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BackgroundBone marrow aspirate concentrate (BMAC) including high densities of stem cells and progenitor cells may possess a stronger bone regenerative capability compared with Platelet-rich plasma (PRP), which contains enriched growth factors. The objective of this study was to evaluate the effects of human BMAC and PRP in combination with β-tricalcium phosphate (β-TCP) on promoting initial bone augmentation in an immunodeficient mouse model.Methodology/Principal FindingsBMAC and PRP were concentrated with an automated blood separator from the bone marrow and peripheral blood aspirates. β-TCP particles were employed as a scaffold to carry cells. After cell counting and FACS characterization, three groups of nude mice (BMAC+TCP, PRP+TCP, and a TCP control) were implanted with graft materials for onlay placement on the cranium. Samples were harvested after 4 weeks, and serial sections were prepared. We observed the new bone on light microscopy and performed histomorphometric analysis. After centrifugation, the concentrations of nucleated cells and platelets in BMAC were increased by factors of 2.8±0.8 and 5.3±2.4, respectively, whereas leucocytes and platelets in PRP were increased by factors of 4.1±1.8 and 4.4±1.9, respectively. The concentrations of CD34-, CD271-, CD90-, CD105-, and CD146-positive cells were markedly increased in both BMAC and PRP. The percentage of new bone in the BMAC group (7.6±3.9%) and the PRP group (7.2±3.8%) were significantly higher than that of TCP group (2.7±1.4%). Significantly more bone cells in the new bone occurred in sites transplanted with BMAC (552±257) and PRP (491±211) compared to TCP alone (187±94). But the difference between the treatment groups was not significant.Conclusions/SignificanceBoth human BMACs and PRP may provide therapeutic benefits in bone tissue engineering applications. These fractions possess a similar ability to enhance early-phase bone regeneration.

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Although cytostatin analog protein phosphatase 2A (PP2A)-specific inhibitors are promising candidates of a new type of anticancer drug, their development has been hindered because of their liability. To find new classes of PP2A-specific inhibitors, we conducted a screening with microbial metabolites and found that rubratoxin A, a classical mycotoxin, is a highly specific and potent inhibitor of the enzyme. While rubratoxin A inhibits PP2A at Ki = 28.7 nM, it hardly inhibited any other phosphatases examined. Rubratoxin B, a close analog, also specifically but weakly inhibits PP2A at Ki = 3.1 lM. The inhibition of intracellular PP2A in cultured cells is obviously observed with 20 lM rubratoxin A treatment for 3 h, inducing the overphosphorylation in PP2A substrate proteins. Although rubratoxins and cytostatin differ in the apparent structures, these compounds share similarities in the structures in detail and PP2A-binding manners. Rubratoxin A showed higher suppression of tumor metastasis and reduction of the primary tumor volume than cytostatin in mouse experiments. As a successor of cytostatin analogs, rubratoxin A should be a good compound leading to the development of antitumor drugs targeting PP2A. (Cancer Sci 2010; 101: 743-750) T he phosphorylation of intracellular protein plays a central role in the regulation of eukaryotic cell function and metabolism. Protein phosphatase (PP)2A is a ubiquitous serine ⁄ threonine phosphatase in eukaryotic cells, which regulates the phosphorylation state and function of a broad range of proteins.(1,2) We previously isolated a PP2A-specific inhibitor, cytostatin, from an actinomycete culture.(3-5) Its analog, fostriecin, and other PP2A-specific inhibitors have also been reported since mid 1990s.(6-11) These new inhibitors have higher specificities to PP2A than okadaic acid, a previously identified inhibitor (PP1 IC 50 ⁄ PP2A IC 50 : fostriecin, 10 4

Targeting stroma in tumor tissues is an attractive new strategy for cancer treatment. We developed in vitro coculture system, in which the growth of human prostate cancer DU-145 cells is stimulated by prostate stromal cells (PrSC) through insulin-like growth factor I (IGF-I). Using this system, we have been searching for small molecules that inhibit tumor growth through modulation of tumor-stromal cell interactions. As a result, we have found that leucinostatins and atpenins, natural antifungal antibiotics, inhibit the growth of DU-145 cells cocultured with PrSC more strongly than that of DU-145 cells alone. In this study we examined the antitumor effects of these small molecules in vitro and in vivo. Growing evidence indicates that the stroma plays a critical role in the growth and metastasis of various cancers, including colorectal, 1 breast, 2,3 pancreatic 4 and prostate cancer.