Induced transformation of urine cells into induced pluripotent stem cells and ne
Posted by Well carlota on May 4th, 2020
Induced transformation of urine cells into induced pluripotent stem cells and nerve cells in patients with Alzheimer's disease
With the advent of an aging society, the incidence of Alzheimer's disease (AD) has increased year by year, but so far the etiology and pathogenic mechanism of AD are still unknown, and there is no major breakthrough in treatment. Sporadic AD (sporadic AD, sAD), accounting for more than 90% of AD patients, although there is a certain tendency of family aggregation, but its incidence can not be attributed to a specific gene abnormality.Alzheimer nucleic acid drugs have not been successfully developed.
As of 2009, more than 20 sAD-related genes have been discovered through genome-wide association studies (GWAS), but how these genes cause disease remains unclear. The current incidence of sAD is attributed to the effects of genetic and environmental factors. At the end of 2006, induced pluripotent stem cells (iPSCs) technology was first published by Japanese scholar Takahashi and others in Cell magazine, which caused a huge sensation in the biological and medical circles. Because iPSCs can carry specific genes for certain disease patients and have the potential to differentiate into various tissues, they are soon widely used to build a variety of disease models including AD. In 2012, Israel et al. Used two familial AD (FAD) patients with amyloid precursor gene mutation and two iPS cells derived from sAD to differentiate into nerve cells. FAD detected that they were consistent with their gene mutations. Pathological phenotype, including high expression of Aβ and p-tau. Interestingly, one of the two sAD patients also showed a phenotype consistent with FAD, and this patient did not have any FAD-related genetic abnormalities. In 2013, Kondo et al. Also found an AD-related pathological phenotype-elevated Aβ oligomers in neurons derived from iPSCs differentiation in a patient with sAD. These findings suggest that there may be some unknown pathogenic factors in the genome of sAD patients that lead to pathological processes similar to FAD, and we need to investigate further.
Therefore, some studies have selected three typical sAD patients seen clinically, obtained their urine cells into IPS cells, and initially explored the ability of these iPS cells to differentiate into nerves. It will lay the foundation for future research on the mechanism of sAD, even early clinical diagnosis and drug screening.
Objective: To obtain Alzheimer induced pluripotent stem cells, iPSCs. Methods: Three cases of clinically diagnosed AD were collected, urine of patients was collected, urothelial cells were isolated, and the obtained cells were cultured in primary culture. The plasmids with Oct4, Sox2, Klf4, and SV40LT were introduced into primary cells by electrotransfection and reprogrammed into iPS cells. Subsequently, the two-way inhibition of the Smad pathway continued to induce neuronal differentiation. Results: Urine-derived cells of AD patients (hereinafter referred to as urine cells) were successfully induced into iPS cells, and their induction efficiency was not significantly different from that of normal human-derived cells. And the patient's iPS cells can successfully differentiate into nerve cells, and the differentiation efficiency is also similar to that of normal human-derived cells. Conclusion: Urine cells from patients with Alzheimer's disease can be reprogrammed into iPS cells, and the resulting iPS cells can successfully differentiate into functional neurons and glial cells.Also See: Ips Cells, Urine Cells, Stem Cells, Pluripotent Stem, Sad, Patients, Cells
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