The Use of Conditioned Medium in Regenerative Medicine

Updated: May 10

The conditioned medium is secreted by cultured cells and contains various growth factors, metabolites, extracellular matrix proteins, and tissue regenerative agents. Several studies on stem cell-derived secreted factors showed that the secreted factor alone, without the stem cell, could promote tissue repair when applied in different conditions [1].


The secreted factors are referred to as secretome, microvesicles, or exosomes and can be found in the medium where cells are cultured. The conditioned medium has a promising prospect for regenerative medicine due to the abundance of factors that can enhance tissues and organs’ regeneration [1].


Mesenchymal stem cells (MSC) remain a promising platform for regenerative medicine, and their therapeutic potency is mainly associated with their ability to secrete multiple factors critical for tissue regeneration [2]. The secreted conditioned medium contains different cytokines and growth factors that have shown to be very promising for the treatment of various diseases and tissue regeneration. Diomede et al. (2018), for instance, showed that the conditioned medium derived from human gingival-derived MSCs played a key role in the induction of the osteogenic process and in bone regeneration, as it recruits bone progenitor cells and endogenous MSCs and promotes increasing osteogenic gene expression and mineralization [3].


Beyond bone regeneration, the conditioned medium also has the potential to act as a regenerative agent of skin cells, promoting wound repair and tissue regeneration due to its content of regenerative biomolecules that can increase migration and proliferation of fibroblasts in vitro [4].



Figure 1: The mechanisms of the main therapeutic applications of the conditioned medium [5].


Noverina et al. (2019) obtained conditioned medium (CM) from adipose tissue-derived MSCs (CM-hATMSCs) at various passages and evaluated the concentration of different modulators, or growth factors, in early, moderate and late passages. They confirmed that the highest concentration level found in CM-hATMSCs is from Fibroblast Growth Factor (FGF). Therefore, CM-hATMSCs might increase the migration and proliferation of fibroblasts in vitro, and also accelerate the healing process, which makes it an interesting tool for wound healing and regeneration of cells to be used in clinical applications and also on the generation of anti-aging products [4].


A regenerative therapy mediated by biodegradable micro/nano-electrospun fibers loaded with a highly active conditioned medium from adipose-derived stem cells (ADSC-CM) was proposed by Chen et al. (2021) [6]. This therapeutic system was loaded with CM and was built up by protein freeze-drying and emulsion electrospinning technologies. During in vitro essays, the ADSC-CM released by the fibers induced the migration of fibroblasts. Also, ADSC-CM inhibited the transformation of fibroblasts into myofibroblasts and suppressed excessive extracellular matrix production. The use of conditioned medium to treat wounds during in vivo essays significantly accelerated wound closure and improved regeneration outcome, showing superior pro-regenerative performance. These analyses paved a path for applying conditioned medium in the field of regenerative medicine, providing a strong experimental basis for further studies [6].

Figure 2: Conditioned medium (CM) promotes wound healing and inhibits scar formation in vivo [6].




REFERENCES

1. Pawitan, J. A. Prospect of stem cell conditioned medium in regenerative medicine. Biomed Res. Int. 2014, 965849 (2014).

2. Sagaradze, G. et al. Conditioned Medium from Human Mesenchymal Stromal Cells: Towards the Clinical Translation. Int. J. Mol. Sci. 20, (2019).

3. Diomede, F. et al. Biotherapeutic Effect of Gingival Stem Cells Conditioned Medium in Bone Tissue Restoration. Int. J. Mol. Sci. 19, (2018).

4. Noverina, R. et al. Growth factors profile in conditioned medium human adipose tissue-derived mesenchymal stem cells (CM-hATMSCs). Clinical Nutrition Experimental 24, 34–44 (2019).

5. Dai, M., Zhang, Y., Yu, M. & Tian, W. Therapeutic applications of conditioned medium from adipose tissue. Cell Prolif. 49, 561–567 (2016).

6- Chen, L. et al. Conditioned medium-electrospun fiber biomaterials for skin regeneration. Bioact Mater 6, 361–374 (2021)


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