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Applications of 3D bioprinted iPSCs
attention, and memory [120] . All major nerve cell 4.3.2.3 Amyloid lateral sclerosis (ALS)
types can be differentiated from iPSCs and can be ALS is the most prevalent motor neuron (MN)
cultured in complex conditions, which mimic the disease characterized by the progressive loss of the
AD conditions. Precise Genome editing techniques upper and lower MNs, leading to muscular atrophy,
can be used to introduce or correct AD-linked paralysis, and death within 5 years after the first
mutations to examine phenotypes in isogenic diagnosis [130] . The iPSC-derived disease models of
backgrounds cells . It has become increasingly ALS showed increased oxidative stress and DNA
[14]
clear in recent years that multiple different brain damage in neurons. ALS specific mutations and
cell types can contribute to AD progression [121] . altered transcriptome profile were also noticed
Thus, examining their interactions and impacts on in the iPSC models. Osborne et al. reported the
each other are of critical importance. The iPSCs effectiveness of the small molecule vardenafil, in
can be differentiated into neural crest or neural regaining the resilience of MNs by regulating the
progenitor cells, which can subsequently be insulin-like growth factor-II signaling in an iPSC-
patterned to different neuron subtypes including derived ALS model [132] . Researchers created 3D
glutamatergic, GABAergic, cholinergic, and bioprinted ALS disease model using iPSC-derived
dopaminergic neurons [122-124] . 3D bioprinted AD MNs from a patient with TDP-43 gene mutation.
models will facilitate the development of effective TDP-43 gene mutation causes sporadic ALS.
therapeutics to combat AD-induced dementia. Bioprinted iPSC derived autologous tissue models
Moreover, bioprinted AD tissue models can serve of ALS disease serve as a valuable tool for studying
as a more humanized model system for AD drug the disease pathology as well as aid in the screening
testing, as many drugs tried in experimental of personalized drugs against the disease [133] .
animals failed in clinical trials due to species
variability [125,126] . 4.3.3 Bioprinted iPSCs in oncology
4.3.2.2 Parkinson’s disease (PD) The iPSCs derived from cancer tissues present a
range of new opportunities for the study of human
PD is the second most common neurodegenerative cancer. If human cancer cells were converted to
disorder [127] . Studies using iPSC-derived pluripotency and then allowed to differentiate
dopaminergic neurons from patients with back into specific cancer tissue, they might shed
monogenic and sporadic PD have successfully light on the early stages of cancer [134] .
illustrated key features of PD pathophysiology, Although 3D printing was developed decades
including impaired mitochondrial function, ago, recent times witnessing a huge jump in
increased oxidative stress, and accumulation of adapting this versatile technology to the field of
α-synuclein protein, namely, Lewy bodies [128] . cancer modeling by fabricating sophisticated
Using iPSC-derived dopaminergic neurons biological structures typical to cancer tissues.
from PD patients with mutations in the disease The cancer cells could be isolated from surgically
causing genes, many investigators have drawn removed cancer tissues. The isolated tumor
mechanistic insights on how mutations of these cells are reprogrammed to pluripotent state by
genes are linked to PD. Coculturing glial cells and introducing the four transcription factors Oct4,
neurons both derived from iPSCs of PD patients Sox2, Klf4, and c-myc using a suitable method.
should therefore be another platform to advance The colonies are grown for a period of 2 – 4 weeks
insights into the multifactorial pathogenesis of PD. and cells with pluripotent stem cell morphology
Bioprinted dopaminergic neurons can be treated and molecular characters are expanded to create
with neurotoxins such as 6-hydroxydopamine, specific cancer iPSC lines [135] . These lines are
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, differentiated into the tumor cell type of origin.
paraquat, and rotenone to induce PD like syndrome The iPSC-derived differentiated cells could
to study PD pathogenesis [129-131] . be then bioprinted into tumor tissues which

68 International Journal of Bioprinting (2020)–Volume 6, Issue 4