title: Experimental bladder regeneration using a poly-l-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells.
abstract: In the present study, a poly-l-lactide/silk fibroin (PL-SF) bilayer scaffold seeded with allogenic bone marrow stromal cells (BMSCs) was investigated as a potential approach for bladder tissue engineering in a model of partial bladder wall cystectomy in rabbits. The inner porous layer of the scaffold produced from silk fibroin was designed to promote cell proliferation and the outer layer produced from poly-l-lactic acid to serve as a waterproof barrier. To compare the feasibility and efficacy of BMSC application in the reconstruction of bladder defects, 12 adult male rabbits were divided into experimental and control groups (six animals each) that received a scaffold seeded with BMSCs or an acellular one, respectively. For BMSC tracking in the graft in in vivo studies using magnetic resonance imaging, cells were labeled with superparamagnetic iron oxide nanoparticles. In vitro studies demonstrated high intracellular incorporation of nanoparticles and the absence of a toxic influence on BMSC viability and proliferation. Following implantation of the graft with BMSCs into the bladder, we observed integration of the scaffold with surrounding bladder tissues (as detected by magnetic resonance imaging). During the follow-up period of 12 weeks, labeled BMSCs resided in the implanted scaffold. The functional activity of the reconstructed bladder was confirmed by electromyography. Subsequent histological assay demonstrated enhanced biointegrative properties of the PL-SF scaffold with cells in comparison to the control graft, as related to complete regeneration of the smooth muscle and urothelium tissues in the implant. Confocal microscopy studies confirmed the presence of the superparamagnetic iron oxide nanoparticle-labeled BMSCs in newly formed bladder layers, thus indicating the role of stem cells in bladder regeneration. The results of this study demonstrate that application of a PL-SF scaffold seeded with allogenic BMSCs can enhance biointegration of the graft in vivo and support bladder tissue regeneration and function.
authors.affiliation: Department of Cell Culture, Institute of Cytology of the Russian Academy of Sciences (RAS).
authors.forename: Natalia M
authors.initials: NM
authors.lastname: Yudintceva
authors.affiliation: Department of Cell Culture, Institute of Cytology of the Russian Academy of Sciences (RAS); Nanotechnology and Telecommunications, Institute of Physics, Peter the Great St Petersburg Polytechnic University.
authors.forename: Yulia A
authors.initials: YA
authors.lastname: Nashchekina
authors.affiliation: Department of Cell Culture, Institute of Cytology of the Russian Academy of Sciences (RAS).
authors.forename: Miralda I
authors.initials: MI
authors.lastname: Blinova
authors.affiliation: Department of Urology, Federal State Institution Saint Petersburg Research Institute of Phthisiopulmonology, Ministry of Health of Russia.
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Orlova
authors.affiliation: Department of Urology, Federal State Institution Saint Petersburg Research Institute of Phthisiopulmonology, Ministry of Health of Russia.
authors.forename: Alexandr N
authors.initials: AN
authors.lastname: Muraviov
authors.affiliation: Department of Urology, Federal State Institution Saint Petersburg Research Institute of Phthisiopulmonology, Ministry of Health of Russia.
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Vinogradova
authors.affiliation: Department of Urology, Federal State Institution Saint Petersburg Research Institute of Phthisiopulmonology, Ministry of Health of Russia.
authors.forename: Magomed G
authors.initials: MG
authors.lastname: Sheykhov
authors.affiliation: Department of Urology, Federal State Institution Saint Petersburg Research Institute of Phthisiopulmonology, Ministry of Health of Russia.
authors.forename: Elena Y
authors.initials: EY
authors.lastname: Shapkova
authors.affiliation: Department of Urology, Federal State Institution Saint Petersburg Research Institute of Phthisiopulmonology, Ministry of Health of Russia.
authors.forename: Dmitriy V
authors.initials: DV
authors.lastname: Emeljannikov
authors.affiliation: Department of Urology, Federal State Institution Saint Petersburg Research Institute of Phthisiopulmonology, Ministry of Health of Russia; Faculty of Medicine, Federal State Budgetary Institute.
authors.forename: Petr K
authors.initials: PK
authors.lastname: Yablonskii
authors.affiliation: Department of Pathology, Federal State Budgetary Institute "Nikiforov Russian Centre of Emergency and Radiation Medicine" of the Ministry of Health of Russia.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Samusenko
authors.affiliation: Department of Pathomorphology, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Science.
authors.forename: Anastasiya L
authors.initials: AL
authors.lastname: Mikhrina
authors.affiliation: Department of Radiology, Federal Almazov North-West Medical Research Center.
authors.forename: Artem V
authors.initials: AV
authors.lastname: Pakhomov
authors.affiliation: Department of Cell Culture, Institute of Cytology of the Russian Academy of Sciences (RAS); Department of Radiology, Federal Almazov North-West Medical Research Center; Department of Experimental Medicine, First I.P. Pavlov State Medical University of St Petersburg, St Petersburg, Russia.
authors.forename: Maxim A
authors.initials: MA
authors.lastname: Shevtsov
keywords: bladder; bone marrow stromal cells; scaffold; stem cells; superparamagnetic iron oxide nanoparticles; tissue engineering