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Stem
cell research has the potential to benefit millions of people
around the world requiring replacement or renewal of tissue
function. Stem cells are unspecialized, multi-potential cells
with the ability to self-renew indefinitely, and differentiate
into more mature cells with specialized functions. The bone
marrow contains at least two kinds of stem cells, the hematopoietic
stem cells and bone marrow stromal cells (mesenchymal stem
cells). An alternative source of hematopoietic stem cells
(HSCs) and mesenchymal stem cells (MSCs) is human umbilical
cord blood. Hematopoietic stem cells give rise to all the
types of blood cells: red blood cells, B lymphocytes, T lymphocytes,
natural killer cells, neutrophils, basophils, eosinophils,
monocytes, macrophages, and platelets. Mesenchymal stem cells
give rise to a variety of cell types: bone cells (osteocytes),
cartilage cells (chondrocytes), fat cells (adipocytes) and
other kinds of connective tissue cells such as those in tendons.
Since the population percentage of stem cells is small, the
capture and expansion of stem cells is essential in order
to propagate sufficient cells for research, clinical and
biomedical applications and tissue engineering. We have
shown that functionalized random, aligned and core-shell
nanofiber mats support the adhesion and proliferation of
endothelial and smooth muscle cells for blood vessels, fibroblasts
for dermal substitution, osteoblasts for bone regeneration,
hepatocytes for potential liver regeneration, and neural
stem cells for nerve regeneration. We have been able to expand
CD34+ hematopoietic stem cells on animated PCL nanofiber
mesh for hematological malignancies, and capture human mesenchymal
stem cells using collagen nanofiber scaffolds for bone implantation.
The core-shell nanofibers developed in our laboratory can
be used to encapsulate growth factors and bioactive molecules
to further enhance the biomimetic properties of the scaffolds.
Release kinetic studies of core-shell nanofibers encapsulating
fluorescein isothiocyanate conjugated bovine serum albumin
(FITC-BSA) cultured with/without human dermal fibroblasts
(HDFs) has shown a gradual release of FITC-BSA instead of
a burst release profile. This release profile is crucial
for regulating cell growth if the nanofiber scaffolds for
tissue engineering applications are to encapsulate bioactive
molecules. The proposed
research aims for the expansion of the hematopoietic stem
cells (CD34+) using functionalized nanofibers for the management
of hematological malignancies, breast cancer, thalassemia,
sickle cell diseases and aplastic anemia. Work in our laboratory
on cell adhesion, co-culture and cell proliferation on nanofiber
scaffolds has demonstrated that nanofibers can provide a
conducive environment for stem cell capture and expansion.
The hypothesis is that the modified nanofiber mesh architecture
provides a unique microenvironment to facilitate the expansion
of hematopoietic and mesenchymal stem cells. The research
is also targeted at the capture and expansion of mesenchymal
stem cells, elucidating some of the molecular mechanisms
underlying mesenchymal stem cell differentiation into chondrocytes,
osteocytes, osteoblasts, vascular endothelial cells, smooth
muscle cells, neuronal stem cells, and fibroblasts, and the
key environmental triggers determining these cascades, notably:
growth factors and mechanical stimuli, including shear stress,
disturbed flow, uniaxial and biaxial stretching using functionalized
electrospun nanofibers (aligned, random and core-shell nanofibers)
as a model system. The goal is to understand the sensing
of mechanical cues and the link to modulated gene expression
and eventually cellular function.
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