Therapeutic Potential of Stem Cells in Neurodegenerative Diseases

47

regeneration in adults. Conversely, the curation of neurodegenerative disorders

also passes through neural stem cells, as reviewed in the following sections.

2.2.2.3

Hematopoietic Stem Cells (HSCs)

Hematopoietic stem cells (HSCs) are another multipotent progenitors within

the human body that compose all blood cell types. HSCs mostly reside in

various fetal and adult niches, including the fetal liver, umbilical cord, bone

marrow, and peripheral circulation in humans [19]. HSCs go through a se-

ries of multistep differentiation processes that result in the generation of

all hematological cells, called hematopoiesis. Initially, HSC (hemocytoblast)

commits into common lymphoid progenitor (CLP) or common myeloid pro-

genitor (CMP) in adult bone marrow. After CLPs further differentiate into

lymphoblasts, precursors of natural killer (NK) cells, T lymphocytes, and B

lymphocytes emerge. Then precursor cells complete their maturation process,

in particular, hematopoietic tissues [20]. On the other hand, CMPs gradually

branch into lineage-specific subfractions (MEPs and GMPs) with commit-

ted cell fate decisions. These subfractions then pursue their ripening steps in

specific areas. Finally, granulocytes and monocytes (from myeloblasts), ery-

throcytes (from proerythroblasts), and platelets (from megakaryoblasts) arise

from related precursors in a stepwise manner [21].

HSCs have been safely used as the best remedial sources for numerous

hematological diseases and cancers in humans since the first allogenic HSC

transplantation was practiced by Edward Donnall Thomas, a Nobel Laureate,

in 1957 [22]. The rationale behind allogenic and autologous HSC transplan-

tation is to ameliorate impaired hematopoiesis and the immune system by

replacing defective HSCs with healthy or conditioned ones. Similar to MSCs,

a huge number of HSC transplantations and clinical trials have been increas-

ingly proceeding [23].

2.2.3

Induced Pluripotent Stem Cells (iPSCs)

Shinya Yamanaka (Nobel Laureate in 2012) and coworkers launched a ground-

breaking milestone in the field of stem cells in 2006, proving terminally

differentiated somatic cells could be reprogrammed back to the pluripotent

state. Moreover, these induced pluripotent stem cells (iPSCs) that originated

from human and mouse fibroblasts in laboratory conditions surprisingly re-

possessed all embryonic-like stem cell characteristics [24, 25]. Methodologi-

cally, ectopic overexpression of Oct4, Sox2, Klf4, and c-Myc (OSKM), a set

of pluripotency-related transcription factors (Yamanaka’s factors), together

are able to recover ESC-like features through the reinduction of a master

transcriptional regulatory network (somatic cell reprogramming). Above all,

it also orchestrates the reprogramming of the epigenetic landscape, includ-

ing the global DNA methylation profile, histone modification hallmarks, and

miRNA expression levels, back to the pluripotent state [26, 27]. Thus, it would

not be considered wrong to call iPSCs and/or somatic cell reprogramming