Dataset Information

Composition and immune environment of urinary bladder matrix scaffolds

ABSTRACT: Urinary bladder matrix (UBM) is used clinically for treatment of diabetic ulcers, abdominal wall reconstruction, soft tissue filling among other applications. Composed mainly of collagen, the material is a mix of fibrous collagen structures and sheet-forming structures characteristic of the urinary bladder matrix basal lamina. Upon application of a biomaterial in a traumatic or non-traumatic setting, there is a cascade of immune cells that react to the damaged tissue and biomaterial. Here, through the use of multicolor flow cytometry, we describe the various cells that infiltrate the UBM scaffold in subcutaneous and volumetric muscle injury model. A wide variety of immune cells are found in the UBM scaffold immune microenvironment (SIM) including F4/80 + macrophages, CD11c + dendritic cells, CD3 + T cells and CD19 + B cells. UBM induced a systemic IL-4 upregulation and a local M2-macrophage response. The recruitment and activation of these cells is dependent upon signals from the scaffold and communication between the different cell types present.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Sus Scrofa Domesticus (domestic Pig)

SUBMITTER: Akhilesh Pandey

LAB HEAD: Jennifer H. Elisseeff

PROVIDER: PXD005400 | Pride | 2017-06-09

REPOSITORIES: pride

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Publications

Proteomic composition and immunomodulatory properties of urinary bladder matrix scaffolds in homeostasis and injury.

Sadtler Kaitlyn K Sommerfeld Sven D SD Wolf Matthew T MT Wang Xiaokun X Majumdar Shoumyo S Chung Liam L Kelkar Dhanashree S DS Pandey Akhilesh A Elisseeff Jennifer H JH

Seminars in immunology 20170201

Urinary bladder matrix (UBM) is used clinically for management of wounds and reinforcement of surgical soft tissue repair, among other applications. UBM consists of the lamina propria and basal lamina of the porcine urinary bladder, and is decellularized as part of the process to manufacture the medical device. UBM is composed mainly of Collagen I, but also contains a wide variety of fibrillar and basement membrane collagens, glycoproteins, proteoglycans and ECM-associated factors. Upon applicat ...[more]

PMID: 28583764

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Project description:To date, there are no efficacious translational solutions for end-stage urinary bladder dysfunction. Current surgical strategies including urinary diversion and bladder augmentation enterocystoplasty (BAE) utilize autologous intestinal segments (e.g. ileum) to increase bladder capacity to protect renal function. Considered the standard of care, BAE is fraught with numerous short- and long-term clinical complications. Previous clinical trials employing tissue engineering approaches for bladder tissue regeneration have also been unable to translate bench-top findings into clinical practice. Major obstacles still persist which need to be overcome in order to advance tissue engineered products into the clinical arena. These include scaffold/bladder incongruencies, the acquisition and utlity of appropriate cells for anatomic and physiologic tissue recapitulation, and the choice of appropriate animal model for testing. Here we demonstrate that the elastomeric, bladder biomechanocompatible poly(1,8-octamethylene-citrate-co-octanol) (PRS; synthetic) scaffold co-seeded with autologous bone marrow-derived mesenchymal stem cells (MSCs) and CD34+ hematopoietic stem/progenitor cells (HSPCs) supports robust long-term, functional bladder tissue regeneration within the context of a clinically relevant baboon bladder augmentation model simulating bladder trauma. Partially cystectomized baboons were independently augmented with either autologous ileum or stem cell-seeded small intestinal submucosa (SIS; a commercially available biological scaffold) or PRS grafts. Stem cell synergism promoted functional tri-layer bladder tissue regeneration including whole graft neurovascularization in both cell-seeded grafts. However, PRS-augmented animals demonstrated fewer clinical complications and more advantageous tissue characterization metrics compared to ileum and SIS-augmented animals. Two-year study data demonstrate that PRS/stem cell-seeded grafts drive bladder tissue regeneration and are a suitable alternative to BAE.

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