No abstract

Bone augmentation via tissue engineering has generated significant interest. We hypothesized that periosteum-derived cells could be used in place of bone marrow stromal cells (which are widely used) in bone engineering, but the differences in osteogenic potential between these 2 cell types are unclear. Here, we compared the osteogenic potential of these cells, and investigated the optimal osteoinductive conditions for periosteum-derived cells. Both cell types were induced, via bFGF and BMP-2, to differentiate into osteoblasts. Periosteal cells proliferated faster than marrow stromal cells, and osteogenic markers indicated that bone marrow stromal cells were more osteogenic than periosteal cells. However, pre-treatment with bFGF made periosteal cells more sensitive to BMP-2 and more osteogenic. Transplants of periosteal cells treated with BMP-2 after pre-treatment with bFGF formed more new bone than did marrow stromal cells. Analysis of these data suggests that combined treatment with bFGF and BMP-2 can make periosteum a highly useful source of bone regeneration.

Both tolerance to nutrient starvation and angiogenesis are essential for cancer progression because of the insufficient supply of nutrients to tumor tissue. Since chronic nutrient starvation seldom occurs in normal tissue, cancer's tolerance to nutrient starvation should provide a novel target for cancer therapy. In this study, we propose an anti-austerity strategy to exploit the ability of agents to eliminate cancer cells' tolerance to nutrient starvation. We established a simple screening method for agents that inhibit cancer cell viability preferentially during nutrient starvation, using PANC-1 cell line cultured in nutrient-rich and nutrientdeprived media. ancers always have deformed, deficient vascular and lymphatic systems due to excessive and unregulated tumor cell growth, as well as improper and insufficient angiogenesis. As a result, perfusion within cancers is inadequate, and the cancers contain regions that are transiently and chronically exposed to nutrient starvation. 1) These microenvironmental inadequacies are present from the earliest stage in the development of cancers, and are fully established while the neoplasm is still microscopic in size. 2) Since nutrient starvation occurs in tumor tissue that is >100-200 µm away from a functional blood supply, 3) tumor survival depends, in part, on the ability to recruit new blood microvessels via angiogenic factors. This affords tumor cells the ability to survive and propagate in a hostile environment, 4) and thus increased angiogenesis by a malignancy is related to a poor prognosis. 5,6) Because of this, antiangiogenic therapy was postulated to be the most promising and specific approach to cancer therapy. Already, extensive studies have been conducted in an attempt to prevent tumor angiogenesis.However, Yu et al. recently suggested that tumors may be able to elude the effect of angiogenesis inhibitors, since antiangiogenic therapy targets genetically stable endothelial cells in the tumor vasculature, and genetic alterations that decrease the vascular dependence of tumor cells can influence the response of tumors to this therapy. 7) The well-known observation that hypovascularity is an outstanding characteristic of pancreatic cancers in diagnostic images suggests that pancreatic cancer tissue has a poor blood supply. 8) However, since pancreatic cancers are known to be among the most aggressive malignancies despite their poor blood supply, we proposed that cancer cells' tolerance of insufficient nutrient might be an important determinant of malignancy. 9) Although the mechanism of tolerance has not yet been fully elucidated, the PI-3K-Akt pathway and AMPK have been found to be involved. 10) Because the blood supply of normal tissue is regulated in a sophisticated manner, angiogenesis is seldom activated in normal healthy adult tissues, except in the female reproductive system. 11) The same is true for nutrient starvation. We therefore speculated that if some compound could abolish cancer cells' tolerance of nutrient starvation, it might be capable of be...