Table 3 Possible causes of discrepancies in the antitumorigenic effects of MSC populations

MSC isolation source

BM (human fetal or adult, mouse) AT (human), UC (human, rat)

Human UC

MSC in vitro/ex vivo expansion

MSC passage, MSC confluence, high serum or growth factor supplemented media, possible contamination with tumor cells

Determine maximum passage No. for MSC/check senescence status, minimize serum of animal origin

In vivo tumor model

Over 60 cell lines representing 15 tumor types (including sarcoma, hepatoma, adenocarcinoma, melanoma, glioblastoma, lymphoma)

At least two different tumor cell lines per cancer

SCID, athymic nu/nu mice

Athymic nu/nu mice (or nude variants)

MSC species origin

Syngeneic, xenogeneic

Human xenograft

MSC : Cancer cell ratio

BM-MSC: 2:1–1:1–1:12

AT-MSC: 1:1–1:10

UC-MSC: 6:1–1:1–1:6

(ratios more frequently associated with tumor suppression)

Dependent on MSC type and in vivo or in vitro experiment. 1:1 and 1:2 should be used as starting ratios

Cell administration route

Orthotopic/intratumoral, subcutaneous (s.c.), intraperitoneal (i.p), intravenous (i.v.)

Ideally, i.v. if homing also needs to be demonstrated. Otherwise, orthotopic, good for mimicking human carcinogenesis

Timing (latency) of MSC administration

Simultaneously with tumor cells, successive (variable time lag)

Successive (lag depends on type of tumor model; usually 7 days)

Repetition of administration

Single (“one-off”) administration or repeated dosing

Repeated (once or twice); doses > 1 week apart