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Biomedical subjects

Anthony Atala

Publications and source records attributed to Anthony Atala.

At least 37 records · Page 2Linked to original sources
PubMed2005

Antiangiogenic properties of gold nanoparticles.

Here, we report an intrinsic property of gold nanoparticles (nanogold): they can interact selectively with heparin-binding glycoproteins and inhibit their activity. Gold nanoparticles specifically bound vascular permeability factor/vascular endothelial growth factor (VPF/VEGF)-165 and basic fibroblast growth factor, two endothelial cell mitogens and mediators of angiogenesis resulting in inhibition of endothelial/fibroblast cell proliferation in vitro and VEGF-induced permeability as well as angiogenesis in vivo. In contrast, nanogold did not inhibit VEGF-121 or epidermal growth factor, two non-heparin-binding growth factors, mediated cell proliferation. Gold nanoparticles significantly inhibited VEGF receptor-2 phosphorylation, intracellular calcium release, and migration and RhoA activation in vitro. These results report for the first time a novel property of gold nanoparticles to bind heparin-binding proteins and thereby inhibit their subsequent signaling events.

Angiogenesis Inhibitors↗
PubMed2005

Regeneration of urologic tissues and organs.

Patients suffering from a variety of urologic diseases may be treated with transplanted tissues and organs. However, there is a shortage of donor tissues and organs, which is worsening yearly owing to the ageing population. Scientists in the field of regenerative medicine and tissue engineering are applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured urologic tissues. This chapter reviews recent advances that have occurred in the regeneration of urologic organs and describes how these applications may offer novel therapies for patients with urologic disease.

Cloning, Organism↗
PubMed2005

Technology insight: Applications of tissue engineering and biological substitutes in urology.

Patients suffering from diseased or injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs, which is worsening yearly owing to the ageing population. Scientists in the field of regenerative medicine and tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. This article reviews recent advances in regenerative medicine and describes applications of biological substitutes that may offer novel therapies for patients with end-stage organ failure.

Bioartificial Organs↗
PubMed2005

Propagation, expansion, and multilineage differentiation of human somatic stem cells from dermal progenitors.

We isolated multipotential mesenchymal stem cells (MSC) from human postnatal dermal tissues. The isolated cells were expanded and maintained for over 100 population doublings with retention of their chromosomal complement and potential for multilineage differentiation. Progeny of cell lines established from a single dermal MSC could be differentiated into adipogenic, osteogenic, and myogenic lineages, consistent with the conclusion that we established a clonal, multipotential, somatic MSC cell line. This study is the first to show potential growth of multipotential human MSC cell lines from a single cell that can be used for the engineering of tissues in vivo. Clonal growth of MSCs presents profound implications in our understanding of differentiation and development, and should provide a valuable resource for tissue repair.

Adipocytes↗
PubMed2005

Early outcome following complete primary repair of bladder exstrophy in the newborn.

PURPOSE: Complete primary repair of bladder exstrophy (CPRE) represents a paradigm shift from the staged approach for surgical management. We present early clinical outcomes in our patients following CPRE. MATERIALS AND METHODS: From 1996 to 2004 all newborns with bladder exstrophy were treated with CPRE within 48 hours of birth. We reviewed parameters including transfusions (packed red blood cells), urethral meatal position, complications, findings on renal ultrasound and renal scan, and post-CPRE procedures and infections. RESULTS: A total of 16 boys and 7 girls were treated with CPRE. Followup ranged from 8 to 96 months. Twelve boys (75%) and 2 girls (29%) received packed red blood cells at CPRE (p = 0.066). The tubularized urethral plate could not be brought to the penile tip, resulting in hypospadias in 9 of 11 boys (82%) with the running suture technique and only 1 of 5 boys (20%) with the interrupted technique (p = 0.036). Of the 23 patients 6 had a total of 8 complications after CPRE. Vesicoureteral reflux was present in 17 of 23 patients. After CPRE a total of 93 endoscopic/surgical procedures (median 4, range 0 to 16 per patient) were performed. Five patients had 1 to 4 episodes of pyelonephritis, 16 of 23 had 1 or more episodes of asymptomatic bacteriuria and 5 had cortical defects on renal scan. CONCLUSIONS: We recommend that urethral closure during CPRE be performed with interrupted suture technique to prevent hypospadias. An aggressive approach should be taken toward reflux in the setting of urinary infection. Consideration should be given for repair of all aspects of the defect during CPRE, including bilateral ureteral reimplantation.

