In the April issue of Experimental Hematology, K. Abe et al. from the University of Tsukuba (Japan) reported their study results on the tumor-initiating potential of leukemic cells derived from GATA1-deficient (Gata1.05) mice. The investigators noted that GATA1 is a transcription factor which regulates proliferation, differentiation and apoptosis during erythropoiesis. Based upon their ability to excluded the Hoescht 33342 dye, the investigators fractionated a side population of stem cells (LSP) from leukemic cells isolated from Gata1.05 mice. One arm of the study involved treating the LSP cells with 5-fluorouracil (5-FU). Similar to hematopoietic stem cells, the fractionated LSP were isolated in a quiescent state. However, upon exposure to 5-FU, the LSP cells reentered the cell cycle and engrafting these cells into nude mice generated erythroblastic leukemia in the recipients. The authors concluded, based upon their observations, that the "distinct self-renewal regulatory mechanisms in LSCs may be considered as one of the causes of worsening of the features of leukemia after injury and relapse." (Moreover, drug-induced activation of the quiescent LSCs may exacerbate the disease state.)

In the March 12th online edition of Stem Cells, Australian scientists D. L. Worthley et al. from the Queensland Institute of Med. Res. (Brisbane) reported their findings on the contributions of bone marrow-derived hematopoietic stem cells (HSCs) to human neoplasia and the perineoplastic stroma. Utilizing the bone marrow tumor registry of female recipients receiving an allogeneic HSC transplant from male donors, the investigators found that 18 cases in which 2 gastric cancers, several skin cancers, and one rectal adenoma were found in the patients post transplantation. With in situ hybridization and immunohistochemistry, the researchers determined that the neoplasia originated from the donor. Additionally, it was found that the bone marrow-derived neoplasia-associated myofibroblasts were identified in the rectal adenoma and in gastric cancer. The authors concluded that "bone marrow-derived cells can generate myofibroblasts in the setting of human gastrointestinal neoplasia."

In the March 5th online edition of PNAS, L. S. Sasportas et al. from Mass. General Hospital and Harvard Medical School explore the potential of using murine mesenchymal stem cells (MSCs) as cell-based delivery vehicles for anti-cancer agents. The investigators reported that the engineered MSCs demonstrated therapeutic efficacy in treating highly invasive gliobastoma in mice. The engineered MSCs retained their "stem-like" properties concomitant with extensive migration to the gliomas. Cells engineered to express the tumor necrosis factor apoptosis ligand (TRAIL) induced caspase-mediated apoptosis in vitro in both glioma cell lines and CD133+ cells isolated from primary tumors. The researchers also demonstrated that there was a profound anti-tumor effect with engineered MSCs delivering recombinant TRAIL against human gliomas implanted into immunosuppressed mice. The authors concluded that their "study demonstrates the efficacy of diagnostic and therapeutic MSC in preclinical glioma models and forms the basis for developing stem cell-based therapies for different cancers."