Tissue Engineering: Focus on the Musculoskeletal System - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 200

Cells
Cells are the building blocks of living tissues and play a key role in tissue
repair processes. Tissue engineering scaffolds can be implanted acellularly
and become infiltrated with local cells upon implantation. However, as the
body grows older and loses its ability to regenerate, stem population is
decreased and injuries can occur more readily. Therefore, transplanting a
vibrant population of cells with a new ability to regenerate can be used to
aid this regenerative process. Stem cells represent a promising cell source
for tissue engineering because of their unique ability to self-renew and dif-
ferentiate down multiple lineages. There are two major classes of stem cells:
adult stem cells and embryonic stem cells. Adult stem cells are multipotent
cells that can be isolated from many adult tissues, such as bone marrow and
adipose tissues. Embryonic stem cells are derived from embryos, that is,
fertilized female eggs, which are normally fertilized in vitro and donated
to research with the consent of the donors. This section focuses on recent
advances in cell-based therapy for musculoskeletal tissue engineering,
with a focus on the use of adipose-derived stem cells (ADSCs), induced
pluripotent stem (IPs) cells, and stem-cell homing.
Adipose-derived Stem Cells
Adipose-derived stem cells (ADSCs) are isolated from fat tissue and have
advantages that include relative abundance and ease of isolation via a min-
imally invasive procedure. ADSCs have the potential to differentiate along
multiple cell lineages into osteoblasts, chondrocytes, endothelials, myo-
cytes, and other cell types. [29]. ADSCs have been shown to secret a broad
spectrum of paracrine factors, including vascular endothelial growth fac-
tor (VEGF), hepatocyte growth factor (HGF), and transforming growth
factor-β (TGF-β). Under hypoxia conditions, ADSCs up-regulate VEGF
production, which makes them particularly attractive candidates for treat-
ing ischemic diseases. Rehman et al. investigated the angiogenic poten-
tial of ADSCs in a murine hind-limb ischemia model [30]. Conditioned
medium from ADSCs under hypoxia promoted endothelial cell prolif-
eration while decreasing the apoptosis. Injection of ADSCs into the tail
vein of mice suffering from hind limb ischemia restored blood perfu-
sion in the ischemic limb to approximately 60% (relative to non-ischemic)
after 10 days, while the non-treated groups showed a base line increase
of only 25%. After direct injection of labeled ADSCs into the tibialis ante-
rior muscle, only 28% of implanted cells were detectable after one week,
suggesting that cell survival after transplantation needs to be improved.
In another study, by Bhang et al., ADSCs were delivered into a hind-limb
ischemia model via a heparin-containing PLGA nanosphere/fibrin car-
rier loaded with fibroblast growth factor-2 (FGF2). The FGF2 was shown