The objectives of this research is to advance human health by evaluating interventions to minimize the detrimental effects of acute whole body gamma irradiation on bone metabolism, bone architecture and bone reconstruction using a mouse model. Total body irradiation (TBI) followed by adoptive transfer of bone marrow from donor animals is routinely performed in basic research in immunology and is becoming more common in bone biology. However, the high doses of ionizing radiation used for adoptive transfer can result in growth suppression and irreversible bone loss. Additionally, the respective role of depletion of mesenchymal and hematopoietic lineage cells in mediating radiation-induced bone loss is unclear. The goal of this research is to: 1) compare the efficacy of adoptive transfer of whole bone marrow and purified hematopoietic stem cells (HSCs) from
Green Fluorescent Protein GFP expressing donor mice; and 2) optimize treatment to minimize bone loss. Two studies were designed and carried out in order to reach these goals. In the first study, we compared untreated mice with irradiated mice transplanted with either unfractionated bone marrow or purified HSCs from GFP-labeled mice. Both methods reconstituted hematopoietic lineage cells but the irradiated mice experienced significant bone loss. We hypothesize that the efficacy of purified HSCs with conventional bone marrow transplantation demonstrates the method can be used for lineage tracing studies. From this result, we attempt to optimize radiation treatment by dose fractionation to minimize bone loss. The negative effects of irradiation on the skeleton are hypothesized to be reduced using fractionated irradiation. In the second study we performed adoptive transfer of purified HSCs following fractionated γ-irradiation. Two months later, bone response was evaluated by dual energy X-ray absorptiometry, micro-computed tomography, histomorphometry. Few differences were detected between the irradiated and untreated mice indicating the potential to perform adoptive transfer with purified HSCs with minimal collateral damage to bone. These findings demonstrate the potential for replacing host hematopoietic stem cells with donor stem cells with minimal collateral damage to bone. This finding is significant because it may be possible to use this method as a research tool for investigating cell based therapies to treat hematological diseases.
description.provenance : Submitted by Richard Deyhle Jr (firstname.lastname@example.org) on 2017-10-03T20:34:02ZNo. of bitstreams: 1DeyhleRichardT2017.pdf: 1756463 bytes, checksum: 6d1d1f20c19ee3bb4003064d22b6abb7 (MD5)
description.provenance : Approved for entry into archive by Julie Kurtz(email@example.com) on 2017-10-11T15:27:06Z (GMT) No. of bitstreams: 1RichardDeyhleT2017.pdf: 1764746 bytes, checksum: ff7ff4a75cc0fcb7cfcb2e905e091d49 (MD5)
description.provenance : Submitted by Richard Deyhle Jr (firstname.lastname@example.org) on 2017-10-10T19:58:34ZNo. of bitstreams: 1RichardDeyhleT2017.pdf: 1764746 bytes, checksum: ff7ff4a75cc0fcb7cfcb2e905e091d49 (MD5)
description.provenance : Rejected by Julie Kurtz(email@example.com), reason: Hi Richard,Rejecting because none of the changes were made to the pretext pages. I emailed you a copy of the pages to make revisions to. Once done, log back into ScholarsArchive and go to the upload page. Replace the attached file with the revised PDF and resubmit.Thanks,Julie on 2017-10-04T18:14:04Z (GMT)
description.provenance : Made available in DSpace on 2017-12-05T19:58:18Z (GMT). No. of bitstreams: 1RichardDeyhleT2017.pdf: 1764746 bytes, checksum: ff7ff4a75cc0fcb7cfcb2e905e091d49 (MD5)
description.provenance : Approved for entry into archive by Steven Van Tuyl(firstname.lastname@example.org) on 2017-12-05T19:58:18Z (GMT) No. of bitstreams: 1RichardDeyhleT2017.pdf: 1764746 bytes, checksum: ff7ff4a75cc0fcb7cfcb2e905e091d49 (MD5)