The Sharma laboratory explores aspects of tissue engineering technology related to the regeneration of functional bladder tissue. Clinically, the gold standard for repair of a diseased or injured bladder is enterocystoplasty – i.e., augmentation with a piece of bowel. While this can restore partial urinary function and prevent more serious disease, patients may have metabolic imbalances and may be required to self-catheterize for the rest of their lives.
The goal of this research is to develop a tissue-engineered replacement for bladder tissue that restores regular urinary function while avoiding the issues associated with bowel augmentation.
Current Research Projects
Scaffolding for Cells
One aspect of our research involves investigating the impact of scaffolding on tissue regeneration. We have previously investigated subintestinal submucosa (SIS), which is a biologically-derived decellularized matrix taken from porcine tissue. SIS provides an environment for cell infiltration which is very similar to native extracellular matrix (ECM). Many of the native growth factors and structural proteins are retained after SIS processing. We, along with many other researchers, have demonstrated the potential for bladder tissue repair using SIS.
We have shown that human mesenchymal stem cells seeded onto elastomeric thin films supported partial regeneration of bladder tissue in a rat augmentation model.
A vital aspect of tissue regeneration is the quality of the cells that are used to form the neotissue. In a classic tissue engineering model, cells adjacent to the site of injury are expanded in vitro until they can be seeded with sufficient density onto a porous scaffold. However, when tissue injury is due to disease (e.g., for a neuropathic bladder), the surrounding cells may also be unsuitable for creating a normal healthy tissue. Similarly, when tissue injury is due to trauma, the cells expanded in vitro may express a proliferative phenotype after seeding onto the scaffold when in fact another phenotype may be preferable.
To address these issues, our laboratory is examining alternative cell sources for bladder engineering and developing methods internally for better characterization of these cells. In particular, we have been working with smooth muscle cells derived from the ureter. Ureter and bladder tissues form from different embryologic layers during development, and we hypothesize that the diseased state of a neuropathic bladder may not be shared with a ureter from the same patient.
We also have a strong interest in exploring the role of stem cells in bladder repair, both in their recruitment to a site and their differentiation upon arrival. Bone marrow-derived cells and other pluripotent cell types may be preferable for creating tissues that more accurately reproduce a healthy functioning bladder.