Poster Presentation 6th Annual Meeting for Australasian Society for Stem Cell Research 2013

MSC-like cells derived from renal epithelial origin demonstrate specific differentiation and integration capacity (#138)

Joan Li 1 , Norseha Suhaimi 1 , Usukh Ariunbold 1 , Minoru Takasato 1 , Nana Sunn 2 , Melissa Little 1
  1. University of Queensland, Brisbane, QLD, Australia
  2. Diamantina Institute, University of Queensland, Brisbane, Australia

We have previously described an endogenous renal MSC-like population in the mouse kidney. While demonstrating an immunophenotypic and differentiative capacity similar to bone marrow (BM) MSCs, this renal MSC-like population showed specific gene expression suggesting a collecting duct location. Here we sought to confirm the location and properties of this population. Enrichment for collecting duct epithelium was performed by FACS sorting from adult Hoxb7/GFP mice. This population gave rise to MSC-like cells expressing all typical MSC surface markers. When cultured in a 3-D system, these cells formed epithelial structures expressing E-cadherin. Microinjection of these MSC-like cells into the neonatal (day 1) kidney under ultrasound guidance demonstrated specific integration into Aqp2+ collecting ducts confined to the inner medulla / papillary region. In contrast, epithelial integration was never observed after microinjection of GFP+BM MSCs. While Hoxb7 is regarded as collecting duct-specific, temporal and spatial analysis of Hoxb7expression revealed an interstitial GFPlo population arising shortly after birth which peaked (4.6% of total cells) at day 5 before disappearing in the adult kidney. QPCR of this Hoxb7lo population revealed co-expression of characteristic interstitial (Wnt4+Pod1+NG2+) and collecting duct epithelial (Ecad+Hoxb7+) markers suggesting a phenotype intermediate between interstitium and epithelium. We are now investigating whether this subpopulation undergoes a neonatal mesenchyme-to-epithelial event to give rise to the MSC-forming components of the adult collecting duct. In conclusion, an endogenous MSC-like population can be derived from the mature collecting duct epithelium of the kidney. These are capable of epithelial differentiation in vitro and specific integration into the neonatal collecting duct in vivo via mesenchymal-to-epithelial transition. Further in vivo experiments will examine whether these cells play a role in normal tissue turnover as well as assist in the treatment of renal damage and disease.