Browsing by Author "Battina, Hanisha L."

Now showing 1 - 3 of 3
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    Characterization and assessment of lung and bone marrow derived endothelial cells and their bone regenerative potential
    (Frontiers, 2022) de Lima Perini, Mariana Moraes; Valuch, Conner R.; Dadwal, Ushashi C.; Awosanya, Olatundun D.; Mostardo, Sarah L.; Blosser, Rachel J.; Knox, Adam M.; McGuire, Anthony C.; Battina, Hanisha L.; Nazzal, Murad; Kacena, Melissa A.; Li, Jiliang; Biology, School of Science
    Angiogenesis is important for successful fracture repair. Aging negatively affects the number and activity of endothelial cells (ECs) and subsequently leads to impaired bone healing. We previously showed that implantation of lung-derived endothelial cells (LECs) improved fracture healing in rats. In this study, we characterized and compared neonatal lung and bone marrow-derived endothelial cells (neonatal LECs and neonatal BMECs) and further asses3sed if implantation of neonatal BMECs could enhance bone healing in both young and aged mice. We assessed neonatal EC tube formation, proliferation, and wound migration ability in vitro in ECs isolated from the bone marrow and lungs of neonatal mice. The in vitro studies demonstrated that both neonatal LECs and neonatal BMECs exhibited EC traits. To test the function of neonatal ECs in vivo, we created a femoral fracture in young and aged mice and implanted a collagen sponge to deliver neonatal BMECs at the fracture site. In the mouse fracture model, endochondral ossification was delayed in aged control mice compared to young controls. Neonatal BMECs significantly improved endochondral bone formation only in aged mice. These data suggest BMECs have potential to enhance aged bone healing. Compared to LECs, BMECs are more feasible for translational cell therapy and clinical applications in bone repair. Future studies are needed to examine the fate and function of BMECs implanted into the fracture sites.
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    Interaction of the inflammatory response and megakaryocytes in COVID-19 infection
    (Elsevier, 2021-09) Battina, Hanisha L.; Alentado, Vincent J.; Srour, Edward F.; Moliterno, Alison R.; Kacena, Melissa A.; Orthopaedic Surgery, School of Medicine
    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly across the world and has resulted in more than 4.2 million global deaths as of July 30, 2021. For reasons that remain unknown, the coronavirus disease 2019 (COVID-19) clinically manifests itself in various levels of severity, with most patients positive for COVID-19 being asymptomatic or having only mild symptoms. However, clinical studies in severely ill patients have implicated that manifestations of this infection are due in part to abnormal megakaryocyte (MK) behavior. Additionally, COVID-19–associated cytokine storms have been found to induce aberrant MK formation, primarily through interleukin-6 and Janus kinase-signal transducer and activator of transcription signaling. Autopsy reports have revealed significantly higher rates of MKs in the pulmonary and cardiac systems, which may be responsible for the high rate of thrombotic complications and abnormal coagulopathies in patients with severe forms of COVID-19. This review examines MKs and their potential function in the clinical manifestations of SARS-CoV-2 infection.
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    The Effects of Bone Morphogenetic Protein 2 and Thrombopoietin Treatment on Angiogenic Properties of Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice
    (Wiley, 2021) Dadwal, Ushashi C.; Bhatti, Fazal Ur Rehman; Awosanya, Olatundun D.; Nagaraj, Rohit U.; Perugini, Anthony J., III.; Sun, Seungyup; Valuch, Conner R.; Staut, Caio de Andrade; Mendenhall, Stephen K.; Tewari, Nikhil P.; Mostardo, Sarah L.; Nazzal, Murad K.; Battina, Hanisha L.; Zhou, Donghui; Kanagasabapathy, Deepa; Blosser, Rachel J.; Mulcrone, Patrick L.; Li, Jiliang; Kacena, Melissa A.; Orthopaedic Surgery, School of Medicine
    With an aging world population, there is an increased risk of fracture and impaired healing. One contributing factor may be aging-associated decreases in vascular function; thus, enhancing angiogenesis could improve fracture healing. Both bone morphogenetic protein 2 (BMP-2) and thrombopoietin (TPO) have pro-angiogenic effects. The aim of this study was to investigate the effects of treatment with BMP-2 or TPO on the in vitro angiogenic and proliferative potential of endothelial cells (ECs) isolated from lungs (LECs) or bone marrow (BMECs) of young (3-4 months) and old (22-24 months), male and female, C57BL/6J mice. Cell proliferation, vessel-like structure formation, migration, and gene expression were used to evaluate angiogenic properties. In vitro characterization of ECs generally showed impaired vessel-like structure formation and proliferation in old ECs compared to young ECs, but improved migration characteristics in old BMECs. Differential sex-based angiogenic responses were observed, especially with respect to drug treatments and gene expression. Importantly, these studies suggest that NTN1, ROBO2, and SLIT3, along with angiogenic markers (CD31, FLT-1, ANGPT1, and ANGP2) differentially regulate EC proliferation and functional outcomes based on treatment, sex, and age. Furthermore, treatment of old ECs with TPO typically improved vessel-like structure parameters, but impaired migration. Thus, TPO may serve as an alternative treatment to BMP-2 for fracture healing in aging owing to improved angiogenesis and fracture healing, and the lack of side effects associated with BMP-2.