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28

28

TH

CONGRESS OF THE ESPU

16:23–16:26

S2-10 (PP)

DETRUSOR BIOENGINEERING USING COMPRESSED

COLLAGEN, ADIPOSE-DERIVED STEM CELLS

AND SMOOTH MUSCLE CELLS

Jakub SMOLAR

1

, Daniel EBERLI

1

, Rita GOBET

2

and Maya HORST

2

1) University Hospital Zurich, Urology, Schlieren, SWITZERLAND - 2) University Children’s Hospital, Division of Pediatric

Urology, Zürich, SWITZERLAND

PURPOSE

The gold standard therapy of end-stage bladder disease refractory to conservative management

is enterocystoplasty, which despite providing functional improvement leads to severe long-term

complications. Therefore, there is a strong clinical need for alternative therapies. The aim of this

study is to develop functional detrusor muscle tissue combining primary and stem cells in hydrogel

scaffolds. 

MATERIAL AND METHODS

Rat bladder smooth muscle (SMC) and adipose-derived stem cells (ADSC) were isolated, ADSC

were pre-differentiated into SMC-like cells (pADSC) and characterized. Cells were combined in

ratios 1:1, 1:2 and 1:3 (SMC:pADSC) and embedded in compressed collagen (CC). After 1, 2 and

3 weeks, cells in scaffolds and 2D in-/direct co-cultures were analyzed for viability, proliferation,

morphology, SMC-marker expression and functionality.

RESULTS

Cell grown in CC showed high viability and proliferation rate. Interconnected microtissues have

developed after 1 week. After 2 weeks, cells in CC showed strong expression of the SMC-markers

calponin, MyH11 and smoothelin. Direct co-culture resulted in significantly increased cellular pro-

liferation. Microtissues consisted of SMC-core surrounded by pADSC. Indirect co-culture resulted

in an increased pADSC survival and ratio-dependent increase in SMC proliferation rate. pADSC

proliferation rate also improved, but remained unaffected by the cell ratio, with 1:1 showing the most

consistent results. SMC-marker expression normalized between the different ratios after 2 weeks of

co-culture and reached almost the SMC monoculture expression levels. 1:1 co-culture contracted

similarly to the control and significantly better than other ratios.

CONCLUSIONS

We have shown that a SMC–pADSC co-culture results in an improved cell survival, proliferation,

microtissue formation without any significant changes in phenotype and functionality. The combina-

tion of SMC and pADSC with CC may help to engineer functional detrusor muscle tissue by solving

the major issues of tissue engineering, namely poor cell survival, proliferation, functionality and

phenotype instability.