IBNAM Investigator Focus

Earl Cheng MD FAAP
The Cheng laboratory studies mechanisms for bladder regeneration through tissue engineering. Developmental issues may lead to bladder malformation or poor innervation, resulting in a dysfunctional bladder with low storage capacity and high internal pressures. Surgeons currently use of a patient's own intestinal tissue to expand this capacity, but this can have substantial side effects such as eventual perforations, stones, or tumor formation. Traditional bladder engineering uses either conventional PGA/PLGA biodegradable polymeric scaffolds, or commercially-available biologically-derived scaffolds, such as SIS. Both of these are usually seeded with a patient's own smooth muscle cells. Our laboratory is investigating next-generation scaffolds and cell sources for bladder engineering. We examine scaffolds with nanoscale functionality for cell signaling, growth factor delivery, or drug release. We are also investigating a wide range of stem cell sources for seeding scaffolds, especially for cases in which the existing smooth muscle may be inherently diseased.
	Immunostaining of a bladder cross-section. Large a -SMA+ smooth muscle bundles are visible at the right, while the thin, folded layer of urothelium is visible at the left. These two layers communicate during development, and our lab aims to reproduce both for functional bladder restoration. (nuclei: blue; a -SMA: red)


From: Beqaj, SH; Donovan, JL; Liu, DB; Harrington, DA; Alpert, SA; Cheng, EY; "Role of Basic Fibroblast Growth Factor in Neuropathic Bladder Phenotype" J Urol 2005; 174:1699-1703.
A strong mitogenic effect of basic fibroblast growth factor (bFGF) was shown for both normal (white bars) and neurogenic (shaded bars) bladder SMCs. Cells were treated with bFGF and/or a neutralizing anti-bFGF antibody. These studies demonstrate the impact of bFGF on SMCs in the bladder, and make it a key target for further research. Asterisks indicate p<0.001 for 3 samples. Error bars show a +/- 95% confidence interval.

Cross sections of a PGA scaffold, seeded with human bladder smooth muscle cells. (a) and (c) are scaffolds coated with a branched-lysine peptide amphiphile molecule, bearing an RGDS epitope; (b) and (d) are bare PGA scaffolds. Both the Masson's trichrome staining (top) and scanning electron microscopy (bottom) show greater SMC adhesion to the coated scaffolds than to the bare ones.	From: Harrington, DA; Cheng, EY; Guler, MO; Lee, LK; Donovan, JL; Claussen, RC; Stupp, SI; "Branched peptide-amphiphiles as self-assembling coatings for tissue engineering scaffolds" J Biomed Mater Res 2006; 78A:157-167

From left to right: Dan Harrington, Partha Hota, Earl Cheng, Natalie Fuller, Arun Sharma, and Hatim Thaker
From left to right: Dan Harrington, Earl Cheng, Ryan Sullivan, Jane Lewis, Jena Donovan, Brad Erikson, and Arun Sharma