_1698903944 20231102054544000 Rovedar Daryoushbabazadeh@gmail.com Rovedar Journal of Lab Animal Research J Lab Anim. Res 2980-9703 10 25 2023 2 5 Shimen Gevargiz Sangar https://orcid.org/0009-0002-6200-2733 Negar Agahi https://orcid.org/0009-0007-3920-0885 Alireza Azizi https://orcid.org/0009-0005-1184-9127 Nikoo Sadat Hasheminezhad https://orcid.org/0009-0006-0139-2650 Emad Ghannad https://orcid.org/0009-0005-2739-5756 Parmida Nafei https://orcid.org/0009-0003-5495-1565 Mohammad Moeen Babayi https://orcid.org/0009-0002-7790-0210 The remarkable regenerative abilities and versatility of stem cells have long attracted researchers. Recently, in vivo studies have revealed exciting results related to stem cells, particularly their use in cancer treatment. This review will provide an overview of these discoveries and their broader implications for the future. There is growing in vivo evidence that stem cells have immense therapeutic potential in treating various diseases, including cancer, because of their self-renewal and differentiation capabilities. As a result of in vivo research, critical aspects of stem cell behavior within tumor microenvironments have been clarified, providing a deeper understanding of their potential therapeutic utility. Several in vivo studies have demonstrated the potential of stem cell-engineered tumor-targeting agents or therapeutic payloads for the precise delivery of medicinal drugs when these agents are engineered to express them in tumor cells. Through targeted therapies, off-target effects can be minimized, and the therapeutic index of the anti-cancer agents can be improved. Several stem cell-based delivery systems have shown remarkable efficacy in preclinical in vivo studies, including breast, lung, and pancreatic cancer, indicating their potential as a novel therapeutic strategy. Moreover, in vivo studies have revealed that the immunomodulatory properties of stem cells modulate the immune response and modify the tumor microenvironment to suppress it. In particular, using checkpoint inhibitor therapy with stem cells has paved the way for innovative immunotherapeutic strategies. Research on stem cells in vivo has also provided invaluable insights into stem cell biology and their interaction with cancer cells. Due to these findings, there is an increasing understanding of tumor initiation, progression, and resistance mechanisms, which has opened avenues for improving cancer treatment by developing more effective treatments. As a result of the in vivo studies that have taken place so far, there is a wealth of information regarding the potential of stem cells in cancer treatment. 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