Bladder Exstrophy↗
PubMed2005

Magnetic resonance imaging of pelvic musculoskeletal and genitourinary anatomy in patients before and after complete primary repair of bladder exstrophy.

PURPOSE: We characterize pelvic soft tissue and bony anatomy of patients before and after complete primary repair of exstrophy (CPRE). MATERIALS AND METHODS: We evaluated 15 measurements on pelvic magnetic resonance imaging (MRI) in patients who underwent CPRE without osteotomy at our institution from 1996 to 2004. MRI protocols included axial, sagittal and coronal fast spin echo proton density sequences. Measurements were compared before and after CPRE using a paired t test, and between patients after CPRE, and age and gender matched controls using linear regression adjusting for the matched case-control groups. Patients older than 3 years with continent intervals longer than 3 hours after CPRE were compared to age and gender matched controls using linear regression. RESULTS: A total of 29 MRIs in 18 patients with exstrophy were available for analysis. Median patient age at postoperative MRI was 25 months (range 4 to 36). The configuration of the post-CPRE pelvis was significantly different from that of controls in all parameters measured including wider symphyseal diastasis (34.5 mm vs less than 1 mm) and more obtuse iliac wing (121 degrees vs 98 degrees), puborectalis (94 degrees vs 49 degrees) and ileococcygeus angles (111 degrees vs 98 degrees ). The anatomy of continent patients after CPRE was not significantly different from that of controls in most parameters measured. CONCLUSIONS: Comparison of the pelvic anatomy in patients before and after CPRE suggests that after CPRE patients have parameters that more closely approximate, but are still significantly different, from those of control patients. Patients with greater than 3-hour continent intervals after CPRE have anatomic parameters most similar to those of age matched controls.

Bladder Exstrophy↗
PubMed2005

Bladder growth and development after complete primary repair of bladder exstrophy in the newborn with comparison to staged approach.

PURPOSE: We assessed bladder growth and dynamics following complete primary repair of bladder exstrophy (CPRE) compared to the staged approach. MATERIALS AND METHODS: We reviewed the records of 16 boys and 7 girls who underwent CPRE within 3 days of life from 1996 to 2004 and compared them to the records of 8 boys and 6 girls treated with a staged repair from 1979 to 1996. Screening methods included voiding cystourethrogram, radionuclide cystogram and urodynamic study. We estimated growth curves for bladder capacity following repair in each group, and compared percent predicted bladder capacity (PPBC), compliance and detrusor overactivity between the CPRE and staged repair groups following bladder neck reconstruction. RESULTS: Bladder capacity in the staged repair group was 69.8 ml (95% CI 46.7-104.4) immediately after bladder neck reconstruction and increased by 15.0% per year thereafter (95% CI 6.2-24.5, p = 0.002). In the CPRE group bladder capacity was 29.0 ml (95% CI 21.3-39.5) initially and increased by 28.9% per year thereafter (95% CI 17.4-41.5, p <0.001). PPBC started at 45.6% (95% CI 35.7-55.5) and increased 1.2% per year (95% CI -1.1-3.5, p = 0.29) following repair for all genders and surgery groups. Compliance was 124.4% (95% CI 22.6-310.7, p = 0.01) greater in the CPRE group at all times following repair. Detrusor overactivity was present in 0 of 19 patients in the CPRE group and 6 of 13 (46%) in the staged group (exact p = 0.002). CONCLUSIONS: Within the CPRE group bladder stability was universal, and sphincter electromyography was normal suggesting no neuromuscular compromise of the pelvic floor. At early followup, our results suggest that PPBC is equivalent irrespective of gender or management. Further objective evaluation is needed in both groups.

