Table 2.

Anti-tumor effects of MSCs on the biology of different types of tumors

MSC source	Product administrated	Tumor type	Type of study	Outcome effect	References
Bone marrow	Cells	HepG2 and Huh7 hepatocarcinoma cell	In vitro In vivo	Inhibition of cancer cell proliferation/inhibition of AKT/FOCO3a pathway	[18]
		Primary human glioma cells, HUVEC endothelial cells	In vitro	Reduction in tumor volume and vascular density/reduced expression of platelet-derived growth factor (PDGF)-BB and interleukin (IL)-1β	[19]
		Colorectal cancer cells	In vivo	Administration of MSCs increase the life span of carcinogen-exposed rats by attenuating both colorectal cancer initiation and progression, mediated polarization of resident immune cells which in turn interferes with tumor growth. After fractionated irradiation, MSCs inhibited residual tumor growth, protected healthy tissue and prolonged animal survival	[9]
	Conditioned medium	MDA-MB-231 breast cancer cells	In vivo	Suppressed tumor growth and lung metastasis. Reduced proliferative activity of cancer cells	[20]
		Non-small-cell lung carcinoma cells	In vitro	Inhibition of cell proliferation, viability and migration. Downregulation of mitogen-activated protein kinase (MAPK) signaling pathway	[21]
	Extracellular vesicles	Liver Carcinoma Kaposi’s sarcoma Ovarian tumour cell lines	In vitro	Inhibit proliferation and promote apoptosis	[22]
Adipose tissue	Exosomes	A2780 and SKOV-3 ovarian cancer cells	In vitro	Inhibed proliferation of ovarian cancer cells. Upregulates proapoptotic molecules, induced apoptosis signalling by upregulating different pro-apoptotic signalling molecules (BAX, CASP9, and CASP3), as well as downregulating the anti-apoptotic protein BCL2. Sequencing of exosomal RNAs revealed a rich population of microRNAs (miRNAs), which exhibit anti-cancer activities by targeting different molecules associated with cancer survival, blocking the cell cycle, and activating mitochondria-mediated apoptosis signalling	[23]
Adipose tissue	Cells	U87MG or GSC1 cells Glioblastoma cells	In vitro In vivo	AD-hMSCs showed remarkable tropism towards the tumor, reduction in tumor growth, tumor cell proliferation, and microvascular density	[24]
	Conditioned medium	PC3M-luc2 prostate cancer cells	In vitro In vivo	Inhibit proliferation and promote apoptosis. Reduced the expression of caspase 3/7 with increased antiapoptotic protein, BclxL; effects at least mediated by miR-145 form exosomes released from ASC	[25]
	Extracellular vesicles	Prostate cancer Ovarian cancer Glioblastoma	In vivo In vitro In vivo	Inhibit proliferation and promote apoptosis	[23–25]
Endometrial tissue	Cells	Ovarian cancer cell lines (SKOV3 cells and HO-8910 cells)	In vitro In vivo	Attenuate tumor growth. Induce cell cycle arrest, promote apoptosis, disturb mitochondrial membrane potential and decreasing pro-angiogenic ability	[26]
Uterine cervical tissue	Conditioned medium	MCF-7 and MDA-MB-231 breast cancer cells	In vitro In vivo	Induce cell cycle arrest, promote apoptosis, inhibited proliferation of cancer associated fibroblasts, inhibited macrophage activation, inhibit tumor cell invasion	[27]
Amniotic fluid	Cells	SKOV3 ovarian cancer cells	In vitro	Cytotoxic effect on SKOV3 and suppressed their proliferation; induction of internal and external pathways of apoptosis. Release soluble factors which cause an efficient anticancer effect; induction of its anticancer effects by stimulating the caspase cascade (caspase 3 and 8) and apoptosis. Activation of genes responsible for apoptosis (P53 and P21)	[28]
Placental chorionic villi	Cells	MDA-MB-231 breast cancer cells	In vitro	Reduce the proliferative and migratory capacity of tumor cells, inhibited the endothelial cell-associated vasculogenic capacity	[29]
Umbilical cord	Cells	Line MDA-MB-231 human breast cancer cells	In vivo	Antitumor effect. Inhibited tumor angiogenesis and induced cell apoptosis	[30]
		Liver cancer cell lines HepG2 and SK-Hep-1	In vitro In vivo	Reducing hepatoma cell growth and metastasis. Downregulation of Wnt/β-catenin signaling pathway	[31]
		High-grade human glioma cell lines (SNB19 and U251) and xenograft cell lines (4910 and 5310)	In vitro In vivo	Inhibited tumor growth. Upregulation of PTEN gene phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in tumors induced cellular death through decreasing XIAP expression	[32]
	Conditioned medium	MCF-7 tumor cells	In vitro	Cytotoxic effects on MCF-7 cells by induction of apoptosis	[33]
		Ovarian cancer cell lines (OVCAR3 and SKOV3)	In vitro	Reduction in size of tumor spheres. Increase in the sub-G1 and G2M phases of cell cycle, inhibition of cell migration, activated caspase; decreased expression of cell cycle regulatory genes (cyclin A2, Cyclin E1), prostaglandin receptor signaling genes (EP2, EP4) and the pro-inflammatory genes (IL-6, TNF-α); cycle arrest, apoptosis	[34]
		MG-63 and SKES-1 osteosarcoma cell lines	In vitro In vivo	Decreased tumor sizes/Inhibition of mammary carcinoma and osteosarcoma cells via apoptosis and autophagy	[35]
		HeLa cells	In vitro	Reduced cell viability and increased apoptosis. Increased caspase-3/7 activity, decreased mitochondrial membrane potential, and induced cell cycle arrest	[36]
		MDA-MB-231 breast cancer cells	In vitro In vivo	Suppresses breast cancer cells growth and sensitizes cancer cells to radiotherapy. Inhibition of the Stat3 signaling pathway	[37]