(790g) Determining the Effects of Adipose-derived Exosomes on Stem Cell Proliferation and Adipogenesis

Determining the Effects of
Adipose-derived Exosomes on Stem Cell Proliferation and Adipogenesis

The field of
tissue regeneration has made many strides to improve therapeutic methods and
restore missing functions to patients with the introduction of stem cell
therapies. Transplantation of fat tissue has provided beneficial metabolic
effects to patients by supplying sufficient vascularization and innervation¹.
Despite the benefits that adipose tissue therapeutics provide, there persists
limitations such as the restriction to autologous therapies due to immunogenic
responses. Exosomes may serve as a novel cell-free method to provide the same
therapeutic properties while circumventing potential immunogenic responses.
This is beneficial to patients who are deficient in fat content and would not
have tissue for an autologous therapy, such as lean and pediatric patients. The
purpose of this project is to determine the therapeutic potential of
adipose-derived exosomes on tissue regeneration and their influence on human
adipose-derived stem cell (hASC) adipogenesis.

                Exosomes
are small vesicles (40-100nm) that are secreted by a variety of cell types into
the extracellular matrix. Within an apoptotic cell, the intracellular matrix
fuses with the plasma membrane to produce multivesicular bodies (MVB). Through
fusion with the plasma membrane, exosomes retain the properties that are
associated with the native cell. These vesicles have surface ligands that help
to facilitate cell-to-cell interactions without the need for direct cell
contact. By inducing the expression of target growth factors, we can interact
with the various surface proteins that are involved in cell proliferation and differentiation².
Exosomes fuse with target cells to exchange membrane proteins and cytosol to
signal intended functions³.
The surface proteins of cells provide a more accessible route for communication
than internal targets. Transcription factors that have been found to induce
adipogenesis include members of the CAAT/enhancer binding protein (C/EBP) and
peroxisome proliferatoractivated receptor (PPAR) families (Figure 1). Through a
combination of interactions, each transcription factors can directly or
indirectly activate the expression of adipogenesis. C/EBPβ and C/EBPδ
have synergistic effects to influence PPARγ and C/EBPα, each of which
have a direct influence on gene expression. PPARδ also has a direct
influence on adipocyte gene expression, with slightly less significance⁴.

By directing
the surface interactions, it is possible to have a cell perform specific tasks,
in response to the given environment. I
hypothesize that adipose-derived exosomes can serve as a therapeutic agent by
promoting proliferation and differentiation.

Currently,
exosomes from differentiating human skeletal muscle cells have been tested to
observe the regenerative properties within skeletal muscle tissue. Studies in other
tissues have also shown that mesenchymal stem cells (MSC) derived exosomes have
functions such as repairing tissue damage, suppressing inflammatory damage, and
modulating the immune system⁵.
Working with adipose-derived tissue, I want to determine the therapeutic
potential that exosomes possess. Future work will consist of determining the
mechanism behind each function. This therapy has the potential to assist with
tissue regeneration in patients that are dealing with adipose tissue defects.
Exosomes show promise for transferring regenerative therapeutics between
patients without having to encounter immunogenic rejection, a major setback
when dealing with stem cells. This research will open new avenues for dealing
with patients who lack the tissue mass for autologous regeneration therapeutics
such as lean or pediatric patients. Restoring functions to damaged organs can
one day be achieved by mediating the repair of the desired tissue through
exosome mediated cell-to-cell signaling.