differences between films. Subcutaneous implantation of POCf alone, HBPOCf, POCf-VEGF, and HBPOCf-VEGF within the dorsa of nude rats yielded increased vascular growth in HBPOCf-VEGF constructs. Vessel quantification studies revealed that POCfs alone contained 41.1 ± 4.1 vessels/mm 2, while HBPOCf, POCf-VEGF, and HBPOCF-VEGF contained 41.7 ± 2.6, 76.3 ± 9.4, and 167.72 ± 15.3 vessels/mm 2, respectively. Presence of increased vessel growth was demonstrated by CD31 and vWF immunostaining in HBPOCf-VEGF implanted areas. Data demonstrate that elastomeric POCfs can be chemically modified and possess the ability to promote angiogenesis in vivo. Copyright © 2011 Wiley Periodicals, Inc.


Le B.,Northwestern University | Sharma V.,Northwestern University | Kim D.,Northwestern University | Dupree J.,Northwestern University | Maizels M.,Childrens Memorial Hospital of Chicago
Journal of Pediatric Urology | Year: 2013

Objectives: Primary care physicians are the routine providers of neonatal circumcision, yet urologists commonly manage the complications. We previously identified a need for improved formalized training in neonatal circumcisions among ob-gyn residents. Here we extend the needs assessment to urology residents. Methods: From Nov 2008 to Nov 2009, ob-gyn and urology residents at our institution were given an online survey to assess comfort, education, and proficiency in pre-operative evaluation and performance of circumcisions. Results: 26/35 (74%) ob-gyn and 12/17 (65%) urology residents responded to the survey. 62% of ob-gyn and 33% of urology residents intended to perform neonatal circumcisions in practice. Both groups described having little formal training in neonatal circumcision. Ob-gyn residents felt more comfortable than urology residents in performing neonatal circumcisions [mean 5.9 vs. 4.3, p = 0.001; 1 (very uncomfortable) - 7 (very comfortable)], though urology residents' comfort level increased with resident year. Ob-gyn residents felt less comfortable than urology residents (mean 3.9 vs. 5.1, p = 0.031) evaluating if a newborn penis may undergo circumcision safely. Urology residents performed better than ob-gyn residents at identifying contraindications to routine circumcision from 10 scenarios (mean 63% vs. 42% p < 0.001). Both felt that an online module was a good alternative to practical experience. Conclusions: At our institution, ob-gyn and urology residents have little formalized training in neonatal circumcision. While ob-gyn residents are comfortable performing circumcisions, they feel less comfortable evaluating the newborn penis and correctly managed fewer scenarios than did urology residents. This highlights the need for further curriculum development and formalized training. © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.


Davis B.H.,University of North Carolina at Charlotte | MacLagan M.,University of Canterbury | Karakostas T.,Childrens Memorial Hospital of Chicago | Hsiang S.,North Carolina State University | Shenk D.,University of North Carolina at Charlotte
Topics in Geriatric Rehabilitation | Year: 2011

This article reports 3 pilot studies of cognitively impaired (CI) persons responding to different types of questions. Pilot 1 analyzed responses of 7 people at high CI risk and 7 people at low CI risk to questions asked during seated conversation. High-risk participants paused longer before responding. Pilot 2 identified types of questions asked from 1 participant in seated conversations with 2 interviewers and analyzed her responses. Pilot 3 introduced a dual task, walking while answering an unexpected question. The CI participants paused longer before responding than controls. A subset of 6 timedistance parameters distinguished gait of the 2 participant groups. Copyright © 2011 Lippincott Williams & Wilkins.


Soltanolkotabi M.,Northwestern University | Schoeneman S.E.,Childrens Memorial Hospital of Chicago | Dipatri A.J.,Childrens Memorial Hospital of Chicago | Hurley M.C.,Northwestern University | And 5 more authors.
Interventional Neuroradiology | Year: 2012

Pilocytic astrocytomas are highly vascular, relatively common primary brain tumors in the pediatric population, but their association with a true arteriovenous malformation (AVM) is extremely rare. We describe an eight-year-old girl with a right supratentorial juvenile pilocytic astrocytoma (WHO grade I) with an angiographically documented AVM entangled in the tumor mass who presented with intracranial hemorrhage due to a ruptured anterior choroidal artery pseudoaneurysm encased in the lesion. The AVM nidus as well as the hemorrhage site was embolized with Onyx. A literature review revealed only one previous report of a true intermixture of these two lesions. We hypothesize whether the association of vascular malformations and primary brain tumors are merely coincidental or if they point to the existence of a distinct entity and/or a common etiologic factor.


PubMed | Childrens Memorial Hospital of Chicago
Type: Journal Article | Journal: Regenerative medicine | Year: 2011

Patients that are afflicted with dysfunctional urinary bladders due to developmental defect, trauma or malignant transformation have limited treatment options that would allow for complete recapitulation of the urinary bladder. Hence, novel tissue engineering techniques that are successful in regenerating functional urinary bladder tissue for replacement therapy would be invaluable. Current tissue engineering techniques are hampered by several problems including choice of appropriate cell type, inadequate development of new blood vessels to the regenerated tissue, tissue innervation and primitive bioscaffold design. This article describes the recent advances in stem cell biology and the material sciences to address these problems, and attempts to improve upon current tissue engineering techniques to make successful regeneration of urinary bladder tissue a reality.


PubMed | Childrens Memorial Hospital of Chicago
Type: | Journal: Stem cells international | Year: 2012

The need for a consistent therapeutic approach to tendon injury repair is long overdue. Patients with tendon microtears or full ruptures are eligible for a wide range of invasive and non invasive interventions, often subjectively decided by the physician. Surgery produces the best outcomes, and while studies have been conducted to optimize graft constructs and to track outcomes, the data from these studies have been inconclusive on the whole. What has been established is a clear understanding of healthy tendon architecture and the inherent process of healing. With this knowledge, tissue regeneration efforts have achieved immense progress in scaffold design, cell line selection, and, more recently, the appropriate use of cytokines and growth factors. This paper evaluates the plasticity of bone-marrow-derived stem cells and the elasticity of recently developed biomaterials towards tendon regeneration efforts. Mesenchymal stem cells (MSCs), hematopoietic progenitor cells, and poly(1,8-octanediol co-citrate) scaffolds (POC) are discussed in the context of established grafting strategies. With POC scaffolds to cradle the growth of MSCs and hematopoietic progenitor cells, developing a fibroelastic network guided by cytokines and growth factors may contribute towards consistent graft constructs, enhanced functionality, and better patient outcomes.

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