Bladder Exstrophy↗
PubMed2005

Testicular hypotrophy does not correlate with grade of adolescent varicocele.

PURPOSE: Testicular hypotrophy is the most widely accepted indication for correcting adolescent varicocele. Previous studies in adolescents have shown a relationship between increasing grade of varicocele and the likelihood of testicular hypotrophy. As this relationship has significant clinical implications, we studied the correlation between grade and testicular volume disproportion in our adolescent varicocele population. MATERIALS AND METHODS: We reviewed the adolescent varicocele database at our institution. A total of 168 patients 8 to 21 years old were studied. We routinely calculated testis volumes using scrotal ultrasound. Testicular disproportion was calculated using the equation [(size of unaffected testis) - (size of affected testis)]/(size of unaffected testis) x 100%. Disproportion was categorized as less than 10%, 10% to 20% and more than 20%. Varicoceles were graded by an attending urologist with the patient standing, using the system of Dubin and Amelar. Analysis of variance and Pearson chi-square indicated no significant differences in volume differential between varicocele grades. RESULTS: Mean +/- SD volume differential was 18% +/- 15% for grade I, 25% +/- 20% for grade II and 19% +/- 14% for grade III. ANOVA revealed no significant difference in mean volume differential between the 3 varicocele grades (p = 0.10). When categorizing patients into 3 levels of volume differential (less than 10%, 10% to 20%, more than 20%) no significant correlation was observed between varicocele and volume differential (p = 0.48, chi-square test). CONCLUSIONS: Grade of varicocele does not correlate with presence or severity of testicular disproportion in adolescent boys with varicocele as measured by scrotal ultrasound.

Adolescent↗
PubMed2005

Tissue engineering of functional salivary gland tissue.

OBJECTIVES: Treatment of conditions that lead to salivary hypofunction, such as radiation induced xerostomia, is currently limited to the administration of saliva substitutes and sialogogues. The transient effect of these medications necessitates frequent administration, and systemic side effects may be intolerable. The creation of implantable, functional salivary gland tissue from autologous glandular cells would provide a physiologic solution to this problem. We investigated the feasibility of engineering such tissue in vivo. METHODS: Primary human salivary gland cells were grown, expanded, and seeded on biodegradable polymer scaffolds. A total of 48 scaffolds with cells and 16 control polymers without cells were implanted subcutaneously in athymic mice. The implants were retrieved 2, 4, and 8 weeks after the implantation for phenotypic and functional analyses. RESULTS: Human salivary gland epithelial cells retained their phenotypic and functional characteristics at all culture stages. Histologically, formation of acinar gland-like structures was observed within the engineered tissue by 4 weeks after implantation. Immunocytochemical and Western blot analyses of the implanted tissues demonstrated the expression of human a-amylase, cytokeratins AE1/AE3, and aquaporin-5 using cell-specific antibodies. Reverse-transcription polymerase chain reaction analyses confirmed the expression of human salivary type of alpha-amylase (sigma-amylase) mRNA. The retrieved tissues demonstrated the production of human alpha-amylase over time using a biochemical amylase detection system.

Animals↗
PubMed2005

Tumor cell-associated neuropilin-1 and vascular endothelial growth factor expression as determinants of tumor growth in neuroblastoma.

