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Table 5 MSC suppression effects in cancers

From: Mesenchymal stem/stromal cell-based therapy: mechanism, systemic safety and biodistribution for precision clinical applications

Cancer type/MSC source

Surface marker

Effect

Factors/mechanisms

Ref.

Brain cancer

 Human bone marrow from femoral head of individuals undergoing hip-replacement surgery

CD44+ CD90+ CD105+

Decreased tumor growth and angiogenesis

Coculture with hBMMSCs decreased PDGF-BB and IL1β secretion

[184]

 Human bone marrow from Lonza

CD29+ CD44+ CD105+ CD166+ CD90+ CD73+

CD14− CD34− CD45−HLA-DR− CD19−

Decreased tumor cell proliferation

MSC-EV

[281]

 Human bone marrow of healthy donor

Not stated

Inducing apoptosis in CD133-positive primary glioma cells

Engineered TRAIL-expressing MSCs induced apoptosis of glioma cells

[198]

 Human bone marrow of healthy donor

CD44+ CD105+ CD34− CD38− CD45−

Decreased cancer cell proliferation and increased animal survival

Engineered IFNβ-expressing MSCs

[201]

 Human subcutaneous adipose tissue of 18–30 years old mothers receiving cesarean sections

CD13+ CD44+ CD90+ CD105+ CD14− CD34− CD45−

Decreased cancer cell proliferation

Increased apoptosis; G0/G1 cell cycle arrest

Upregulation of caspase-3 and caspase-9 and downregulation of survivin and XIAP

[170]

 Human adipose tissue from liposuction

CD29+ CD44+ CD90+ CD105+

Decreased tumor growth and formation

Paracrine effects by MSC-secreted cytokines

[289]

 Human adipose tissue from patients receiving liposuctions (commercial)

CD29+ CD44+ CD73+ CD90+ CD105+ CD166+ CD14− CD31− CD45− Lin1−

Decreased tumor growth, migration; induced differentiation; no significant effect in survival

Engineered BMP4-secreting MSCs had additional effect of improved survival

[204]

 Human umbilical cords of 18–30 years old mothers receiving cesarean section

CD13+ CD44+ CD90+ CD105+ CD14− CD34− CD45−

Decreased cancer cell proliferation

Increased apoptosis; G0/G1 cell cycle arrest

Upregulation of caspase-3 and caspase-9 and downregulation of survivin and XIAP

[170]

 Human umbilical cord of healthy donor

CD73 CD105 CD90 CD45 CD34 CD14 CD11b HLA-DR

Decreased cancer stem cell proliferation

Direct cell interaction

[290]

 Human umbilical cord from the cell library of the Chinese Academy of Science

CD29+ CD105+ CD34− CD45−

Decreased tumor growth

Engineered IL-24-secreting MSCs induced tumor cell apoptosis

[200]

 Human umbilical cord Wharton's jelly of healthy donor

CD13+ CD29+ CD44+ CD73+ CD90+ CD105+ CD14− CD34− CD45− HLA-DR−

Decreased cancer stem-like cells proliferation

MSC-CM mediated cell cycle arrest and senescence of cancer cells by downregulating cyclin D1 and upregulating expression of p21 and p16

[171]

 Human umbilical cord Wharton's jelly from CryoSave

Not stated

Decreased tumor cell proliferation

MSC-EV

[281]

 Human umbilical cord blood of healthy donor

CD29+ CD81+

Decreased tumor growth and migration capacity

Co-culture with MSCs increased PTEN expression and downregulated PI3K/AKT pathway in cancer cells

[187]

 Human umbilical cord blood of healthy donor

CD29+ CD81+

Decreased tumor growth and angiogenesis

Co-culture with MSCs downregulated FAK, VEGF, AKT

[185]

 Human umbilical cord blood of healthy donor

CD29+ CD81+

Decreased invasion capacity

Increased cancer cell Mad1 expression represses c-Myc activity and further decreases activity of ERK

[188]

 Human umbilical cord blood of healthy donor

CD29+ CD81+

Decreased migration and invasion capacity

Decreased EGFR and c-Met expression, activity, and physical association

[188]

