MSC-CM Supporting Effective Cancer Recovery

Cancer is a disease caused by abnormal cell proliferation in the body, leading to genetic mutations and the uncontrolled growth of these cells. There are various types of cancers, and treatment measures depend on the type of cancer, the stage of the disease, and the patient’s overall health. According to the World Health Organization (WHO), cancer is a leading cause of global mortality. Globally, it was projected that there would be 19.3 million new cancer cases and 10 million cancer-related deaths in 2020. Vietnam ranks in the top 10 countries for cancer incidence and mortality annually (WHO). Current cancer treatment methods include surgery to remove tumors or cancer cells by cutting them out with a knife or using heat-based devices to destroy them, chemotherapy using specialized drugs to kill or inhibit the growth of cancer cells, radiation therapy using radiation to kill or inhibit the growth of cancer cells, hormone therapy to control the growth of cancer cells. Combining these treatment methods can enhance overall effectiveness. Additionally, other treatment approaches such as stem cell therapy, immunotherapy, gene therapy, and high-intensity focused ultrasound therapy are also being researched and developed. However, cancer treatment is complex and may have various side effects.

What is the Mesenchymal Stem Cell-Conditioned Medium (MSC-CM)?

Mesenchymal Stem Cells (MSCs) are mature stem cells with significant potential for medical regeneration [1]. In vitro, MSCs release a secretome into the cell culture environment consisting of various factors, such as extracellular vesicles (EV), cytokines, chemokines, and growth factors. The combination of the cell culture medium and this secretome is known as the conditioned environment (MSC-CM) [2]. Recent studies show that non-cellular therapy with MSC-CM has immense potential compared to MSC-based treatments. Through the design of MSCs and extracellular vesicles, we can overcome the limitations of conventional cell therapies and develop conditioned medium and extracellular vesicles as innovative treatment approaches.

Figure 1: Immunomodulatory Effects of MSC. MSC can influence the immune system by either enhancing or inhibiting the proliferation, differentiation, maturation, or activation of lymphocytes and other cells related to both adaptive and innate immune systems [3]

Advancements in the Application of MSC-CM in Cancer Treatment and Recovery

As we know, the use of MSC has increased in regenerative medicine over the past decade [4]. Their immunomodulatory properties restrain numerous unfavorable immune reactions (Figure 1) [3]. Recent studies have explored the natural inclination of MSCs toward diseased tissues, including cancer, through their regenerative potential as a targeted therapy delivery and drug distribution mechanism [1, 5]. Ensuring their safety is crucial to the expanding application of MSCs in regeneration and potential utilization for targeted therapy [6]. Although the exact reasons for the effects of MSCs on cancer are not yet clear, the components secreted by MSCs may be factors influencing cancer cells, and these factors play a decisive role in inhibiting cancer.

Collected in vitro experimental research shows that MSC-CM can be derived from various MSC sources, such as BM-MSC, AD-MSC, UC-MSC, and WJ-MSC. These sources have been proven to exhibit distinct effects on cancer cells originating from different tissues, either inhibiting or enhancing their cancer-promoting properties [7-9]. Additionally, MSC-CM from sources like G-MSC, DP-MSC, L-MSC, A-MSC, O-MSC, FD-MSC, and UTC-MSC inhibit cancer-promoting properties [10-14]. However, limited studies prevent us from confirming whether MSC-CM from G-MSC, DP-MSC, L-MSC, A-MSC, O-MSC, FD-MSC, and UTC-MSC exhibit different effects on cancer cells from various tissue origins. Therefore, tissue origin may not be the sole determining factor for the type of effect MSC-CM exhibits on cancer.

Nevertheless, the mentioned factors may contribute to the observed effects of MSC-CM in various cancers with similar and different tissue origins. Future studies should focus on evaluating the impact of MSCs from a single source on a range of cancer cell lines originating from different tissues or assessing the effects of MSCs from a broad source on cancer cell lines from a single tissue. It is essential to acknowledge that in vitro studies lack immune system components. Future systemic assessments should concentrate on in vivo studies exploring the effects of MSCs on cancer cells to evaluate the immunomodulatory effects on cancer inhibition/progression through MSC intermediaries. Furthermore, a major limitation noted in the studies includes not providing details about dose-dependent side effects. Additionally, most studies did not describe signaling pathways leading to cancer inhibition/progression, and no profiles of MSC-CM were established to identify growth factors, cytokines, and chemokines responsible for anti-cancer/pre-cancer effects. Based on the observed limitations in the studies, the authors propose a standardized protocol for future in vitro studies to evaluate the efficacy of MSC-CM on various cancer cell lines.

Currently, there have been numerous scientific studies demonstrating the potential of MSC-CM in cancer treatment through in vitro and in vivo research. In 2018, He and his colleagues at Peking University demonstrated that MSC-CM can inhibit the growth of tumors and enhance the sensitivity of breast cancer cell radiotherapy in both cell and mouse models [15]. The research indicated that inhibiting STAT3 signals (essential for tumor development) combined with radiotherapy, is a promising direction in the treatment of malignant breast cancer. Specifically, the study showed that MSC-CM treatment of MDA-MB-231 cells, combined with radiation, significantly inhibited cell proliferation and activated Stat3. Stat3 activation regulates tumor invasion by modulating the gene transcription of matrix metalloproteinase 2 (MMP-2), MMP-9, TGF-β1, and β-catenin, all of which decrease after MSC-CM treatment.

These results suggest that the inhibitory effects of MSC-CM combined with radiotherapy on tumor metastasis, may occur through the epithelial-mesenchymal transition pathway. More recently, in 2023, Dr. Bagheri’s study on squamous cell carcinoma (SCC)–a metastatic cancer with limited or recurrent treatment methods [2, 14]. The study demonstrated that the use of MSC-CM reduced the survival and proliferation capabilities of cancer cells, as well as increased the cancer cells’ self-destruction ability.

Prospects of MSC-CM in the Future of Cancer Treatment

While there is still inconclusive evidence regarding the use of MSC-CM therapy in cancer treatment and metastasis prevention, the promising results observed in both in vitro and in vivo experiments are encouraging. Moreover, this non-cellular therapy method ensures the necessary safety during implementation. Additionally, the significant potential lies in MSC-CM derived from sources such as AD-MSC-CM, BM-MSC-CM, and UC-MSC-CM, all of which have shown inhibitory effects on cancerous tissue. Future studies should explore the gene, proteomic, and component configurations of MSC-CM and correlate them with their supportive and anti-cancer effects. Deciphering the molecular pathway of cancer inhibition/progression through MSC intermediaries can help identify factors determining the type of effects caused by specific MSCs on cancer cells. Although this therapy has not undergone extensive clinical trials yet, and many questions remain unanswered, it holds promise for the future.

References:

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