Potential Consequences of the Use of Adipose-Derived Stem Cells in the Treatment of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) ranks as the most prevalent of primary liver cancers and stands as the third leading cause of cancer-related deaths. Early-stage HCC can be effectively managed with available treatment modalities ranging from invasive techniques, such as liver resection and thermoablation, to systemic therapies primarily employing tyrosine kinase inhibitors. Unfortunately, these interventions take a significant toll on the body, either through physical trauma or the adverse effects of pharmacotherapy. Consequently, there is an understandable drive to develop novel HCC therapies. Adipose-derived stem cells (ADSCs) are a promising therapeutic tool. Their facile extraction process, coupled with the distinctive immunomodulatory capabilities of their secretome, make them an intriguing subject for investigation in both oncology and regenerative medicine. The factors they produce are both enzymes affecting the extracellular matrix (specifically, metalloproteinases and their inhibitors) as well as cytokines and growth factors affecting cell proliferation and invasiveness. So far, the interactions observed with various cancer cell types have not led to clear conclusions. The evidence shows both inhibitory and stimulatory effects on tumor growth. Notably, these effects appear to be dependent on the tumor type, prompting speculation regarding their potential inhibitory impact on HCC. This review briefly synthesizes findings from preclinical and clinical studies examining the effects of ADSCs on cancers, with a specific focus on HCC, and emphasizes the need for further research.

Keywords: adipose-derived stem cells; anti-cancer therapy; cell-based therapy; conditioned medium; hepatocellular carcinoma.

Figure 1

Indicators of the potential mechanisms of the pro- and anti-cancer effects of ADSCs, as well as the possible impact of cancer cells on ADSCs, promoting their neoplastic transformation. Unspecified factors secreted by ADSCs cause apoptosis and the inhibition of cancer cell proliferation in co-cultures in vitro. On the other hand, cancer cells can, through an unknown mechanism, cause the malignant transformation of ADSCs, manifested by the expression of a cancerous phenotype.

Figure 2

Potential ways of administrating native and modified ADSCs and ADSC exosomes independently or in combination therapies. The intranasal administration of ADSC-derived exosomes has been proven to be effective in the treatment of ischemic nerve damage in mice [125], but their effectiveness in the treatment of cancer has not yet been confirmed.