2.2 Mesenchymal stem cells (MSCs)
MSCs, also known as mesenchymal stromal cells, are multipotent stem
cells that can differentiate into numerous cells types such as
osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes
(muscle cells), and adipocytes (fat cells)(Ong, Ankrum, Dastidar, Levy,
& Karp, 2014; Tonk, Witzler, Schulze, & Tobia Sc H, 2020). The
morphology of MSCs is also characteristic, as MSCs have a small cell
body with long and thin processes that are widely dispersed and
populated in the adjacent extracellular matrix. In label-free live cell
imaging, some organelles can be seen, and MSCs are clearly defined due
to these distinct morphological features(Richmond, 1992). According to
the International Society for Cellular Therapy (ISCT), MSCs are
characterized by the following criteria: (1) expression of a specific
set of clusters of differentiation CD markers (CD73, CD90, and CD105),
(2) lack of expression of hematopoietic lineage CD markers [CD45,
CD34, CD14 or CD11b, CD79a or CD19, human leukocyte antigen-antigen D
related (HLA-DR)], (3) plastic adherence under standard culture
conditions, (4) the ability to differentiate into osteoblasts,
adipocytes, and chondroblasts in vitro (Fukumitsu & Suzuki,
2019).
Due to the clear definition, it is much easier to classify MSCs than
EPCs. The most acknowledged classification is cell source, and the most
common extraction sources are umbilical cord blood, amniotic fluid,
adipose, and bone marrow, and different sources of MSCs possess
different biological properties (Figure 2). The abundance and healing
capacity of stem cells from umbilical cord blood are much higher as
compared to amniotic fluid, and adipose and bone marrow stem cells.
However, the replication and differentiation capacity not only correlate
with the cell source, but also with the age of donors. Research shows
that the doubling time and activity generation significantly decrease
when age increases(Fraser, Wulur, Alfonso, & Hedrick, 2006; Pittenger
et al., 1999).
The immunogenicity is also different between different cell sources.
MSCs from bone marrow possess the highest immunogenicity because they
have a higher expression level of HLA-DR under an inflammatory
microenvironment (such as a high concentration of tumor necrosis
factor-α (TNF-α) and interferon gamma (IFN-γ)), which will cause the
immune cells to identify them and more rapidly eliminate them. The
differentiation tendency is also different, as MSCs from umbilical cord
blood tend to secrete additional hematopoietic factors such as G-CSF,
GM-CSF, and HGF. Therefore, this type of MSC is more well-equipped to
support the blood system. Additionally, MSCs from bone marrow can
secrete a greater amount of VEGF than MSCs from umbilical cord blood,
which enables MSCs from bone marrow to more easily form
neovessels(Baksh, Yao, & Tuan, 2007; Hass, Kasper, Böhm, & Jacobs,
2011; Peng et al., 2008; Y.-Y. Shi, R. P. Nacamuli, A. Salim, & M. T.
Longaker, 2005; Van Harmelen, Röhrig, & Hauner, 2004; Weiss et al.,
2006).