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Table 2 Contribution of experimental parameters/variables on cytotherapy outcome. The following parameters were examined

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

A. Tumor suppression vs. cancer cell lines (in vivo/in vitro)

 MSC

Breast cancer cell line

MCF-7

MDA-MB-231

All cell lines

 BM/AT/UC

17/ND/75 (75)

0/ND/60 (85.7)

36/20/56.3 (82)

 All MSC

36

46

34.4

B. Tumor suppression vs. cell administration scheme (in vivo)

 MSC

In vivo cell administration scheme

Co-injection of MSC + cancer cells

Administration of MSC in established tumors

 BM/AT/UC

11.8 (50)/10 (0)/ND

64.7 (72.7)/50 (100)/64 (66.7)

 All MSC

14.3 (25)

61.5 (75)

C. Tumor suppression vs. MSC: cancer cell ratio (in vivo)

 MSC

MSC: cancer cell ratio (in vivo)

MSC: cancer < 1

MSC: cancer ≥ 1

 BM/AT/UC

36.4/33.3/71.2

25/12.5/66.7

 All MSC

45.8

30

D.

Consensus of in vivo cytotherapy experiments

Effect on tumor

MSC type

Mouse model

Admin. route

MSC dosage (millions)

Ratio (MSC to cancer cells)

Repeated dosing

Effector-target overlap period (days)

Total experiment duration (days)

ANTI- (N = 19)

NA

NA

NA

1

1:2

NA

22 ± 19

30 ± 23

PRO- (N = 27)

BM

Athymic/nude

s.c./s.c.

1

1:1.35

No repeat

39 ± 22

40 ± 24

  1. A. Type of tumor-specific cell line targeted. Tabulated values denote breast tumor suppression rates (%) caused by MSC after interaction with various breast cancer cell lines, including the two most common ones, MCF-7 and MDA-MB-231, in vitro and/or in vivo. Νumber of experiments N = 11 (MCF-7), 14 (MBA-MB-231), and 32 (all eight cell lines). ND not determined due to insufficient data (N < 5). Numbers in brackets (UC-MSC) correspond to percentage of suppression if neutral effects are not taken into consideration. Data show a more robust tumor suppressive effect of UC-MSC (in italics) which seems be cancer cell line-independent. B. Timing of in vivo cell administration. Tabulated values denote percentages (%) of inhibitory effects caused by MSC on tumors in in vivo experiments, in which MSC were administered either simultaneously (co-infused) with cancer cells in animal models or sequentially in established tumors. The number of experiments recorded for the two modes of administration were N = 27 and 39, respectively. ND not determined due to insufficient data (N < 5). Percentages in brackets: sub-portion of samples in which a strong (over twofold) suppressive effect was observed. Data show that MSC have a more prominent suppressive effect when delivered to pre-established tumors. C. Cell dosing ratio. Tabulated values denote percentages (%) of tumor suppressive effects of MSC in in vivo experiments, depending on the relative number of administered MSC (effector cells) to cancer (target) cells (MSC to cancer ratio). The effects of two such ratios are compared: MSC: cancer < 1 (cancer cells in excess) vs. MSC: cancer ≥ 1 (MSC in excess). Percentages refer to the proportion of experiments with antitumorigenic results out of the total number of experiments in each ratio. The number of experiments recorded for the two ratios were N = 24 and 30, respectively. Data indicate a stronger, by over twofold, tumor suppressive effect of AT-MSC when used at the lower MSC dosing ratio (values in italics). See also section 4.1.3 for further discussion. D. Combination of the typical, most frequently observed (> 50% frequency) parameters of in vivo experiments using naïve MSC. Typical experimental parameters related to anti- or pro-tumorigenic effect of MSC are shown. NA data associated with the respective parameter gave no clear consensus. Highest suppression rates are highlighted in italics (where applicable)
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Stem Cell Research & Therapy

ISSN: 1757-6512