AN EFFICIENT EX VIVO EXPANSION OF ADULT MESENCHYMAL STEM CELLS IN SCAFFOLDS - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 834

In addition to their morphological characteristics, MSCs have
the potential for extensive self-renewal, multilineage differen-
tiation, and immunomodulation. 9 , 12 , 13 Under appropriate cul-
ture conditions, MSCs are capable of differentiating into cell
from multiple lineages, such as osteoblasts, adipocytes, chon-
drocytes, and myoblasts. 7 , 13 - 15 A variety of growth factors and
transcription factors are involved in lineage-specific differenti-
ation and transdifferentiation of MSCs. The mechanisms that
underlie lineage-specific differentiation are extensively reviewed
elsewhere. 16
The immunomodulatory effect of MSCs has also been recently
demonstrated. MSCs were shown to modulate the functions of
innate and adaptive immune cells and thus suppress inflamma-
tory responses and modulate their survival. 9 MSCs can also sup-
press the proliferation, differentiation, and cytotoxicity of resting
natural killer (NK) cells. 9 , 17 , 18 Similarly, proliferation, interferon- γ
production, and cytotoxicity of preactivated NK cells is decreased
in the presence of MSCs. 9 , 17 - 22 It is noteworthy that MSCs are only
susceptible to cytokine-activated but not resting NK cells. 18 , 20 , 22
The inhibitory effects of MSCs on the differentiation of mono-
cytesandCD34 + hematopoieticprogenitorsintoimmaturemyeloid
dendritic cells (DCs) have been demonstrated. In addition, MSCs
are able to suppress tumor necrosis factor production by DCs
and increase interleukin-10 (IL-10) production by plasmacytoid
DCs. 23 - 26 MSCs are also able to inhibit in vitro Tcelproif-
eration and function in both naive and memory T cells. 27 - 30
Therefore, MSCs appear to have significant immunosuppressive
potential. 30
Ex vivo expansion is one of the most substantial challenges in
the use of MSCs for clinical applications, particularly with regard
to tissue engineering strategies for large lesions in bone. Therapeu-
tic use of MSCs still depends on isolation and ex vivo expansion of
MSCs because of their low prevalence in adult tissues. 31 Numer-
ous factors can modulate the proliferative capacity of MSCs. They
include donor age, plating density, serum type, and the presence
of various cytokines and growth factors. 31 So far, several growth
factors such as fibroblast growth factor (FGF), epidermal growth
factor (EGF), platelet-derived growth factor (PDGF), transforming