Abstract
The development of strategies for tissue regeneration and bio-artificial organ development is based on our understanding of embryogenesis. Differentiation protocols attempt to recapitulate the signaling modalities of gastrulation and organogenesis, coupled with cell selection regimens to isolate the cells of choice. This strategy is impeded by the lack of optimal in vitro culture systems since traditional culture systems do not allow for the three-dimensional interaction between cells and the extracellular matrix. While artificial three-dimensional scaffolds are available, using the natural extracellular matrix scaffold is advantageous because it has a distinct architecture that is difficult to replicate. The adult extracellular matrix is predicted to mediate signaling related to tissue repair not embryogenesis but existing similarities between the two argues that the extracellular matrix will influence the differentiation of stem and progenitor cells. Previous studies using undifferentiated embryonic stem cells grown directly on acellular kidney ECM demonstrated that the acellular kidney supported cell growth but limited differentiation occurred. Using mouse kidney extracellular matrix and mouse embryonic stem cells we report that the extracellular matrix can support the development of kidney structures if the stem cells are first differentiated to kidney progenitor cells before being applied to the acellular organ.
Highlights
2 Department of Physiology, University of Toronto, Toronto, Canada 3 Department of Obstetrics and Gynecology, Mount Sinai Hospital and the University of Toronto, Toronto, Canada mouse embryonic stem cells we report that the extracellular matrix can support the development of kidney structures if the stem cells are first differentiated to kidney progenitor cells before being applied to the acellular organ
Ground breaking work demonstrated that rat neonatal kidney cells supported by the extracellular matrix (ECM) of an adult rat acellular kidney resulted in the restoration of kidney function [1]
One of the main hurdles we face in achieving the goal of stem cell derived organs is replicating the three-dimensional structure
Summary
Ground breaking work demonstrated that rat neonatal kidney cells supported by the extracellular matrix (ECM) of an adult rat acellular kidney resulted in the restoration of kidney function [1]. In our study we used acellular adult mouse kidney ECM combined with mouse stem or progenitor cells differentiated to three developmental stages; mesoderm, intermediate mesoderm and metanephric mesenchyme, to determine the mechanical and biological properties of the adult kidney ECM in regards to supporting cell differentiation and survival. Following the recent demonstration of the ability of the ECM from acellular lung to drive the differentiation of ES cell-derived endoderm to mature lung cells led us to investigate if it is possible to decellularize kidneys while maintaining the same level of mechanical and biological support we observed with the lung model [10]. We are able to demonstrate that the adult mouse kidney acellular ECM can support the growth and maturation of mouse embryonic stem cell derived metanephric mesenchyme progenitor cells
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