The Use of Regenerative Medicine in the Management of Invasive Bladder Cancer

Southern Alberta Institute of Urology, University of Calgary, Alberta, Canada T2V 1P9.
Advances in Urology 08/2012; 2012:653652. DOI: 10.1155/2012/653652
Source: PubMed


Muscle invasive and recurrent nonmuscle invasive bladder cancers have been traditionally treated with a radical cystectomy and urinary diversion. The urinary diversion is generally accomplished through the creation of an incontinent ileal conduit, continent catheterizable reservoir, or orthotopic neobladder utilizing small or large intestine. While radical extirpation of the bladder is often successful from an oncological perspective, there is a significant morbidity associated with enteric interposition within the genitourinary tract. Therefore, there is a great opportunity to decrease the morbidity of the surgical management of bladder cancer through utilization of novel technologies for creating a urinary diversion without the use of intestine. Clinical trials using neourinary conduits (NUC) seeded with autologous smooth muscle cells are currently in progress and may represent a significant surgical advance, potentially eliminating the complications associated with the use of gastrointestinal segments in the urinary reconstruction, simplifying the surgical procedure, and greatly facilitating recovery from cystectomy.

Download full-text


Available from: Matthew Hyndman,
26 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Angiogenesis, which is morphogenesis undertaken by endothelial cells (ECs) during new blood vessel formation, has been traditionally studied on natural extracellular matrix proteins. In this work, we aimed to regulate and guide angiogenesis on synthetic, bioactive poly(ethylene glycol)-diacrylate (PEGDA) hydrogels. PEGDA hydrogel is intrinsically cell nonadhesive and highly resistant to protein adsorption, allowing a high degree of control over presentation of ligands for cell adhesion and signaling. Since these materials are photopolymerizable, a variety of photolithographic technologies may be applied to spatially control presentation of bioactive ligands. To manipulate EC adhesion, migration, and tubulogenesis, the surface of PEGDA hydrogels was micropatterned with a cell adhesive ligand, Arg-Gly-Asp-Ser (RGDS), in desired concentrations and geometries. ECs cultured on these RGDS patterns reorganized their cell bodies into cord-like structures on 50-microm-wide stripes, but not on wider stripes, suggesting that EC morphogenesis can be regulated by geometrical cues. The cords formed by ECs were reminiscent of capillaries with cells participating in the self-assembly and reorganization into multicellular structures. Further, endothelial cord formation was stimulated on intermediate concentration of RGDS at 20 microg/cm(2), whereas it was inhibited at higher concentrations. This work has shown that angiogenic responses can be tightly regulated and guided by micropatterning of bioactive ligands and also demonstrated great potentials of micropatterned PEGDA hydrogels for various applications in tissue engineering, where vascularization prior to implantation is critical.
    Tissue Engineering Part A 10/2008; 15(3):579-85. DOI:10.1089/ten.tea.2008.0196 · 4.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adipose tissue contains a heterogeneous cell population composed of endothelial cells, adipocytes, smooth muscle cells (SMC), and mesenchymal progenitors and stromal cells that meet the criteria put forth by the International Society for Cellular Therapy as defining mesenchymal stem cells (MSC). In this study, we expanded the stromal vascular fraction (SVF) of human adipose tissue and characterized the resulting adherent primary cell cultures by quantitative reverse transcription-polymerase chain reaction, antigen expression, protein fingerprinting, growth kinetics, in vitro tri-lineage differentiation bioactivity, and functional responses to small molecules modulating SMC-related developmental pathways and compared the results to those obtained with functionally validated MSC cultures. SVF-derived initial cultures (P0) were expanded in a defined medium that was not optimized for MSC growth conditions, neither were recombinant cytokines or growth factors added to the media to direct differentiation. The adherent cell cultures derived from SVF expansion under these conditions had markedly distinct phenotypic and biological properties relative to functionally validated MSC cultures. SVF-derived adherent cell cultures retained characteristics consistent with the SMC subpopulation within adipose tissue--phenotype, gene, and protein expression--that were independent of passage number and source of SVF (n=4 independent donors). SVF-derived cells presented significantly less robust in vitro tri-lineage differentiation bioactivity relative to validated MSC. Expanded SVF cells and MSC had opposite responses to the thromboxane A2 mimetic U46619, demonstrating an unambiguous functional distinction between the two cell types. Taken together, these data support the conclusions that SVF cells expanded under the conditions described in these studies are accurately described as adipose-derived SMC and represent a cellular subpopulation of adipose SVF that is separate and distinct from other classes of adipose-derived cells.
    Tissue Engineering Part C Methods 05/2011; 17(8):843-60. DOI:10.1089/ten.tec.2010.0697 · 4.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Different pathological conditions such as congenital organ absence, severe organ injuries, end-stage organ failure and malignancy-related organ removal, have few effective therapeutic options a part from a whole organ transplant, that, however, often meets with a serious shortage of suitable donor organs. The purpose of this paper consists in highlighting what the novel tissue engineering approaches might help to solve such problems. EMERGING CONCEPTS: A recent approach in tissue/organ engineering, particularly to build bioartificial airways, is the procedure of decellularizing a whole donor organ to obtain a complex 3D-biomatrix-scaffold mantaining the intrinsic vascular network, that is subsequently recellularized with recipient's autologous organ-specific differentiated cells or/and stem cells, to build a potentially functional biological substitute. Such strategy has been clinically used to replace organ in trachea/broncus tumor patients. In another approach, mainly used to construct a bioartificial urinary bladder tissue, different types of either biodegradable synthetic polymers or naturally-derived matrices or even polymer/biomatrix-composite materials are used as scaffold for either cell-free or autologous cell-seeded tissue engineering procedures. So far, such technique has been mainly used to make an augmentation cystoplasty in patients with end-stage poorly compliant neuropathic bladder or in exstrophic bladder subjects. Intriguing developments in biomaterial science, nanotechnologies, stem cell biology, and further improvements in bioreactor manufactoring will allow to generate, in the near future, tissue engineered organs that, as for structure/function so the native one-like, might represent the optimum solution to replace organs in tumor surgery.
    European review for medical and pharmacological sciences 03/2013; 17(5):624-31. · 1.21 Impact Factor
Show more