48

Bioinformatics of the Brain

approach “biological or cellular time machines” since they take us back to the

stem cells lost in the embryonic ages of an individual. Since their discovery,

many pieces of evidence have accumulated rapidly that exhibit how iPSCs

are indistinguishable from ESCs in terms of differentiation capacity, differ-

entiation range, self-renewal, spatiotemporal gene expression landscape, and

epigenetic profile [27]. Thereby, iPSCs have eliminated the biological, ethi-

cal, and legal limitations because the acquisition methods of iPSCs do not

interfere with a living embryo.

Conventional transgene delivery-based iPSC production methods have

been reported to cause two main issues: tumorigenicity due to oncogene activa-

tion and low efficiency due to insufficient induction of genetic/epigenetic pro-

grams. These limited the usage and biological safety of iPSCs in clinical trials.

However, recent advances such as transgene-free chemical cocktails, non-viral

episomal vectors, miRNA delivery, and auto-erasable and replication-defective

Sendai virus (SeVdp) has decimated the highlighted problems and mediated

the production of clinical-grade human iPSCs [28].

As indicated, iPSCs can conveniently differentiate into various somatic cell

types, particularly NSCs, neurons, MSCs, osteocytes, hematopoietic cells, fi-

broblasts, cardiac cells, pancreatic cells, epithelial cells, etc., by gaining whole

cell-specific biological functions in vivo [29, 30]. Besides, somatic cell repro-

gramming lets us manufacture individual-specific embryonic-like stem cells

(referred to as iPSCs) from the somatic cells, most of which are easily acces-

sible through non-invasive methods. When altogether considered, iPSCs have

come to the forefront as marvelous cellular tools for multi-task applications

involving personalized disease-specific cellular therapies, tissue engineering,

disease modeling, drug screening, studying developmental aspects, and so on

[31]. Clinical trials in different phases continue to increase with each passing

day. In total, 153 clinical studies, covering imprinted disorders, cardiovascular

diseases, visual impairments, autoimmune diseases, and neurological defects,

have been listed with promising outcomes in the NIH Clinical Trial database

[32]. Likewise, iPSCs have been reported as feasible tools for allogenic and

autologous transplantation strategies in neurodegenerative diseases [33].

2.3

Experimental and Clinical Attempts at Stem Cell

Usage in Neurodegenerative Diseases

Various stem cell types are used for several clinical and research purposes

within the context of neurodegenerative diseases. Certain objectives that stem

cells facilitate are summarized in Table 2.1. While clinical trials are under con-

sideration in different phases, basic research provides worthwhile knowledge.

Significant insights are then progressed into translational studies that bridge

the gap between basic and clinical research.