Table 1.
Studies Identifying MSCs | Authors Questioning The MSC Model | |||||||
---|---|---|---|---|---|---|---|---|
Study | Schatton et al. Nature 2008 | Kupas et al. J Invest Dermatol. 2011 | Boiko et al. Nature 2010 | Civenni et al. Cancer Res. 2011 | Boonyaratanakornkit et al. J Invest Dermatol. 2010 | Luo et al. Stem Cells 2012 | Quintana et al. Nature 2008 | Quintana et al. Cancer Cell 2010 |
Marker | ABCB5 | RANK (ABCB5+) | CD271 | CD271 | ALDH | ALDH | Multiple | CD271, ABCB5 |
Trypsin Dissociation | No | No | No | No | No | No | Yes | Yes |
Sorting Technique | Magnetic Beads | FACS | FACS | FACS | FACS | FACS | FACS | FACS |
Matrix | None | None reported | Matrigel | Matrigel | None reported | Matrigel | Matrigel | Matrigel |
Host Strain | NOD/SCID | NSG | Rag2−/−gc−/− | NOD/SCID NSG | NOD/SCID NSG | NOD/SCID NSG | NSG | NSG |
Transplant Rounds | 2 | 1 | 2 | 3 | 2–3 | 3 | 1–2 | 2 |
Marker(+)MSC Enrichment | Yes | Yes | Yes | Yes | Yes | Yes | No | No |
Genetic Lineage Tracing | Yes | No | No | No | No | No | No | No |
Noteworthy differences in protocols include the use of trypsin, the degree of immunosuppression in animal xenograft carriers, and use of the melanoma cell stimulant, laminin, in the form of Matrigel. In the absence of trypsin to harvest cells (trypsin cleaves ABCB5 and CD271 from cells, as shown by Civenni et al. (Civenni et al., 2011)), multiple independent researchers have observed the existence of cells that comply with the definition of MSCs (there is a potential for false negatives due to trypsin proteolytic cleavage of cell-surface markers). Comparison of highly immunocompromised NSG mice to NK-depleted nude or NOD/SCID mice has also revealed that in the former (1) the parental melanoma heterogeneity could not be recapitulated, and (2) CD271− cells may form tumors in the first round but may not be serially passaged, as would be anticipated for MSCs.