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Item 15. Augmentation of homing of cord blood stem cells(Elsevier, 2005-11) Broxmeyer, H.E.; Christopherson, K.W.; Hangoc, G.; Campbell, T.B.; Medicine, School of MedicineItem 6: Effect of CD26 on Cord Blood, and Other Means to Enhance Engraftment of Hematopoietic Stem Cells(E6325, 2007-11-01) Broxmeyer, Hal E.; Medicine, School of MedicineItem Adipose-derived stem cell conditioned medium for the treatment of amyotrophic lateral sclerosis: pre-clinical evidence and potential for clinical application(Medknow Publications, 2019-09) Walker, Chandler L.; Department of Biomedical and Applied Sciences, School of DentistryItem Alternative sources of human pluripotent stem cells(2005-05) President’s Council on Bioethics (U.S.)Discusses the following questions for four sources of stem cells: (1.) "Is it ethically sound?", (2.) "Is is scientifically sound?", (3.) "Is it 'realistic'?".Item Characterization of the Cellular Output of a Point-of-Care Device and the Implications for Addressing Critical Limb Ischemia(Mary Ann Liebert, 2015) Woodell-May, Jennifer E.; Tan, Matthew L.; King, William J.; Swift, Matthew J.; Welch, Zachary R.; Murphy, Michael P.; McKale, James M.; Department of Surgery, IU School of MedicineCritical limb ischemia (CLI) is a terminal disease with high morbidity and healthcare costs due to limb loss. There are no effective medical therapies for patients with CLI to prevent amputation. Cell-based therapies are currently being investigated to address this unmet clinical need and have shown promising preliminary results. The purpose of this study was to characterize the output of a point-of-care cell separator (MarrowStim P.A.D. Kit), currently under investigation for the treatment of CLI, and compare its output with Ficoll-based separation. The outputs of the MarrowStim P.A.D. Kit and Ficoll separation were characterized using an automated hematology analyzer, colony-forming unit (CFU) assays, and tubulogenesis assays. Hematology analysis indicated that the MarrowStim P.A.D. Kit concentrated the total nucleated cells, mononuclear cells, and granulocytes compared with baseline bone marrow aspirate. Cells collected were positive for VEGFR-2, CD3, CD14, CD34, CD45, CD56, CD105, CD117, CD133, and Stro-1 antigen. CFU assays demonstrated that the MarrowStim P.A.D. Kit output a significantly greater number of mesenchymal stem cells and hematopoietic stem cells compared with cells output by Ficoll separation. There was no significant difference in the number of endothelial progenitor cells output by the two separation techniques. Isolated cells from both techniques formed interconnected nodes and microtubules in a three-dimensional cell culture assay. This information, along with data currently being collected in large-scale clinical trials, will help instruct how different cellular fractions may affect the outcomes for CLI patients.Item Combined local delivery of tacrolimus and stem cells in hydrogel for enhancing peripheral nerve regeneration(Wiley, 2021-07) Saffari, Tiam M.; Chan, Katelyn; Saffari, Sara; Zuo, Kevin J.; McGovern, Renee M.; Reid, Joel M.; Borschel, Gregory H.; Shin, Alexander Y.; Medicine, School of MedicineThe application of scaffold-based stem cell transplantation to enhance peripheral nerve regeneration has great potential. Recently, the neuroregenerative potential of tacrolimus (a U.S. Food and Drug Administration-approved immunosuppressant) has been explored. In this study, a fibrin gel-based drug delivery system for sustained and localized tacrolimus release was combined with rat adipose-derived mesenchymal stem cells (MSC) to investigate cell viability in vitro. Tacrolimus was encapsulated in poly(lactic-co-glycolic) acid (PLGA) microspheres and suspended in fibrin hydrogel, using concentrations of 0.01 and 100 ng/ml. Drug release over time was measured. MSCs were cultured in drug-released media collected at various days to mimic systemic exposure. MSCs were combined with (i) hydrogel only, (ii) empty PLGA microspheres in the hydrogel, (iii) 0.01, and (iv) 100 ng/ml of tacrolimus PLGA microspheres in the hydrogel. Stem cell presence and viability were evaluated. A sustained release of 100 ng/ml tacrolimus microspheres was observed for up to 35 days. Stem cell presence was confirmed and cell viability was observed up to 7 days, with no significant differences between groups. This study suggests that combined delivery of 100 ng/ml tacrolimus and MSCs in fibrin hydrogel does not result in cytotoxic effects and could be used to enhance peripheral nerve regeneration.Item Conference Report: 6th Annual International Symposium on Regenerative Rehabilitation(Future Medicine, 2018-06) Loghmani, M. Terry; Roche, Joseph A.; Physical Therapy, School of Health and Human SciencesThe 6th International Symposium on Regenerative Rehabilitation, hosted by the Alliance for Regenerative Rehabilitation Research and Training (AR3T), included a preconference meeting of institutional representatives of the International Consortium of Regenerative Rehabilitation, keynote talks from distinguished