Organ Regeneration Based on Developmental Biology

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9.8 Applications Toward the Disease Modeling

It is now possible to effectively induce metanephric nephron progenitor cells from
a stem cell population. Further, the three-dimensional structure of the kidney—
including both the glomerulus and the renal tubule—can be reconstructed. Therefore,
it is feasible that patient-derived iPS cells could be used to produce disease-specific
renal tubules and podocytes that could be applied in the treatment of renal diseases
and the development of novel drugs. Indeed, recent reports have described the par-
tial reproduction of nephric tubule injury. For example, apoptosis or the expression
of KIM1 has been detected following application of the nephrotoxic drug cisplatin
to induced kidney tissue in  vitro (Takasato et  al. 2015 , Morizane et  al. 2015 ,
Freedman et al. 2015 ). However, to fully replicate physiological disease dynamics,
it may be essential to induce blood perfusion into the induced kidney tissue.

9.9 Future Directions Toward Creation of Functional

Kidneys

The kidney functions by filtering blood to produce urine. Therefore, a continuous
blood supply, a filtration unit (nephron), and a drainage system are essential for
renal function. Generation of functional renal tissues will require replication of the
physiological interactions that occur between innate kidney precursors, i.e., the UB,
nephron progenitors, stromal cells, and the endothelia (see 1.2.1). Most reports to
date have focused on the selective induction of nephron components via the nephron
progenitors and have required coculture with Wnt-producing cells or administration
of Wnt analogues to induce formation of epithelialized nephron structures. Because
these differentiation signals deplete the supply of uninduced nephron progenitors,
they disrupt the continuous propagation of nephron structures as seen in vivo (see
1.2.2). Additionally, induced nephron structures within the tissue are not connected
to each other via the collecting duct system and hence cannot excrete urine outside

Table 9.1 (continued)

Gene

Symbol Gene name

iPS-derived

podocytes

Human

glomeruli

Mouse

podocytes

CTNNAL1 Catenin (cadherin-associated protein),

alpha-like 1

2.66 2.13 5.97

COL4A4 Collagen, type IV, alpha 4 2.57 1.60 4.42

ITGAV Integrin, alpha V 2.43 4.59 3.16

COL4A5 Collagen, type IV, alpha 5 2.13 11.05 2.51

SYNPO Synaptopodin 2.07 19.26 7.40

9 Early Kidney Specification and Its Recapitulation by Pluripotent Stem Cells