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Farhat Lab
Farhat Lab

Suitable cells

Since recent research has shown that cell seeding of scaffolds might promote tissue regeneration, we evaluated an innovative cell seeding technique whereby urinary bladder cells were admixed with fibrin glue and sprayed on the acellular matrix (ACM) prior to implantation in a porcine bladder model.

While the fibrin glue proved beneficial in enhancing cellular organization in vitro, central fibrosis of the graft occurred in vivo, suggesting the lack of prompt angiogenesis to support survival of the seeded cells. In this regard many of the patients with urinary bladder pathology do not have competent bladder cells that can be used for tissue engineering. Chambers et al. have demonstrated that cultured cells from the unstable bladder mobilize calcium differently in response to hypotonic stimuli, as compared to cells cultured from the normal bladder. Kropp et al recently showed that neuropathic bladder SMC in culture are significantly different from normal bladder SMC in culture, with elevated cell proliferation, reduced cell adhesion, and cell contractility. Studies from other systems also suggest that cells cultured from diseased tissue, in comparison to cells from normal tissue, retain functional differences in vitro. For instance, Bochaton-Piallat et al. have shown that cultured SMC isolated from the pathologic aorta have a distinctly different phenotype than cultured SMC from the normal aorta. Thus given that cultured neuropathic bladder cells maintain phenotypic and functional differences in vitro, the use of such cells in tissue engineering may result in regeneration of pathologic tissue as opposed to normal tissue.

In hollow organs tissue regeneration such as urinary bladder, smooth muscle regeneration is a crucial requirement to enhance the function of the regenerated tissue with compliance and possible contraction. Therefore, developing an alternative cell source for smooth muscle cells is necessary in order to create a tissue engineered bladder for patients with diseased bladders. It is becoming increasingly clear that within the blood circulate progenitor cells that not only differentiate into hematopoietic cells but also cells that participate in homeostasis, repair and regeneration of solid organs. These circulating cells are flexible, dynamic and capable of differentiating along different lineages, but scarce information is available about the potential of these cells for urinary bladder tissue engineering. For instance, attempts to increase recruitment of the circulating progenitor cells to repair solid organ with the use of growth and chemotactic factors is a plausible strategy to enhance the potential of these cells in regeneration and tissue engineering. However, the intricacies of blood progenitor cell and matrix interactions to promote cellularization of suitable scaffolds in a directed manner are unknown.

We are therefore evaluating the role of the developed biomimetic scaffold (Hyaluronic acid fortified acellular matrix) and SDF-1(a powerful chemo-attractant for BMPCs in the recruitment of BMPC to the scaffold and cellular repopulation of the matrix upon implantation in a mouse model. For this proposal we will be using chimeric bone marrow transplantation to study the role of Utilization of BM cells for the regeneration of the urinary bladder will need much understanding of the molecular mechanism of how the BMPCs are generated and home the urinary bladder, and how we can control and expedite its involvement in the healing phase. Identification of the BMPC population responsible for the regeneration of the biomatrices, and the factors involved in the conduction and amplification of such process is an important step in bladder tissue engineering and its future clinical applications. Clinically, the use of bone marrow derived cells for the regeneration of urinary bladder might be a feasible option for future clinical trial. BM transplantation is a standard part of treatment for many high-risk malignancies in children and this approach could ultimately be incorporated readily into existing paediatric treatment protocols.