scientists, platform and poster presentations from experts and trainees, panel discussions and postconference workshops. The following priorities were identified: increasing rigor in basic, preclinical and clinical studies, especially the use of better controls; developing better outcome measures for preclinical and clinical trials; focusing on developing more tissue-based interventions versus cell-based interventions; including regenerative rehabilitation in curricula of professional programs like occupational and physical therapy; and developing better instruments to quantify rehabilitative interventions.Item Emerging targets for glioblastoma stem cell therapy(JBR, 2015-09-20) Safa, Ahmad R.; Saadatzadeh, Mohammad Reza; Cohen-Gadol, Aaron A.; Pollok, Karen E.; Bijangi-Vishehsaraei, Khadijeh; Department of Pharmacology and Toxicology, IU School of MedicineGlioblastoma multiforme (GBM), designated as World Health Organization (WHO) grade IV astrocytoma, is a lethal and therapy-resistant brain cancer comprised of several tumor cell subpopulations, including GBM stem cells (GSCs) which are believed to contribute to tumor recurrence following initial response to therapies. Emerging evidence demonstrates that GBM tumors are initiated from GSCs. The development and use of novel therapies including small molecule inhibitors of specific proteins in signaling pathways that regulate stemness, proliferation and migration of GSCs, immunotherapy, and non-coding microRNAs may provide better means of treating GBM. Identification and characterization of GSC-specific signaling pathways would be necessary to identify specific therapeutic targets which may lead to the development of more efficient therapies selectively targeting GSCs. Several signaling pathways including mTOR, AKT, maternal embryonic leucine zipper kinase (MELK), NOTCH1 and Wnt/β-catenin as well as expression of cancer stem cell markers CD133, CD44, Oct4, Sox2, Nanog, and ALDH1A1 maintain GSC properties. Moreover, the data published in the Cancer Genome Atlas (TCGA) specifically demonstrated the activated PI3K/AKT/mTOR pathway in GBM tumorigenesis. Studying such pathways may help to understand GSC biology and lead to the development of potential therapeutic interventions to render them more sensitive to chemotherapy and radiation therapy. Furthemore, recent demonstration of dedifferentiation of GBM cell lines into CSC-like cells prove that any successful therapeutic agent or combination of drugs for GBM therapy must eliminate not only GSCs, but the differentiated GBM cells and the entire bulk of tumor cells.Item The first wave of B lymphopoiesis develops independently of stem cells in the murine embryo(Wiley, 2015-02-01) Yoshimoto, Momoko; Department of Pediatrics, IU School of MedicineIn the developing mouse embryo, there are several waves of hematopoiesis. Primitive and definitive erythromyeloid lineages appear prior to hematopoietic stem cell (HSC) emergence, and these waves are considered to be transient and support embryonic homeostasis until HSC-derived hematopoiesis is established. However, recent evidence strongly suggests that HSC-independent immune cells, such as tissue macrophages and some innate lymphoid cells, develop in the mouse embryo and persist into postnatal life. Innate type B-1 cells have also been reported to emerge from hemogenic endothelial cells in the extraembryonic yolk sac and para-aortic splanchnopleura, and continue to develop in the fetal liver, even in HSC-deficient mouse embryos. Here, this review discusses B-1 cell development in the context of the layered immune system hypothesis of B lymphopoiesis and the emergence of B-1 cells independent of HSCs.Item Functional development of mechanosensitive hair cells in stem cell-derived organoids parallels native vestibular hair cells(Nature Publishing Group, 2016-05-24) Liu, Xiao-Ping; Koehler, Karl R.; Mikosz, Andrew M.; Hashino, Eri; Holt, Jeffrey R.; Department of Otolaryngology—Head & Neck Surgery, IU School of MedicineInner ear sensory epithelia contain mechanosensitive hair cells that transmit information to the brain through innervation with bipolar neurons. Mammalian hair cells do not regenerate and are limited in number. Here we investigate the potential to generate mechanosensitive hair cells from mouse embryonic stem cells in a three-dimensional (3D) culture system. The system faithfully recapitulates mouse inner ear induction followed by self-guided development into organoids that morphologically resemble inner ear vestibular organs. We find that organoid hair cells acquire mechanosensitivity equivalent to functionally mature hair cells in postnatal mice. The organoid hair cells also progress through a similar dynamic developmental pattern of ion channel expression, reminiscent of two subtypes of native vestibular hair cells. We conclude that our 3D culture system can generate large numbers of fully functional sensory cells which could be used to investigate mechanisms of inner ear development and disease as well as regenerative mechanisms for inner ear repair.
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