 Human umbilical cord blood of healthy donors

CD29+ CD81+

Decreased tumor growth

G0/G1 cell cycle arrest; decreased cyclin D1/Cdk4 and cyclin D1/Cdk6 expression

[172]

 Human umbilical cord blood of healthy donors

CD29+ CD81+

Decreased tumor growth and increased apoptosis

Decreased XIAP expression resulted in activation of caspase-3 and caspase-9, downregulated AKT pathway and activated Smac/DIABLO

[173]

 Human umbilical cord blood of healthy donors

CD31− CD45−

Decreased tumor growth and increased tumor cell apoptosis

TRAIL signaling

[148]

 Human umbilical cord blood of healthy donors

CD29+ CD44+ HLA-ABC+ CD34− CD45− HLA-DR−

Decreased tumor growth and angiogenesis

Reduced the number of cyclin D1-positive cancer cells

[174]

 Human umbilical cord blood of healthy donors

Not stated

Decreased tumor growth and angiogenesis; increased the survival of glioma-bearing mice and tumor-specific long-term T-cell immunity

Engineered IL-12 M-secreting MSCs

[199]

 Human umbilical cord blood of healthy donors

Not stated

Enhanced tropism of MSCs towards tumor site

Engineered CXCR4- overexpressing MSCs

[196]

 Human umbilical cord blood from Medipost Co

Not stated

Increased tumor cell apoptosis

Engineered TRAIL-expressing MSCs induced apoptosis of glioma cells

[197]

 Human umbilical cord blood of healthy donors

Not stated

Enhanced tropism of MSCs towards tumor site

Engineered CXCR1- overexpressing MSCs

[196]

Lung cancer

 Human bone marrow of healthy donor

CD29+ CD73+ CD90+ CD105+ CD166+ CD14− CD31− CD34− CD45−

Decreased tumor tumorigenicity and EMT

MSCs-secreted OSM activates OSM/STAT1 signaling pathway

[191]

 Human subcutaneous adipose tissue of 18–30 years old mothers receiving cesarean sections

CD13+ CD44+ CD90+ CD105+ CD14− CD34− CD45−

Decreased cancer cell proliferation

Increased apoptosis; G0/G1 cell cycle arrest

Upregulation of caspase-3 and caspase-9 and downregulation of survivin and XIAP

[170]

 Human umbilical cord of healthy donor

CD29+ CD44+ CD73+ CD90+ CD105+ CD14− CD34− CD45− HLA-DR−

Decreased cancer cell proliferation and migration capacity

Cell cycle arrest; induced apoptosis; downregulated Bcl-2, pro-caspase-7, β-catenin and c-Myc

[175]

 Human umbilical cords of 18–30 years old mothers receiving cesarean section

CD13+ CD44+ CD90+ CD105+ CD14− CD34− CD45−

Decreased cancer cell proliferation

Increased apoptosis; G0/G1 cell cycle arrest

Upregulation of caspase-3 and caspase-9 and downregulation of survivin and XIAP

[170]

 Human umbilical cord Wharton's jelly

CD105+ CD90+ CD166+ CD73+ CD45− CD31− CD34−

Decreased SCC-LCSC tumor cell proliferation and expression of CSC markers

MSC-CM and in vivo co-transplantation

[161]

 Human umbilical cord Wharton's jelly

CD105+ CD90+ CD73+ CD45− CD34−

No effect on AC-A549

Secretome has no effect on AC-A549

[291]

 Human umbilical cord Wharton's jelly

Not stated

Decreased tumor cell growth and increased apoptosis

Engineered IFNβ-expressing MSCs

[202]

 Human endometrium of women with uterine fibroids

CD13+ CD29+ CD44+ CD49+ CD49b+ CD73+ CD90+ HLA-ABC+ CD9− CD14− CD31− CD34− CD40− CD45− CD54− CD117− CD133− HLA-DR−

Decreased migration capacity

Not explored

[191]

