The use of stem cells especially iPSCs for disease modeling is based on the fact that these cells are capable of self-renewing and that these cells can differentiate into all types of cells of the human body which can be utilized for the preparation of different disease models to study those diseases. Moreover, a patient specific iPSC could be of enormous use as far as development of specific therapeutics regimen/drug is concerned. By combining 3D culture with extracellular matrix proteins, in-vivo microenvironment can be mimicked. iPSCs have helped out in studying various mechanisms that play role in different diseases, a few have been described below.
The following findings from modeling different diseases help out in knowing the molecular mechanisms underlying the disease better, which ultimately carries the work forward to knowing the disease better for the development of a treatment.
Parkinson's Disease (PD) is a very common neurodegenerative disease, in which, dopaminergic neurons of substantia nigra (a structure in mid brain) get lost and formation of Lewy's bodies (inclusions in the cytoplasm of neurons all over the body) occurs. Treatment of this disease had not been possible due to the reason that by the time, Parkinson Disease gets clinically manifested, the neurons have already lost, which makes it very difficult to study the underlying mechanisms of Parkinson disease so as to develop a treatment of it. In such a situation, iPSCs can be used and experiments have also been carried out in this aspect. Devine et al. developed iPSCs from fibroblasts taken from a Parkinson disease affected person possessing triplication of Synuclein gene by the transduction of four basic transcription factors. These iPSCs were then directed to differentiate into dopaminergic neurons in vitro for the study of Parkinson Disease.Another research by Professor Atsushi Takahashi of Kyoto University iPS cell research institute transplanted nerve cells made from human iPS cells to Parkinson's disease monkey on August 30, 2017 claimed to alleviate the Parkinson disease symptom (hand tremor). The research results were published in English Science Journal, Nature (electronic version). The research team created nerve cells that emitted dopamine from iPS cells based of Parkinson's disease patients. This was transplanted into the brain of cynomolgus monkeys reproducing the symptoms of Parkinson's disease. Observing the one year course after transplantation, the symptoms of Parkinson 's disease such as trembling and reduced exercise ability were alleviated over time.
Devine, Michael J., et al. "Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus." Nature communications 2 (2011): 440
Recent preclinical evidence suggests that stem cells can be used to treat or model Alzheimer's Disease. The mechanisms of stem cell based therapies for Alzheimer's Disease include stem cell mediated neuroprotection and trophic actions, anti-amyloidogenesis, beneficial immune modulation, and the replacement of the lost neurons. iPSCs have been recently used to model investigate sporadic and familial Alzheimer's Disease pathogenesis, and screen for anti- Alzheimer's Disease, drugs.
Fan, Xiaotang, et al. "Stem‐Cell Challenges in the Treatment of Alzheimer's Disease: A Long Way from Bench to Bedside." Medicinal research reviews 34.5 (2014): 957-978.
Briggs et al. used iPSCs for the identification of molecular networks that drive the different aspects related to pathogenesis in Down's Syndrome. iPSCs in combination with microarray and RNA sequencing technology, can be used to generate phenotype-genotype maps of complex diseases by linking various defects with phenotypes, like in Down's Syndrome using Chromosome engineering of Down Syndrome-iPSCs
Briggs, James A., et al. "Integration‐free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology." Stem Cells 31.3 (2013): 467-478.
Moad et al. used human prostate and urinary tract cells for the formation of iPSCs and further for studying the mechanisms that regulate the differentiation of prostate and urinary tract cells. With their study, they reported the first successful reprogramming of bladder, prostate and ureter stromal fibroblasts into a pluripotent state and concluded that iPSCs generated from prostate and urinary tract had better efficiency of differentiation to cells of prostate and urinary tract as compared to iPSCs derived from skin fibroblasts which showed that organ of origin plays an important role in terms of efficiency of differentiation.
Moad, Mohammad, et al. "A novel model of urinary tract differentiation, tissue regeneration, and disease: reprogramming human prostate and bladder cells into induced pluripotent stem cells." European urology 64.5 (2013): 753-761.
Other deficiency diseases - Various types of diseases which are caused by some deficiency have been studied by using iPSCs. Park et al. used iPSCs from patients of various diseases like Adenosine Deaminase Deficiency-related Severe Combined ImmunoDeficiency (ADA-SCID), Shwachman-Bodian-Diamond syndrome (SBDS), Gaucher disease (GD) type III for the study of disease models and drug discovery.
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