{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/115673"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/115673","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Developing a biomaterial model of the bone marrow perivascular niche for the study of hematopoietic stem cells","abstract":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-05-01","abstract_html":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-05-01","abstract_has_math":false,"creators":["Barnhouse, Victoria Rae"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Bioengineering","degree_department":null,"school":null,"contributors":["Harley , Brendan AC","Boppart, Marni","Underhill, Gregory","Cunningham , Brian"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-05","date_published":"2022-05","updated_at":"2026-07-22T22:24:54Z","subjects":["hematopoietic stem cells","perivascular niche","biomaterials","hypoxia"],"languages":["en","eng"],"rights":["Copyright 2022 Victoria Barnhouse"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/115673","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Harley , Brendan AC","Boppart, Marni","Underhill, Gregory","Cunningham , Brian"]},{"key":"dc:creator","label":"Author","values":["Barnhouse, Victoria Rae"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-05","2022-03-31"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Bioengineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["hematopoietic stem cells","perivascular niche","biomaterials","hypoxia"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2022 Victoria Barnhouse"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/115673"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-05-01","The student, Victoria Barnhouse, accepted the attached license on 2022-03-28 at 13:59.","The student, Victoria Barnhouse, submitted this Dissertation for approval on 2022-03-28 at 14:40.","This Dissertation was approved for publication on 2022-03-31 at 15:19.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17549 on 2022-11-11 at 12:18:46","Hematopoietic stem cells (HSCs) are responsible for producing the body’s full complement of blood and immune cells through the process of hematopoiesis. These rare cells (0.007% of the bone marrow) can self-renew and differentiate to produce multiple cell lines. HSCs primarily reside in the bone marrow in specific microenvironments termed niches. The niche environment provides biophysical, cellular, and biochemical cues to guide HSC fate decisions such as proliferation, mobilization, self-renewal, and differentiation. HSCs are used clinically as a curative therapy for malignancies and disorders of the blood and immune system, such as leukemia and lymphoma. However, these transplants still have a high rate of failure, typically due to relapse of the primary disease but can also be caused by issues related to transplants, including low stem cell dose, failure to engraft, and graft vs host disease. Transplant success is correlated with the number of cells infused, thus methods to expand HSCs prior to transplant are under investigation. A better understanding of the native HSC niche will aid in the development of ex vivo expansion methods. One niche known to be important for retention of primitive HSCs is the perivascular niche, the region existing within ~20μm of blood vessels within the marrow. In this work, we describe the development of a tissue engineering model of the bone marrow perivascular niche to provide cellular, biophysical, and biochemical cues to HSCs. We first investigate the ability for angiocrine signals from the perivascular niche to maintain primitive HSPCs. We then report a microfluidic approach to create vascular gradients then investigate dose-dependent effects of vascular network density on Akt vs. MAPK signaling as well as Notch signaling through Jagged-1. We then describe a murine bone marrow-derived perivascular niche model, characterizing metrics of network formation, basement membrane deposition, and secretome to consider the arteriolar vs sinusoidal nature of the model. Direct co-culture of perivascular cells and HSCs is then examined for the potential to support expansion of differentiated hematopoietic cells while also maintaining a subpopulation of HSCs. Finally, we investigate the role of hypoxia on murine bone marrow perivascular network formation as well as subsequent proliferation versus maintenance of HSCs. Together, this thesis describes a series of new engineered microphysiological models to provide insight into how the bone marrow perivascular environment may influence HSC fate decisions."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Developing a biomaterial model of the bone marrow perivascular niche for the study of hematopoietic stem cells"]}]}],"canonical_facts":{"dc:contributor":["Harley , Brendan AC","Boppart, Marni","Underhill, Gregory","Cunningham , Brian"],"dc:creator":["Barnhouse, Victoria Rae"],"dc:date":["2022-05","2022-03-31"],"dc:description":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-05-01","The student, Victoria Barnhouse, accepted the attached license on 2022-03-28 at 13:59.","The student, Victoria Barnhouse, submitted this Dissertation for approval on 2022-03-28 at 14:40.","This Dissertation was approved for publication on 2022-03-31 at 15:19.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17549 on 2022-11-11 at 12:18:46","Hematopoietic stem cells (HSCs) are responsible for producing the body’s full complement of blood and immune cells through the process of hematopoiesis. These rare cells (0.007% of the bone marrow) can self-renew and differentiate to produce multiple cell lines. HSCs primarily reside in the bone marrow in specific microenvironments termed niches. The niche environment provides biophysical, cellular, and biochemical cues to guide HSC fate decisions such as proliferation, mobilization, self-renewal, and differentiation. HSCs are used clinically as a curative therapy for malignancies and disorders of the blood and immune system, such as leukemia and lymphoma. However, these transplants still have a high rate of failure, typically due to relapse of the primary disease but can also be caused by issues related to transplants, including low stem cell dose, failure to engraft, and graft vs host disease. Transplant success is correlated with the number of cells infused, thus methods to expand HSCs prior to transplant are under investigation. A better understanding of the native HSC niche will aid in the development of ex vivo expansion methods. One niche known to be important for retention of primitive HSCs is the perivascular niche, the region existing within ~20μm of blood vessels within the marrow. In this work, we describe the development of a tissue engineering model of the bone marrow perivascular niche to provide cellular, biophysical, and biochemical cues to HSCs. We first investigate the ability for angiocrine signals from the perivascular niche to maintain primitive HSPCs. We then report a microfluidic approach to create vascular gradients then investigate dose-dependent effects of vascular network density on Akt vs. MAPK signaling as well as Notch signaling through Jagged-1. We then describe a murine bone marrow-derived perivascular niche model, characterizing metrics of network formation, basement membrane deposition, and secretome to consider the arteriolar vs sinusoidal nature of the model. Direct co-culture of perivascular cells and HSCs is then examined for the potential to support expansion of differentiated hematopoietic cells while also maintaining a subpopulation of HSCs. Finally, we investigate the role of hypoxia on murine bone marrow perivascular network formation as well as subsequent proliferation versus maintenance of HSCs. Together, this thesis describes a series of new engineered microphysiological models to provide insight into how the bone marrow perivascular environment may influence HSC fate decisions."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/115673"],"dc:language":["en","eng"],"dc:rights":["Copyright 2022 Victoria Barnhouse"],"dc:subject":["hematopoietic stem cells","perivascular niche","biomaterials","hypoxia"],"dc:title":["Developing a biomaterial model of the bone marrow perivascular niche for the study of hematopoietic stem cells"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Bioengineering"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:54Z"}