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

From: Mesenchymal stem cells in preclinical cancer cytotherapy: a systematic review

Contributing parameters to outcome disparity of MSC-based cancer cytotherapy Variability range of differentially expressed parameters Proposed optimal experimental parameter
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