Page 48 - GPD-3-2
P. 48
Gene & Protein in Disease β-cell regeneration and stem cell niche
aspect of this signaling system. For instance, many GPCRs before transplantation would considerably broaden the
and heterotrimeric G proteins, in addition to pathways utility of this stem cell source. While stem cell expansion
such as hedgehog, hippo, and prostaglandins signaling, can also be achieved in vivo following the revascularization
interact with tumor progression and are frequently of the transplanted cells, this strategy may present
implicated in cancer. Despite this understanding, the greater risks than ex vivo expansion unless the growth
precise role of the GPCRs in interpreting environmental, stimuli employed in vivo are carefully controlled. The
58
dietary, and microbiome signals to regulate epithelial stem attractiveness of ex vivo stem cell expansion lies in the
cell fate is an enthralling yet understudied topic. A deeper precise definition of culture conditions and the ease with
understanding of the specific GPCRs, their signaling which transitory modification of regulatory pathways can
partners, and the cellular mechanisms involved will be be exploited in vitro. However, this strategy has proven to
crucial for developing therapeutic strategies targeting be quite difficult because complete stem cell proliferation
intrinsic stemness pathways associated with malignant requires symmetric self-renewal divisions of HSCs, where
transformation and tumor growth. GPCR signals exert both daughter cells retain HSC characteristics. In vitro-
a long-lasting influence on the fate of epithelial stem grown HSCs typically divide asymmetrically, producing
cells, transiently and simultaneously activating multiple one HSC and one more differentiated progenitor cell,
pathways that desensitize receptors and halt intracellular or symmetrically, producing two progeny cells that are
cascades. Therefore, a comprehensive comprehension of no longer capable of becoming HSCs. The equilibrium
54
the interactions between GPCR signaling, transcriptional between HSC proliferation and quiescence is ultimately
regulation, and cellular differentiation will shed light maintained by positive and negative regulators. 59
on the processes that maintain stem cell characteristics Activating pathways that promote HSC self-renewal
and the strategies employed by stem cells to adapt to and/or inhibit those that lead to HSC quiescence,
microenvironmental alterations. In the body, the differentiation, or apoptosis should be a key component
55
epidermis serves as a protective barrier against external of stem cell expansion efforts. Recent advancements
environmental aggressors, microbial invasion, and in understanding stem cell self-renewal mechanisms
other threats. The basal layer of the epidermis harbors have enabled the development of new techniques for
proliferating, immature ESCs, while multiple layers of expanding stem cells, some of which require viral
differentiated, non-proliferating suprafacial cells constitute vector-mediated gene transfer for effective growth. For
60
the upper layers. safety, it is ideal that the vectors induce transitory gene
Cornified cells from the outer layer are continually expression and are non-integrating. Secure methods for
replenished through the mitotic activity of ECSs, requiring a stem cell expansion often use soluble components such
delicate balance between self-renewal and differentiation in as cytokines, developmental cues, or angiopoietin-like
the adult epidermis to maintain epidermal homeostasis and (Angptl) proteins. Jagged, a soluble version of the Notch
a functional barrier. Extensive research has been dedicated ligand, promotes the expansion of severe combined
to understanding how ESCs respond to the demands of immunodeficient repopulating cells, making it a
tissue growth and homeostasis, as well as the regulatory potential tool for ex vivo stem cell expansion. However,
mechanisms orchestrating these changes. This section the most promising soluble factors for murine HSC
49
discusses recent research on the regulation of the ESC during growth identified to date are the Angptl proteins. Angptl
development and their dynamics in adult homeostasis, proteins may prove useful for future cell and gene therapy
arguing that the microenvironment solely dictates the fate techniques if they can increase human HSCs as effectively
of hematopoietic stem cells (HSCs). Instead, intrinsic and as they do in the mouse system. Fibroblast growth factors
environmental signals collaboratively affect HSC behavior. are also particularly important to highlight because they
The concept of the stem cell niche integrates these aspects have been proven to support and preserve the primitive
into a more comprehensive and holistic framework. For phenotype of murine HSCs in culture. 61
patients in need of blood and marrow transplants, the search It should be underlined that studies in mice have
for donors with appropriate histocompatibility antigens provided most of our knowledge concerning stem cell
can frequently pose significant challenges. Cord blood growth. Mouse and human stem cells differ in cytokine
56
(CB) cells, now widely available and containing various receptors, proliferative potential, and telomere biology,
histocompatibility gene haplotypes, are increasingly being leading to both differences and parallels in strategies for
recognized as a valuable source of human stem cells. 57 increasing HSCs. Nephroblastoma overexpressed should
Since there are only a limited number of HSCs in each be considered for clinical stem cell growth techniques, as
CB sample, the capacity to grow CB stem cells ex vivo it can expand primitive HSCs. Small molecule medications
Volume 3 Issue 2 (2024) 12 doi: 10.36922/gpd.2996