We sought to characterize the expression of vascular endothelial growth factor (VEGF) and its receptors in neuroblastoma (NBL) and to correlate the results with N-myc (MYCN) expression and in vivo growth of these tumors. Two representative human-derived NBL cell lines, SK-N-AS (AS) with low and SK-N-DZ (DZ) with a high MYCN copy number, were used for the study. We examined their proliferation, VEGF and VEGF receptor expression in vitro and xenograft tumor growth in vivo. In parallel, human NBL specimens were analyzed for expression of VEGF and neuropilin-1 (NRP-1). DZ cells exhibited a 4-fold higher proliferation rate than AS. In contrast, VEGF protein expression was significantly higher in AS cells. NRP-1 was the only VEGF receptor produced in AS and DZ cells in vitro and in vivo. Both AS and DZ cells formed tumors in athymic mice but AS tumors grew 3.5 times larger than DZ tumors and had larger diameter tumor vessels. VEGF and NRP-1 expression was also demonstrated in human NBL specimens. Our studies indicate that VEGF and VEGF receptor expression in NBL tumor cells are associated with tumor growth and that angiogenic factors may serve as a biological marker together with already established MYCN amplification.

Animals↗
PubMed2005

Tissue engineering, stem cells and cloning: current concepts and changing trends.

Organ damage or loss can occur from congenital disorders, cancer, trauma, infection, inflammation, iatrogenic injuries or other conditions and often necessitates reconstruction or replacement. Replacement may take the form of organ transplant. At present, there is a severe shortage of donor organs that is worsening with the aging of the population. Tissue engineering follows the principles of cell transplantation, materials science and engineering towards the development of biological substitutes that can restore and maintain normal tissue function. Therapeutic cloning involves the introduction of a nucleus from a donor cell into an enucleated oocyte to generate embryonic stem cell lines whose genetic material is identical to that of its source. These autologous stem cells have the potential to become almost any type of cell in the adult body, and thus would be useful in tissue and organ replacement applications. This paper reviews recent advances in stem cell research and regenerative medicine, and describes the clinical applications of these technologies as novel therapies for tissue or organ loss.

Animals↗
PubMed2005

Applications of tissue engineering in the genitourinary tract.

Congenital abnormalities and acquired disorders can lead to organ damage or loss of tissue within the genitourinary tract. For reconstructive purposes, tissue-engineering efforts are currently underway for virtually every type of tissue and organ within the urinary tract. Tissue engineering incorporates the fields of cell transplantation, materials science and engineering for the purpose of creating functional replacement tissue. This article reviews some of the principles of tissue engineering and some of the applications of these principles to the genitourinary tract.

Biocompatible Materials↗
PubMed2004

Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy.

: BACKGROUND: Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs which is worsening yearly due to the aging population. Scientists in the field of tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Both therapeutic cloning (nucleus from a donor cell is transferred into an enucleated oocyte), and parthenogenesis (oocyte is activated and stimulated to divide), permit extraction of pluripotent embryonic stem cells, and offer a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. The present article reviews recent progress in tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.

Journal Article↗
PubMed2004

Endoscopic treatment of vesicoureteral reflux with autologous chondrocytes: postoperative sonographic features.

PURPOSE: To analyze sonographic imaging features of renal collecting systems, ureters, and bladder in 32 children after endoscopic treatment of vesicoureteral reflux with autologous chondrocytes and to determine whether any features are associated with persistent reflux. MATERIALS AND METHODS: Sonograms obtained at mean intervals of 1.4 and 12 months after treatment were compared with cystograms obtained at mean intervals of 2.7 and 12 months. Sonograms were analyzed for chondrocyte mound contour and volume, changes in mound volume over time, and presence of hydroureteronephrosis. Mean differences in mound volume were detected with paired t tests in 14 patients with early and late sonograms available for review. RESULTS: Early cystograms and sonograms were available for 25 of 32 patients (45 of 56 treated ureters). Reflux occurred in 16 of 45 ureters. In 16 ureters, chondrocyte mounds were absent in six, unilobed in seven, and multilobed in three. In 29 treated ureters without reflux, mounds were unilobed in 28 and multilobed in one. Three patients had mild hydronephrosis and one had distal hydroureter; these conditions resolved. Late cystograms and sonograms were available in 18 of 22 patients (30 of 38 treated ureters). Reflux occurred in seven of 30 ureters. In seven ureters, mounds were unilobed in five and multilobed in two. In 23 treated ureters without reflux, mounds were unilobed in 21 and multilobed in two. One patient had mild hydronephrosis that resolved. In 14 patients with early and late sonograms available for review, mean mound volume in late group (0.37 cm3 +/- 0.25 [standard deviation]) was significantly smaller than that in early group (0.56 cm3 +/- 0.39; P =.004, paired t test). CONCLUSION: Absence of chondrocyte mound or presence of multilobed mound contour was associated with persistent reflux. Mean mound volume decreased over time. Treatment-induced hydroureteronephrosis was uncommon and self-limited.

