Table 2.

Roles of MSCs in anticancer therapeutic resistance

In vitro or in vivo	Source of MSCs	In vivo model	Cancer types	Functions	Mechanisms	References
In vitro and in vivo	Human BM	NOD/SCID mice with BV173 tumor	CML	Nonselectively protecting CML cells	Protecting CML cells from imatinib-induced cell death via the CXCL12/CXCR4 axis	[87]
In vitro	Murine and human BM	–	CLL	Antagonizing forodesine-induced CLL cell apoptosis	Inhibiting forodesine-induced RNA- and protein-synthesis activity and increasing the expression of Mcl-1	[88]
In vitro	Human BM	–	MM	Enhancing MM cells’ resistance to bortezomib	Secreting CXCL13	[89]
In vitro	Human BM	–	HNC	Increasing chemoresistance to paclitaxel	Secreting several mediators, such as IL-6, IL-7, IL-8, IGF and EGF	[90]
In vitro	TA-MSCs isolated from ascites of ovarian cancer patients and human BM	–	Ovarian cancer	Inducing the resistance of HIPEC	Activating the CXCL12-CXCR4 axis	[91]
In vivo	Human and murine BM	BALB/c mice with C26 tumor, C57BL/6 mice with LLC tumor and nude mice with MDA-231-MB tumor	Colon carcinoma, lung cancer, breast cancer	Protecting tumor cells against chemotherapeutics	Systematically secreting two different PIFAs	[94]
In vitro and in vivo	Human BM	Nude mice with control or methylated MSCs	Soft tissue sarcomas-like	Promoting resistance to cisplatin and contributing to tumor relapse	Transforming into CSCs	[97]
In vitro and in vivo	Human BM	NOD/SCID mice with SUM159 tumor	Breast cancer	Regulating CSCs to accelerate tumor growth	Secreting several cytokines, such as CXCL7 and IL-6	[57]
In vitro and in vivo	Human BM	Nude mice with LoVo tumor	Colorectal cancer	Inducing the formation of CSCs	Tumor cells released IL-1 which induced MSCs to secrete PGE2 and increase the level of IL-6, IL-8 and CXCL1	[93]
In vitro and in vivo	Human BM	SCID mice with PANC1 or A549 tumor	PDAC; lung cancer	Increasing tumor growth and enhancing chemoresistance	Increasing CXCL10 expression	[98]
In vitro and in vivo	Human AD	Nude mice (BALB/c-nu/nu) with MDA-MB-231 tumor	Breast cancer	Inducing chemoresistance of tumor cells	Altering phosphorylation state of several tyrosine kinases, such as WNK1, c-Jun, STAT3 and p53	[99]
In vitro and in vivo	Human UC	Nu/Nu nude mice with MDA-MB-231 tumor	Breast cancer	Suppressing breast cancer pathogenesis and sensitizing cancer cells to radiotherapy	Blocking STAT3 pathway and decreasing CSCs’ stemness	[102]

UC umbilical cord; TA tumor-associated