Abstract

Recent advances in renal tissue engineering have shown that dissociated, early renogenic tissue from the developing embryo can self-assemble into morphologically accurate kidney-like organs arranged around a central collecting duct tree. In order for such self-assembled kidneys to be useful therapeutically or as models for drug screening, it is necessary to demonstrate that they are functional. One of the main functional characteristics of mature kidneys is transport of organic anions and cations into and out of the proximal tubule. Here, we show that the transport function of embryonic kidneys allowed to develop in culture follows a developmental time-course that is comparable to embryonic kidney development in vivo. We also demonstrate that serially-reaggregated engineered kidneys can transport organic anions and cations through specific uptake and efflux channels. These results support the physiological relevance of kidneys grown in culture, a commonly used model for kidney development and research, and suggest that serially-reaggregated kidneys self-assembled from separated cells have some functional characteristics of intact kidneys.

Highlights

  • Transport of organic anions and cations in murine embryonic kidney development and in serially-reaggregated engineered kidneys

  • The 376 Dalton fluorescein derivative 6-CF has been shown to be transported by organic anion transporters (Oats)[9,10,11,12]

  • Uptake of organic anions in mice is mediated by organic anion transporters localized to both the basolateral (Oat1/ 3 and Oatp4c1) and apical surfaces (Oat2/5)[5,16,17]

Read more

Summary

Introduction

Transport of organic anions and cations in murine embryonic kidney development and in serially-reaggregated engineered kidneys. We demonstrate that serially-reaggregated engineered kidneys can transport organic anions and cations through specific uptake and efflux channels These results support the physiological relevance of kidneys grown in culture, a commonly used model for kidney development and research, and suggest that serially-reaggregated kidneys self-assembled from separated cells have some functional characteristics of intact kidneys. At embryonic day 11.5 (E11.5), the rudimentary kidney is composed of two distinct tissue types, the epithelial ureteric bud surrounded by condensed mesenchyme Previous work in this laboratory has shown that kidney rudiments at this stage can be dissociated into a single cell suspension, and these cells can self-assemble into organotypic renal structures[1]. All assays are with live cultured embryonic kidneys and imaging is carried out on live kidneys or serial reaggregates

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call