Adolescent↗
PubMed2004

Stem cells: cross-talk and developmental programs.

The thesis advanced in this essay is that stem cells-particularly those in the nervous system-are components in a series of inborn 'programs' that not only ensure normal development, but persist throughout life so as to maintain homeostasis in the face of perturbations-both small and great. These programs encode what has come to be called 'plasticity'. The stem cell is one of the repositories of this plasticity. This review examines the evidence that interaction between the neural stem cell (as a prototypical somatic stem cell) and the developing or injured brain is a dynamic, complex, ongoing reciprocal set of interactions where both entities are constantly in flux. We suggest that this interaction can be viewed almost from a 'systems biology' vantage point. We further advance the notion that clones of exogenous stem cells in transplantation paradigms may not only be viewed for their therapeutic potential, but also as biological tools for 'interrogating' the normal or abnormal central nervous system environment, indicating what salient cues (among the many present) are actually guiding the expression of these 'programs'; in other words, using the stem cell as a 'reporter cell'. Based on this type of analysis, we suggest some of the relevant molecular pathways responsible for this 'cross-talk' which, in turn, lead to proliferation, migration, cell genesis, trophic support, protection, guidance, detoxification, rescue, etc. This type of developmental insight, we propose, is required for the development of therapeutic strategies for neurodegenerative disease and other nervous system afflictions in humans. Understanding the relevant molecular pathways of stem cell repair phenotype should be a priority, in our view, for the entire stem cell field.

Brain↗
PubMed2004

Peripheral nerve regeneration using acellular nerve grafts.

Long gap peripheral nerve injuries usually require a graft to facilitate axonal regeneration into the distal nerve stump. The use of autografts is often limited because of graft availability and donor-site morbidity. We investigated whether acellular nerve allografts would provide an appropriate channel for the promotion and induction of sciatic nerve regeneration in rats. Axons sprouted from the proximal portion and reached the distal portion in the 1 cm-long grafts by 1 month. The number of axons in the regenerated nerves was similar to that of normal nerves at 1 month. Loading the grafts with betaNGF and VEGF increased the number and mean diameter of axons and neovascularization in the regenerated nerves at 1 month. The motor conduction velocity increased over time and reached 63 +/- 10% of that of normal nerves at 6 months. The nerve injuries treated with the acellular grafts had a significant improvement in motor, nociception, and proprioception function compared to untreated nerves. The results from this study suggest that acellular nerve allografts may be a useful biomaterial for functional peripheral nerve regeneration.

Animals↗
PubMed2004

A novel use of centrifugal force for cell seeding into porous scaffolds.

A novel rotor was constructed to allow for the seeding of porous scaffolds via centrifugal force. Using cell seeding times of 10 min, this method placed significantly (roughly 3-fold) more cells into poly(glycolic acid) scaffolds than 24 h of spinner flask seeding or static seeding. There were no significant differences in the mitochondrial activity per cell between the 3 seeding methods. Cell distribution was noted to be homogeneous throughout the scaffold thickness for the centrifugation method, as opposed to surface seeding for the spinner flask method. Centrifugation was especially efficient at low cell concentrations (1.33 x 10(5) cells/ml). This system is useful for the seeding of biomaterials having cylindrical or planar geometries, and may be used under conditions that require low cell numbers and/or short seeding time periods.

Bioreactors↗