Fig. 1Effects of mesenchymal stromal cells (MSC) on in vitro proliferation of human fibrosarcoma cells (HT1080). (A) In vitro growth kinetics of HT1080 cells in the presence of human-MSC (hMSC) are significantly enhanced compared to cells grown in the absence of hMSC. (B) The change is about 80-fold for hMSC-cocultures HT1080, but 40-fold for HT1080 alone. (C) Representative cell densities of cultured cells. Irradiated hMSCs show little change between cultures on days 2 and 5. ap<.05 by student's t-test.
Fig. 2Effects of mesenchymal stromal cells (MSC) on in vivo proliferation and invasion of various sarcoma cell types. Tumors of the MSC-treated groups of human sarcoma cells in NOG/SCID mice (A-C), mouse sarcoma cells in Sprague-Dawley rats (D-F), and rat sarcoma cells in C57BL/6 mice (G-I) show significantly increased and highly infiltrative growth compared with controls. Human MSC alone does not form tumors. HT1080, human sarcoma cell; WEHI164, mouse sarcoma cell; RR1022, rat sarcoma cell; hMSC, human mesenchymal stromal cell; mMSC, mouse mesenchymal stromal cell; rMSC, rat mesenchymal stromal cell. ap=.035, bp=.14, and cp=.050 by Student's t-test.
Fig. 3Effects of mesenchymal stromal cells (MSC) on invasion and metastasis in NOG/SCID mice bearing 5FU cells, a human gastric cancer cell line. Subcutaneous inoculation of 5FU alone results in compact expansile growth without lung metastasis (upper panels), whereas 5FU combined with human MSC (hMSC) shows marked desmoplastic and infiltrative growth and lung metastasis, highlighted by immunostaining for cytokeratin (lower panels). CK, cytokeratin.
Table 1.Colony-forming cell (CFC) assay
Cell |
CFC frequency |
10,000 CFC equivalent |
HT1080 |
1/5 cells (20) |
5 × 104 cells |
WEHI164 |
1/4 cells (25) |
4 × 104 cells |
RR1022 |
1/1.5 cells (66.6) |
1.5 × 104 cells |
Table 2.The effects of MSCs on in vivo growth characteristics of various sarcoma cells
Cell |
Host animal |
Co-injection (1 × 105) |
n |
Day sacrificed |
Tumor volume (mean ± SD, mm3) |
Growth pattern |
p-value |
HT1080 (5 × 104) |
NOG/SCID |
hMSC |
6 |
14 |
62.01 ± 28.83 |
Infiltrative |
.035 |
|
|
- |
6 |
14 |
30.08 ± 25.74 |
Expansile |
|
WEHI164 (4 × 104) |
Spague-Dawley |
mMSC |
4 |
21 |
108.68 ± 134.09 |
Infiltrative |
.141 |
|
|
- |
3 |
21 |
16.12 ± 18.48 |
Expansile |
|
RR1022 (1.5 × 104) |
C57BL/6 |
rMSC |
3 |
14 |
120.46 ± 63.81 |
Infiltrative |
.050 |
|
|
- |
2 |
14 |
8.58 ± 5.51 |
Expansile |
|