**9. Conclusion**

In wound defects, ADSCs presented a great ability in migration and were recruited rapidly into wounded sites where the process of cell differentiation toward various skin cell components occurred. However, ADSCs participate more likely in all the phases of wound healing through autocrine and paracrine pathways [6]. Otherwise, during aging, senescent cells increase and the paracrine senescent secretome of ADSCs can trigger and reinforce senescence within their microenvironment [124]. This paracrine effect can be transmitted by ligands of TGF-β by mediating changes in the transcriptional program through SMAD family members [146].

Another surprising capacity of these cells is that secretome derived from younger cells is more suitable to increase proliferation than that derived from older cell [18], suggesting that younger cells have the potential to secrete a youth growth factor identified as GDF11, able to quantitatively increase cell proliferation at the younger stage. Targeted cells are the other crucial parameters leading to this increase; younger cells presented less senescence characteristics including DNA damage and ROS accumulation, thus, inducing cell rejuvenation. This process might be used to directly induce secretome of these cells toward tissue regeneration or rejuvenation.

We cannot exclude that MSCs and ADSCs secreted other cytokines than GDF11 and TGF-β, such as PDGF, IL-1, bone morphogenic protein (BMP)6, BMP9, and exerted autocrine and paracrine effects on DF and keratinocytes, promoting cell differentiation, proliferation, and migration. Nevertheless, the antiaging paracrine effect seemed to be induced, perhaps not exclusively but at least to

**55**

*Adipose-Derived Stem Cells (ADSCs) and Growth Differentiation Factor 11 (GDF11)…*

a significant degree, by a combinatorial effect of both GDF11 and TGF-β. It is probable that both signals vary with age and that the strength of each of them is reciprocal to the sites of secreted signals and to the length of the exposure to the signal. Based on these considerations, further investigations on TGF-β and GDF11 molecular mechanisms' implication on skin rejuvenation are needed to increase our knowledge and draw conclusions on the regulation of aging process. Exciting therapeutic approaches might arise from the implication of GDF11 as an antiaging mechanism to increase the lifespan and the long-lasting functionality of different

The authors wish to thank the University of Mohammed VI Polytechnic for

*DOI: http://dx.doi.org/10.5772/intechopen.91233*

organs.

**Acknowledgements**

funding this work.

**Conflict of interest**

**List of abbreviations**

The authors declare no conflict of interest.

ADSCs adipose-derived stem cells GDF11 growth differentiation factor TGF-β transforming growth factor

VEGF vascular endothelial growth factor PDGF platelets derived growth factor

MCP-1 monocyte chemoattractant protein-1

ECM extracellular matrix DF dermal fibroblasts ROS reactive oxygen species MSCs mesenchymal stem cells MMP1, 2, 9 matrix metalloproteinase1, 2, 9 IL-1, −6, −8, −10 interleukin-1, −6, −8, −10 TNF-α tumor necrosis factor-α

α-SMA α-smooth muscle actin

*Adipose-Derived Stem Cells (ADSCs) and Growth Differentiation Factor 11 (GDF11)… DOI: http://dx.doi.org/10.5772/intechopen.91233*

a significant degree, by a combinatorial effect of both GDF11 and TGF-β. It is probable that both signals vary with age and that the strength of each of them is reciprocal to the sites of secreted signals and to the length of the exposure to the signal. Based on these considerations, further investigations on TGF-β and GDF11 molecular mechanisms' implication on skin rejuvenation are needed to increase our knowledge and draw conclusions on the regulation of aging process. Exciting therapeutic approaches might arise from the implication of GDF11 as an antiaging mechanism to increase the lifespan and the long-lasting functionality of different organs.
