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JNCI Journal of the National Cancer Institute 2005 97(7):540-541; doi:10.1093/jnci/dji088
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© 2005 Oxford University Press

CORRESPONDENCE

Re: Mesenchymal Stem Cells: Potential Precursors for Tumor Stroma and Targeted-Delivery Vehicles for Anticancer Agents

Dominik Wolf, Holger Rumpold, Ruth Koeck, Eberhard Gunsilius

Affiliation of authors: Department of Hematology and Oncology, Medical University Innsbruck, Innsbruck, Austria

Correspondence to: Eberhard Gunsilius, MD, Laboratory of Angiogenesis and Tumor Biology, Department of Hematology and Oncology, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria (e-mail: eberhard.gunsilius{at}uibk.ac.at).

In the November 3, 2004, issue of the Journal, Studeny et al. (1) showed intriguing data on the use of human bone marrow (BM)–derived mesenchymal stem cells (MSCs) for the selective delivery of interferon {beta} (IFN-{beta}) to pulmonary metastases. However, we have concerns regarding their experimental system. A xenogenic model (i.e., human MSCs, human tumors grown in immunodeficient mice) to demonstrate selective homing of systemically injected human MSCs might be too artificial to be relevant to the in vivo clinical situation. We injected syngeneic BM-derived MSCs into BALB/c mice bearing pulmonary metastases induced by injection of murine renal carcinoma (RenCa) cells. We detected MSCs in the vicinity of the tumors (mainly in larger tumor nodules) and within the tumors (in metastases with smaller diameter). We also found a large number of the injected MSCs in the spleen, in the liver, and in normal lung tissue surrounding the pulmonary metastases (Fig. 1). This marked difference in the homing behavior of MSCs between these two experimental models may be explained by the fact that human tumors selectively attract human MSCs by their secretion of human-specific chemoattractants. In addition, in the xenogenic model, human MSCs that do not reach the tumor nodules (i.e., human MSCs implanted in xenogenic mouse tissue) might undergo cell death, whereas they are able to survive when implanted in syngeneic tissues.



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  		Fig. 1. Primary mesenchymal stem cells (MSCs) were generated from bone marrow cells isolated from BALB/c mice and labeled with the fluorescent dye PKH26 after passage 3. Pulmonary metastases were induced by intravenous injection of 106 murine renal carcinoma (RenCa) cells into BALB/c mice. On day 10 and day 15 after tumor cell injection, the mice were injected intravenously with 106 labeled MSCs. On day 20 after tumor cell injection, the mice were injected with fluorescein isothiocyanate–labeled lectin 5 minutes prior to euthanasia to visualize blood vessels. Mouse organs (spleen, liver, and lung) were preserved for fluorescence microscopy analysis. The green fluorescence represents vessel staining to highlight the anatomy of the different organs (left panel); the red fluorescence shows PKH-labeled MSCs on the same section (right panel). Yellow fluorescence derives from very intense PKH-stained MSCs and is thought to be nonspecific in the green channel. Injected MSCs are detectable in the spleen (A and B) as well as in the liver (C and D), whereas both organs are free of tumor nodules. Pulmonary metastases with large diameter are surrounded by labeled MSCs (E and F), whereas smaller metastases are infiltrated by MSCs (right metastasis in panels G and H). Dotted lines and arrows depict borders of pulmonary metastases. Magnification: spleen, x100; liver and lung, x200.

 
REFERENCES

(1) Studeny M, Marini FC, Dembinski JL, Zompetta C, Cabreira-Hansen M, Bekele BN, et al. Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst 2004;96:1593–603.[Abstract/Free Full Text]


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Response to this Correspondence

RESPONSE: Re: Mesenchymal Stem Cells: Potential Precursors for Tumor Stroma and Targeted-Delivery Vehicles for Anticancer Agents
Frank Marini, Matus Studeny, and Michael Andreeff
J Natl Cancer Inst 2005 97: 541-542. [Extract] [Full Text] [PDF]




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