Aging cancer transformations and dissolution of peaks of

is a biological process that induces changes in   the structural integrity and physiological function
of tissues leading to age- related degenerative diseases and impairment of
various bodily functions over the lifespan of an individual. Stem cells are
reservoir for a variety of autocrine/paracrine factors like cytokines,
chemokines which initiate repair, restoration or regeneration of injured
tissues. In this study, we hypothesized that the stem cell secretome, which is
comprised of a wide array of growth factors secreted by stem cells, may have
beneficial effects on the process of aging/cell senescence. Primary culture of
Dental Pulp Stem Cells (DPSCs) was established from human dental tissue and secretome
was harvested by growing the DPSCs in log phase. Aging in animal model was
induced by daily administration of D-Galactose for 10-12 weeks. Development of aging model was first
confirmed through various functional assays which demonstrated the
deterioration of locomotor activity, reduced muscle strength and degenerative
changes at organ level like liver and kidney. Injection of DPSC secretome
resulted in improvement of kidney and liver functions as observed by various
biochemical tests. Fourier Transform Infrared Spectroscopy (FTIR) of the brain
and liver samples showed the reversal of cancer transformations and dissolution
of peaks of amyloid ? which is associated with Alzheimer’s after secretome
treatment. Functional assays, like Rota Rod and Hole Board showed improvement
of locomotor activity and muscle strength in the animals. Overall, an
improvement in body functions of animals was observed after secretome treatment
which suggested the reversal of age related degenerative changes. Molecular analysis
of telomere shortening and aging array of ~80 genes provided a nice
illustration of genes involved with degeneration and regeneration in aging
after D-Galacose/secretome treatment respectively. Deeper insights into protein
profile of DPSC secretome by nano LC-MS/MS helped us to delineate important
proteins which can be of proven clinical significance for different
degenerative diseases. Our study enumerates an alternate therapeutic strategy
that avoids the direct application of living cells. The results in our study
establish a strong foundation to bypass cell based stem cell therapy and pave a
way to stem “cell free” therapy by using secretome. This pre-clinical study can
help us to design further clinical studies. An exclusive use of DPSC-secreted
molecules rather than the cells can be one way of circumventing the limitations
of stem cell-based therapy without compromising its advantages.


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