Browsing by Subject "thrombopoietin"

Now showing 1 - 4 of 4
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    Benchside to Bedside: The Launching of a Novel Bone Healing Agent
    (Office of the Vice Chancellor for Research, 2013-04-05) Bemenderfer, Thomas; Busenbark, John; Kansal, Jagan; Chu, Tien-Min Gabriel; Kacena, Melissa A.
    The ability to evolve a nascent idea into a successful entity requires navigation through a number of perils known to debilitate new ventures. Embryonic firms (or ideas) require sufficient development; from establishing an unambiguous approach, to attaining the necessary capital for evolution and growth, to fostering an environment and market for the idea or product. In the venture community, there are a number of advocates who possess the ability to contribute to new ventures (e.g. venture community support functions, venture capitalists, or informal contributors), and these individuals help navigate the startup or idea through inception to effectuation. Academic faculty, though, who often are not engrained into the local venture community, are frequently disadvantaged because their ideas or new firms come as an ancillary to their primary work. Already potentially impeded by the challenges presented by the legal constraints of providing sufficient equity for ideas to the university, developing a clear, effective path to market can be difficult for academic faculty. In addition to the systemic uncertainty, difficulty, and impediments faced by all entrepreneurs, academic faculty are constrained by limited time, funding, experience, and other resources – all related to their inclusion in the university or system. In order to alleviate these constraints and propel cutting-edge scientific breakthroughs and technological development, Innovation-to-Enterprise Central (ITEC) was initiated to assist academic faculties’ developments into the market – where, ultimately, these products will have the greatest utility to society. Osetofuse is an embryonic firm in the nascent stages of conceptualizing a revolutionary new product, which uses thrombopoietin as a novel bone healing agent. Through the ITEC program, Osteofuse has been able to facilitate the exploration of the potential value (clinically, economically, and societally) of its research and how the initial idea can be developed into a commercialized and monetized product. In the process, it has developed mechanisms to gauge the market’s acceptance of the product, the intellectual property and legal issue constraints facing the idea, potential commercialization streams and related valuations for marketization, and a quantitative analysis of projected revenue provisions. ITEC fosters continual compounding of knowledge capacity, as the trajectory of Osteofuse has not only inclined, but redirected because of specific uncovered data and insight from the program. As a result, Osteofuse has undergone dramatic transformation; in terms of both its formal identity and the potential approach to the market.
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    Effects of Thrombopoietin (TPO) on Longitudinal Mouse Hind Limb Crush Injury Model
    (Office of the Vice Chancellor for Research, 2014-04) Rothchild, Greg; Lipking, Kelsey; McKinley, Todd; Kacena, Melissa A.; Sandusky, George E.
    Approximately 645 people suffer from blunt force trauma injury to the femur every day. The recovery time of such injury can last anywhere from 3-6 months. Thrombopoietin (TPO) was used as a growth factor to induce bone and muscle healing. In this study, nine separate mouse groups (10 mice per group) were used: Crush PBS, Crush TPO, Surgery PBS, and Surgery TPO at day 3 and day 17, and controls with no surgery/crush/treatment. Skeletal muscle was harvested from the following sites: experimental impact, experimental adjacent, and normal contralateral skeletal muscle as a control. The muscles were fixed, processed, sectioned, and stained with H&E and Massons Trichrome stains. The slides were reviewed for skeletal muscle injury, muscle necrosis, inflammation, muscle repair, and regeneration. In addition, F4/80, an immunostain for macrophages was performed. On microscopic examination at day 3 the most common histologic changes seen were sporadic muscle fiber vacuolation, focal necrosis of varying sizes, muscle contraction bands, and infiltration of macrophages. On day 17, the skeletal muscle injury was generally healed. The main histologic lesions seen were variable sizes of muscle fibers, early fibroplasia, fat infiltration, some macrophages, satellite cells, and neovascularization. Comparing the TPO treated mice versus the PBS control group, the lesions at both time points were less in the TPO treated mice.
