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 (IFN-
) 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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(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;96:1593603.
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