WITHDRAWN: Effects and mechanisms of mesenchymal stem/stromal cell functions for treatment of hematologic malignancies: promises and challenges

Abstract

// Myoung Woo Lee 1, 2, * , Somi Ryu 3, * , Dae Seong Kim 1, 2 , Ji Won Lee 1 , Ki Woong Sung 1 , Hong Hoe Koo 1, 2, 4 and Keon Hee Yoo 1, 2, 5 1 Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul, Korea 3 Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea 4 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea 5 Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul, Korea * These authors contributed equally to this work Correspondence to: Keon Hee Yoo, email: hema2170@skku.edu Keywords: mesenchymal stem/stromal cell; hematologic malignancy; leukemia; anti-cancer therapy; cell therapy Received: August 29, 2017 Accepted: November 16, 2017 Published: January 02, 2018 ABSTRACT Mesenchymal stem/stromal cells (MSCs) are known for being multi-potent; however, they also possess anti-cancer properties, prompting efforts to adapt MSCs for therapies. However, MSCs have also been widely implicated in pathways that, on the contrary, contribute to tumor growth. Numerous studies have been conducted to adapt MSCs for further clinical use, but the results have been inconclusive, possibly due to the heterogeneity of MSC populations. Moreover, the conflicting roles of MSCs in tumor inhibition and tumor growth impede their adaptation for anti-cancer therapies. Anti-tumorigenic and pro-tumorigenic properties of MSCs in hematologic malignancies are not as well established as they are for solid malignancies and data comparing them are still limited. In this review, cancer-related influences of MSCs on hematologic malignancies, such as leukemia and lymphoma, are discussed in addition to underlying mechanisms, as well as sources of MSCs and effects on different cancer types. This review describes how MSCs preserve both anti- and pro-tumorigenic effects, as they tend to not only inhibit tumor growth by suppressing tumor cell proliferation, but also promote tumor growth by suppressing tumor cell apoptosis. Thus, clinical studies trying to adapt MSCs for anti-cancer therapies should consider that MSCs could actually promote hematologic cancer progression. It is necessary to take extreme care in developing MSC-based cell therapies in order to boost anti-cancer properties while eliminating tumor-favoring effects. This review emphasizes that research regarding therapies with MSCs must consider the fact that they exert both anti- and pro-tumorigenic effects on hematologic malignancies.