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    Megakaryocytes promote osteoclastogenesis in aging
    (Impact Journals, 2020-07-07) Kanagasabapathy, Deepa; Blosser, Rachel J.; Maupin, Kevin A.; Hong, Jung Min; Alvarez, Marta; Ghosh, Joydeep; Mohamad, Safa F.; Aguilar-Perez, Alexandra; Srour, Edward F.; Kacena, Melissa A.; Bruzzaniti, Angela; Orthopaedic Surgery, School of Medicine
    Megakaryocytes (MKs) support bone formation by stimulating osteoblasts (OBs) and inhibiting osteoclasts (OCs). Aging results in higher bone resorption, leading to bone loss. Whereas previous studies showed the effects of aging on MK-mediated bone formation, the effects of aging on MK-mediated OC formation is poorly understood. Here we examined the effect of thrombopoietin (TPO) and MK-derived conditioned media (CM) from young (3-4 months) and aged (22-25 months) mice on OC precursors. Our findings showed that aging significantly increased OC formation in vitro. Moreover, the expression of the TPO receptor, Mpl, and circulating TPO levels were elevated in the bone marrow cavity. We previously showed that MKs from young mice secrete factors that inhibit OC differentiation. However, rather than inhibiting OC development, we found that MKs from aged mice promote OC formation. Interestingly, these age-related changes in MK functionality were only observed using female MKs, potentially implicating the sex steroid, estrogen, in signaling. Further, RANKL expression was highly elevated in aged MKs suggesting MK-derived RANKL signaling may promote osteoclastogenesis in aging. Taken together, these data suggest that modulation in TPO-Mpl expression in bone marrow and age-related changes in the MK secretome promote osteoclastogenesis to impact skeletal aging.
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    Thrombopoietin: A Novel Bone Healing Agent
    (Office of the Vice Chancellor for Research, 2013-04-05) Engle, Andrew; Bemenderfer, Thomas; Bethel, Monique; Millikan, Patrick D.; Wessel, Alexander R.; Cheng, Ying-Hua; Wilhite, Jonathan H.; Chu, Tien-Min Gabriel; Kacena, Melissa A.
    Critical-size defects in bones do not heal spontaneously and usually require the use of grafts. Unfortunately, grafts have several limitations. To improve bone formation, many clinicians now use bone morphogenetic proteins (BMP), particularly in spinal fusion, fracture healing, and in critical-size defect regeneration. However, multiple side effects of BMP treatment have been uncovered including increased incidence of cancer. Thus, there is great interest in alternatives that allow for safe and effective bone regeneration. Here we show the ability of thrombopoietin (TPO), the main megakaryocyte growth factor, to heal critical-size femoral defects rodents. 5mm or 4mm segmental defects were created in the femur of Long Evans rats or C57BL/6 mice, respectively. The defects were filled with a novel bioabsorbable scaffold which was loaded with recombinant human TPO, BMP-2, or saline, and held stable by a retrograde 1.6 mm intramedullary Kirschner wire (rats) or 23G needle (mice). Xrays were taken every 3 weeks in rats and weekly in mice. Animal were sacrificed at 15 weeks, at which time micro-computed tomography (μCT) and histological analyses were performed. The results observed in mice and rats were similar. The saline control group did not show bridging callus at any time. Both the BMP-2 and TPO groups healed the defect, although bridging callus was evident at earlier times in the BMP-2 groups. However, the TPO groups showed a much more remodeled and physiologic contour on both Xray and μCT. μCT and histological analysis confirms that compared to BMP-2, TPO-treated specimens have a thicker cortex but smaller diameter and smoother contour. TPO appears to restore the original bone contour by stimulating osteoblastogenesis, allowing for periosteal bridging and stabilization to occur, while simultaneously stimulating osteoclast formation. Thus, TPO may serve as a novel bone healing agent.