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発表内容

Title:
Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney.

Minoru Takasato, Ph.D.
Institute for Molecular Bioscience, The University of Queensland , Brisbane , Australia

Abstract:
With the prevalence of end-stage renal disease rising 8% per annum globally, there is an urgent need for renal regenerative strategies. The kidney is a mesodermal organ that differentiates from the intermediate mesoderm (IM) through the formation of a ureteric bud (UB) and the interaction between this bud and the adjacent IM-derived metanephric mesenchyme (MM). The nephrons arise from a nephron progenitor population derived from the MM. The IM itself is derived from the posterior primitive streak. Although the developmental origin of the kidney is well understood, nephron formation in the human kidney is completed before birth. Hence, there is no postnatal stem cell able to replace lost nephrons. We have successfully directed the differentiation of human embryonic stem cells (hESCs) through posterior primitive streak and IM under fully chemically defined monolayer culture conditions using growth factors used during normal embryogenesis. This differentiation protocol made the synchronous induction of elongating epithelial structures of UB and non-epithelial cell population of MM that surrounded UB structures. These two types of kidney progenitors resulted in the renal vesicle formation, the first event of nephrogenesis. Furthermore, 3D culture environment allowed for forming self-organizing structures, including nephron formation, in vitro . Such hESC-derived components show broad renal potential ex vivo , illustrating the potential for pluripotent-stem-cell-based renal regeneration. In summary, we reported the successful differentiation of pluripotent cells to a self-organizing kidney. The coordinated induction of cells from the various key cellular populations involved in kidney development demonstrates the requirement for interacting niches for the creation of complex morphogenetic structures. The capacity for such populations to undergo self-organization in vitro bodes well for the future of tissue/organ bioengineering.

References:
Takasato, M, Er, PX, Becroft, M, Vanslambrouck, JM, Stanley , EG, Elefanty, AG, Little, MH. Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. Nature Cell Biology 16:118-26 (2014).

Takasato, M, Maier, B, Little, MH. Recreating kidney progenitors from pluripotent cells. Pediatric nephrology (2013)