Liver cancer

 Human fetal bone marrow at 4 months of gestation from abortion (BMMS-03)

CD105+ CD166+ CD34−

Decreased cancer cell proliferation

Decreased NF-κB expression and activity

[192]

 Human bone marrow of healthy donor

CD44 + CD90 + CD34- CD45-

Decreased tumor growth

Engineered IFNβ-expressing MSCs induced cell cycle arrest and increasing expression of p21, p27 and FOXO3a as well as decreasing protein levels of cyclin D1, pRb and AKT

[203]

 Human fetal dermal tissues at 4 months gestation from abortion (Z3)

CD105+ CD166+ CD34−

Decreased cancer cell proliferation

Decreased NF-κB expression and activity

[192]

 Human fetal dermal tissues at 4 months gestation from abortion (Z3)

CD29+ CD44+ CD105+ CD166+ CD31− CD34− CD45− HLA-DR− vWF−

Decreased tumor growth

Induced apoptosis and cell cycle arrest; Bcl-2, c-Myc, PCNA and survivin were downregulated

[176]

 Human umbilical cord of healthy donor

CD29+ CD44+ CD73+ CD90+ CD105+ CD14− CD34− CD45− HLA-DR−

Decreased cancer cell proliferation and migration capacity

Cell cycle arrest; induced apoptosis; downregulated Bcl-2, pro-caspase-7, β-catenin and c-Myc

[175]

 Human umbilical cord Wharton's jelly

Not stated

Decreased tumor growth

Engineered AFP promoter driving-sTRAIL- expressing MSCs

[208]

Bile duct cancer

 Human umbilical cord of healthy donors

CD29+ CD44+ CD105+ CD34− CD45−

Decreased tumor growth and cell proliferation

MSC-CM inhibits Wnt/β-catenin signaling pathway by GSK-3β

[190]

Pancreatic cancer

 Human umbilical cord blood of healthy donors

CD44+ CD29+ HLA-I+ CD34− CD38− HLA-DR−

Decreased tumor growth and prolonged survival of tumor-bearing mice

Engineered IL-15- expressing MSCs mediate NK and CD8-positive T cells accumulation in tumor site

[211]

Colorectal cancer

 

Human subcutaneous adipose tissue of 18–30 years old mothers receiving cesarean sections

CD13+ CD44+ CD90+ CD105+ CD14− CD34− CD45-

Decreased cancer cell proliferation

Increased apoptosis; G0/G1 cell cycle arrest

Upregulation of caspase-3 and caspase-9 and downregulation of survivin and XIAP

[170]

Human adipose tissue from liposuction

CD29 + CD44 + CD90 + CD105 + 

Decreased tumor growth

Engineered CD-expressing MSCs sensitized colon cancer cells to 5-FC

[212]

Human umbilical cords of 18–30 years old mothers receiving cesarean section

CD13+ CD44+ CD90+ CD105+ CD14− CD34− CD45−

Decreased cancer cell proliferation

Increased apoptosis; G0/G1 cell cycle arrest

Upregulation of caspase-3 and caspase-9 and downregulation of survivin and XIAP

[170]

Ovarian cancer

Human bone marrow

CD105+ CD90+ CD44+ CD73+ CD45− CD34− CD24− HLA-DR− CD14−

Increased tumor cell apoptosis

MSCs-CM induced reduction in the level of CA-125, LDH and beta-hCG and expression of MMP-2, MMP-9, and CA-125 as well as increased TIMP 1, 2, and 3 mRNA expression

[177]

Human adipose tissue from liposuction

CD105+ CD90+ CD44+ CD73+ CD45− CD34− CD24− HLA-DR− CD14−

Increased tumor cell apoptosis

MSCs-CM induced reduction in the level of CA-125, LDH and beta-hCG and expression of MMP-2, MMP-9, and CA-125 as well as increased TIMP 1, 2, and 3 mRNA expression

[177]

Human umbilical cord Wharton's jelly of healthy donor

Not stated

Decreased tumor cell growth and migration

hWJSC-CL and hWJSC-CM induced apoptosis

Upregulation of pro-apoptotic BAX and downregulation of anti-apoptotic BCL2 and SURVIVIN genes

