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Browsing by Author "Chen, Xiaoping"
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Item The Axolotl Fibula as a Model for the Induction of Regeneration across Large Segment Defects in Long Bones of the Extremities(Public Library of Science, 2015) Chen, Xiaoping; Song, Fengyu; Jhamb, Deepali; Li, Jiliang; Bottino, Marco C.; Palakal, Mathew J.; Stocum, David L.; Department of Biology, School of ScienceWe tested the ability of the axolotl (Ambystoma mexicanum) fibula to regenerate across segment defects of different size in the absence of intervention or after implant of a unique 8-braid pig small intestine submucosa (SIS) scaffold, with or without incorporated growth factor combinations or tissue protein extract. Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone. By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases. These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process.Item Axolotl Xenografts Improve Regeneration of Xenopus Hind Limbs(Office of the Vice Chancellor for Research, 2013-04-05) Chen, Xiaoping; Stocum, David L.Axolotls regenerate perfect copies of amputated limbs, whereas Xenopus froglet limbs regenerate only a spike of cartilage. We asked whether axolotl muscle and cartilage xenografted from normal or GFP-labeled limbs to amputated froglet limbs, with or without treatment with cyclosporin A (CSA) and/or retinoic acid (RA), would improve Xenopus limb regeneration via the release of regeneration-promoting factors into the host limb tissue. The grafted froglet limbs were allowed to regenerate for three months to two years. We detected initial symptoms of graft vs. host disease with or without CSA treatment that subsequently disappeared. The grafted limbs first formed a spike that subsequently grew wider at the tip and after three months began to separate into 2-5 digit-like structures that continued to grow. CSA and low-dose RA treatment decreased the time at which digit formation could be detected but were not necessary for digit formation. The digit pattern was not asymmetric, thus individual digits were not identifiable. Immature muscle was detected in the regenerated limbs by trichrome and MF-20 antibody staining, and nerve fibers were detected by Luxol Fast Blue staining. In one limb with a GFP graft, a few axolotl cells were detected around the base of the digits that may have stimulated digit separation. Although the mechanism of digit formation remains obscure, we conclude that factors released by degraded axolotl tissue or surviving axolotl cells can stimulate complex tissue regeneration and initiate the first step of digital anterior-posterior pattern formation in regenerating Xenopus hind limbs. These results have significance for the possibility of stimulating the regeneration of complex mammalian structures that have been injured by trauma or disease.Item The New Treatment of Osteosarcoma by Biologic Response Modifiers(Office of the Vice Chancellor for Research, 2016-04-08) Chen, Xiaoping; Zhao, Huadong; Cheng, LiangOsteosarcoma is a kind of bone cancer mainly affecting children and young adults and is lethal in about a third of cases. The treatment of osteosarcoma has evolved greatly during the last 40 years, however, the great progress that was seen in the 1970s and early 1980s has since stalled. The main challenge now is that advanced combination treatment can’t continue prolong the survival. Based on the micro-metastatic disease related to shorter survival, biologic response modifiers become a new treatment which can stimulate the immune system to eradicate minimal residual disease post-surgery, chemotherapy and radiotherapy. This kind immune treatment may improve the disease-free and long-term survival rates of patients. Mifamurtide is a novel biologic response modifier which is indicated for the treatment of highgrade, non-metastasizing, resectable osteosarcoma following complete surgical removal in children, adolescents, and young adults. In our study, we searched for non-phase l Mifamurtide clinical studies on osteosarcoma through Medline, Google Scholar, and Clinical Trial Government Database. Among six clinical studies we found, two phase ll trials, one phase lll trial, one patient-access study, one decision study, and one cohort study. We systematically analyzed these studies and further evaluated the efficacy, side effects and safety of Mifamurtide on osteosarcoma.