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Volume 02
Stem Cells 2019 & Pediatrics Congress 2019
November 06-07, 2019
Journal of Clinical Genetics and Genomics
November 06-07, 2019 | Tokyo, Japan
STEM CELLS AND REGENERATIVE MEDICINE
PEDIATRICS AND CHILD CARE
International Conference on
2
nd
World Congress on
&
J Clin Gen Genomics, Volume 02
Immunity boost and increased lifespan of tumor necrosis factor-α/CD40 ligand-
engineered mesenchymal stem cells administred in mice
Farid Menaa
California Innovations Corporation, USA
T
he interaction between mesenchymal stem cells (MSCs) and dendritic cells (DCs) affects T cell development and function.
Further, the chemotactic capacity of MSCs, their interaction with the tumor microenvironment and the intervention of
immune-stimulatory molecules suggest possible exploitation of tumor necrosis factor-α (TNF-α) and CD40 ligand (CD40L)
to genetically modify MSCs for enhanced cancer therapy. Both DCs and MSCs were isolated from BALB/c mice. DCs were
then cocultured with MSCs transduced with TNF-α and/or CD40L [(TNF-α/CD40L)-MSCs]. Major DCs' maturation markers,
DC and T cell cytokines such as interleukin-4, -6, -10, -12, TNF-α, tumor growth factor-β, as well as T cell proliferation, were
assessed. Meantime, a BALB/c mouse breast tumor model was inducted by injecting 4T1 cells subcutaneously. Mice (n =
10) in each well-defined test groups (n = 13) were cotreated with DCs and/or (TNF-α/CD40L)-MSCs. The controls included
untreated, empty vector-MSC, DC-lipopolysaccharide and immature DC mouse groups. Eventually, cytokine levels from murine
splenocytes, as well as tumor volume and survival of mice, were assessed. Compared with the corresponding controls, both
in
vitro
and
in vivo
analyses showed induction of T helper 1 (Th1) as well as suppression of Th2 and Treg responses in test groups,
which led to a valuable antitumor immune response. Further, the longest mouse survival was observed in mouse groups that were
administered with DCs plus (TNF-α/CD40L)-MSCs. In our experimental setting, the present pioneered study demonstrates that
concomitant genetic modification of MSCs with TNF-α and CD40L optimized the antitumor immunity response in the presence
of DCs, meantime increasing the mouse lifespan.
dr.fmenaa@gmail.com