[167]

Human umbilical cord Wharton's jelly

CD73+ CD90+ CD105+

CD34− CD45− CD14− CD20−

Decreased tumor cells proliferation

MSC-CM and MSC-CL decreased the expression of oncogenic cytokines, chemokines and growth factors in cancer cells

[292]

Human umbilical cord Wharton's jelly

CD44+ CD90+ CD105+ CD73+ CD29+ CD34− CD45−

Decreased tumor cells expression of CSC markers; increased cell cycle arrest and apoptosis

MSC-CM and MSC-CL 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) in cancer cells

[178]

Human umbilical cord Wharton's jelly

Not stated

Decreased tumor cells proliferation

Not explored

[293]

Human umbilical cord Wharton's jelly

CD105+ CD90+ CD44+ CD73+ CD45− CD34− CD24− HLA-DR− CD14−

Increased tumor cell apoptosis

MSCs-CM induced reduction in the level of CA-125, LDH and beta-hCG and MMP-2, MMP-9, and CA-125 mRNA expression as well as increased TIMP 1, 2,

and 3 mRNA expression

[177]

Human umbilical cord blood of healthy donors

 

Decreased tumor growth and prolonged survival of tumor-bearing mice

Engineered IL-21-secreting MSCs

[210]

Human endometrium of healthy women

CD73+ CD90+ CD34−

Decreased tumor growth and pro-angiogenetic ability

Inhibition of AKT phosphorylation and decreasing the expressions of VEGFA and HIF-1α in cancer cells, probably by activation of FoxO3a in cancer cells

[186]

Breast cancer

 Resident MSCs of vascular wall

Not stated

Decreased the risk of lung metastasis after radiation-induced injury

Downregulation of radiation-induced expression of endothelial MMP2 and of the SASP factors CCL2 and Plau/uPA

[193]

 Human adipose tissue from normal (non-diabetic) adult lipoaspiration

CD13+ CD29+ CD44+ CD73+ CD90+ CD105+ CD166+ CD14− CD31−CD45−

Decreased tumor cell viability and migration

MSC-secreted conditioned medium inhibits canonical Wnt signalling

[189]

 Human adipose tissue of individuals receiving mammoplasty

Not stated

Decreased tumor cell growth and lung metastasis

Not explored

[294]

 Human umbilical cord of healthy donors

CD73+ CD90+ CD105+ CD45− CD14−

Increased tumor cells apoptosis

MSCs secretome

[295]

 Human umbilical cord Wharton's jelly of healthy donor

Not stated

Decreased tumor cell growth and migration

hWJSC-CL and hWJSC-CM induced apoptosis

Upregulation of pro-apoptotic BAX and downregulation of anti-apoptotic BCL2 and SURVIVIN genes

[167]

 Human umbilical cord Wharton's jelly of healthy donor

CD73+ CD90+ CD105+ CD44+ CD45− CD14− CD34−

Increased tumor cells apoptosis

Upregulating p21

Downregulating PCNA, cyclin D1, Bcl-2, Bcl-xL, and MMPs and upregulating p53 and p21

[168]

 Human umbilical cord Wharton's jelly of healthy donor

CD44+ CD90+ CD105+ CD34−

Decreased tumor cell growth

Intra-tumoral injections of MSC-CM and MSC

[179]

 Mouse umbilical cord Wharton's jelly

Not stated

Decreased tumor cell growth

Increased activated caspase-3

[169]

 Human umbilical cord blood of healthy donors

Not stated

Decreased tumor cell proliferation

MSC-ECM

[296]

 Human umbilical cord blood of healthy donors

Not stated

Decreased tumor cell growth and lung metastasis

Not explored

[294]

Melanoma

 

Human bone marrow of healthy donor

Not stated

Decreased the risk of lung metastasis after radiation-induced injury

Downregulation of radiation-induced expression of endothelial MMP2 and of the SASP factors CCL2 and Plau/uPA

[193]

Resident MSCs of vascular wall

Not stated

Decreased the risk of lung metastasis after radiation-induced injury

Downregulation of radiation-induced expression of endothelial MMP2 and of the SASP factors CCL2 and Plau/uPA

[193]

Bone cancer

 Human umbilical cord Wharton's jelly of healthy donor

Not stated

Decreased tumor cell growth and migration

MSC-CL and MSC-CM induced apoptosis and autophagy; upregulation of pro-apoptotic BAX and autophagy genes (ATG5, ATG7, and BECLIN1); downregulation of anti-apoptotic BCL2, SURVIVIN genes

[167]

 Human umbilical cord Wharton's jelly of healthy donor

CD44+ CD90+ CD105+ CD34−

Decreased tumor cell growth

MSC-CL and MSC-CM induced apoptosis and autophagy

[179]

 Gastric cancer

 Human umbilical cord blood

CD44+ CD105+ CD29+ CD90+

CD38− CD117− CD45− CD34−

Increased tumor cell apoptosis

Engineered TNFSF14-secreting MSCs promote tumor cell apoptosis with elevated caspase-3 expression

[209]

Esophageal cancer

Human umbilical cord Wharton's jelly of healthy donor

CD73+ CD90+ CD105+ CD44+ CD45− CD14− CD34−

Increased tumor cells apoptosis

Upregulate p21 downregulate PCNA, cyclin D1, Bcl-2, Bcl-xL, and MMPs and upregulate p53 and p21

[168]

Bladder cancer

 

 Human umbilical cord Wharton's jelly of healthy donor

Not stated

Decreased tumor growth

MSC-MVs induced down-regulated phosphorylation of Akt protein kinase and up-regulated cleaved Caspase 3

[180]

Hematological cancer

 Human adipose tissue from 3liposuction

CD73+ CD90+ CD105+ CD45−

Decreased tumor cell clonogenicity and

growth

Not explored

[297]

 Human umbilical cord of healthy donor

CD13+ CD29+ CD44+ CD73+ CD90+ CD105+ CD166+ HLA-ABC+

CD14− CD31− CD34− CD38− CD45− HLA-DR−

Inducing granulocytic differentiation

of APL cells

MSCs secreted IL-6 activates MEK/ERK pathways

[194]

 Human umbilical cord of healthy donor

CD73+ CD90+ CD105+ CD45−

Decreased tumor cell clonogenicity and

growth

Not explored

[297]

 Human umbilical cord of healthy donor

CD73 CD90 CD105 CD14 CD19 CD34 CD45 and HLA-DR

Decreased tumor growth

Engineered Tandab -expressing MSCs combined with IDO pathway inhibitor inhibit expression of CD98 and Jumonji

[205]

 Human umbilical cord of healthy donor

Not stated

Decreased tumor cell proliferation

Engineered IDO -secreting MSCs abolish the anti-apoptotic effect of MSCs

[206]

 Human umbilical cord Wharton's jelly of healthy donor

Not stated

Decreased tumor growth and increased tumor cell apoptosis

Engineered scFvCD20-sTRAIL fusion protein -secreting MSCs

[207]

 Human umbilical cord Wharton's jelly of healthy donor

CD105+ CD73+ CD90+ CD45− CD34− CD14− CD11b− CD79α−/ CD19−

Decreased tumor cells viability; increased tumor cells apoptosis

MSC-CM induced CD47 and PD-L1 expression decreased in the tumor cells

[181]

 Human umbilical cord Wharton's jelly of healthy donor

Not stated

Decreased cell viability and mitochondrial membrane potential; increased apoptosis

MSC-CM-3 kDa MWCO regulates cellular H2O2 levels

[182]

 Human umbilical cord Wharton's jelly of healthy donor

CD105+ CD73+ CD90+ CD34− CD45−

Decreased tumor cell proliferation

IFNγ stimulated MSC secretome

[298]

 Human umbilical cord blood of healthy donor

Not stated

Decreased tumor cell proliferation

Direct cell-to-cell contact caused arrest of the growth of cancer cells in the G0/G1 phase

[183]