{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/110616"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/110616","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Soluble factors and remodeling in a synthetic stem cell niche","abstract":"Hematopoietic stem cells produce the body’s entire complement of blood and immune cells, in a process known as hematopoiesis. Producing half a trillion cells daily, this rare population (<0.01% of human bone marrow) possess the ability to produce multiple cell lines (differentiation) and stem cell daughters (self-renewal). HSCs are found throughout the body but primarily reside in the adult bone marrow, in specialized compartments termed the niche. Within the niche is a host of biophysical, cellular, and soluble factor cues that combine in temporally and spatially organized zones which elicit distinct responses from resident HSCs. Clinically, HSC transplants are the most widely used regenerative therapy, treating disorders of the blood and immune system e.g., anemias, leukemias, and myelo-ablative chemoradiation treatments. However, the rarity of the cells and scarcity of appropriately matched donors (<25% in some demographics) has necessitated methods to expand and maintain HSC populations ex vivo. Development of expansion methods requires identification of essential features of the native HSC microenvironment for design of tissue engineering constructs. Herein, we describe the use of gelatin-based hydrogels to provide biophysical cues, recapitulating mechanical features of the niche. Cellular cues are provided by heterotypic cultures of niche-associated mesenchymal stromal cells (MSCs) and HSCs. The cell-cell interactions are mediated by biotransport of secreted soluble factors, which are in turn mediated by the biophysical properties of the matrix. This interdependence motivates a series of investigations to define the role of material properties on transport-mediated cell-cell interactions as well as the role of cell-mediated remodeling on dynamic cell interactions. We identified a regime of HSC-MSC interactions that improve maintenance of HSCs in an environment with restricted biotransport. Employing mathematical modeling techniques, features of the artificial niche (soluble factors) were correlated to hematopoietic activity. To adapt conventional macro-scale hydrogel platforms to study HSC activity at single cell resolution, this thesis also describes development of micro-scale (~150 µm) droplet hydrogels with control over cell-cell interactions and enables high-throughput generation of identical microenvironments. Overall, these studies demonstrate that dynamic cell-cell signaling are essential features in artificial niche for ex vivo HSC culture and expansion.","abstract_html":"Hematopoietic stem cells produce the body’s entire complement of blood and immune cells, in a process known as hematopoiesis. Producing half a trillion cells daily, this rare population (&lt;0.01% of human bone marrow) possess the ability to produce multiple cell lines (differentiation) and stem cell daughters (self-renewal). HSCs are found throughout the body but primarily reside in the adult bone marrow, in specialized compartments termed the niche. Within the niche is a host of biophysical, cellular, and soluble factor cues that combine in temporally and spatially organized zones which elicit distinct responses from resident HSCs. Clinically, HSC transplants are the most widely used regenerative therapy, treating disorders of the blood and immune system e.g., anemias, leukemias, and myelo-ablative chemoradiation treatments. However, the rarity of the cells and scarcity of appropriately matched donors (&lt;25% in some demographics) has necessitated methods to expand and maintain HSC populations ex vivo. Development of expansion methods requires identification of essential features of the native HSC microenvironment for design of tissue engineering constructs. Herein, we describe the use of gelatin-based hydrogels to provide biophysical cues, recapitulating mechanical features of the niche. Cellular cues are provided by heterotypic cultures of niche-associated mesenchymal stromal cells (MSCs) and HSCs. The cell-cell interactions are mediated by biotransport of secreted soluble factors, which are in turn mediated by the biophysical properties of the matrix. This interdependence motivates a series of investigations to define the role of material properties on transport-mediated cell-cell interactions as well as the role of cell-mediated remodeling on dynamic cell interactions. We identified a regime of HSC-MSC interactions that improve maintenance of HSCs in an environment with restricted biotransport. Employing mathematical modeling techniques, features of the artificial niche (soluble factors) were correlated to hematopoietic activity. To adapt conventional macro-scale hydrogel platforms to study HSC activity at single cell resolution, this thesis also describes development of micro-scale (~150 µm) droplet hydrogels with control over cell-cell interactions and enables high-throughput generation of identical microenvironments. Overall, these studies demonstrate that dynamic cell-cell signaling are essential features in artificial niche for ex vivo HSC culture and expansion.","abstract_has_math":false,"creators":["Gilchrist, Aidan E"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Materials Science & Engr","degree_department":null,"school":null,"contributors":["Harley, Brendan","Das Neves Barbosa Leal Lauten, Cecelia","Sottos, Nancy","Cheng, JianJun"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-09-17T02:34:09Z","date_published":"2021-09-17T02:34:09Z","updated_at":"2026-07-22T22:24:52Z","subjects":["biomaterials","hematopoietic stem cells","stem cell engineering"],"languages":["en"],"rights":["Copyright 2020 Aidan Gilchrist"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/110616","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Harley, Brendan","Das Neves Barbosa Leal Lauten, Cecelia","Sottos, Nancy","Cheng, JianJun"]},{"key":"dc:creator","label":"Author","values":["Gilchrist, Aidan E"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2021-09-17T02:34:09Z","2023-09-17T02:34:57Z","2020-12-15","2021-05"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Materials Science & Engr"]},{"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":["biomaterials","hematopoietic stem cells","stem cell engineering"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2020 Aidan Gilchrist"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/110616"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Hematopoietic stem cells produce the body’s entire complement of blood and immune cells, in a process known as hematopoiesis. Producing half a trillion cells daily, this rare population (<0.01% of human bone marrow) possess the ability to produce multiple cell lines (differentiation) and stem cell daughters (self-renewal). HSCs are found throughout the body but primarily reside in the adult bone marrow, in specialized compartments termed the niche. Within the niche is a host of biophysical, cellular, and soluble factor cues that combine in temporally and spatially organized zones which elicit distinct responses from resident HSCs. Clinically, HSC transplants are the most widely used regenerative therapy, treating disorders of the blood and immune system e.g., anemias, leukemias, and myelo-ablative chemoradiation treatments. However, the rarity of the cells and scarcity of appropriately matched donors (<25% in some demographics) has necessitated methods to expand and maintain HSC populations ex vivo. Development of expansion methods requires identification of essential features of the native HSC microenvironment for design of tissue engineering constructs. Herein, we describe the use of gelatin-based hydrogels to provide biophysical cues, recapitulating mechanical features of the niche. Cellular cues are provided by heterotypic cultures of niche-associated mesenchymal stromal cells (MSCs) and HSCs. The cell-cell interactions are mediated by biotransport of secreted soluble factors, which are in turn mediated by the biophysical properties of the matrix. This interdependence motivates a series of investigations to define the role of material properties on transport-mediated cell-cell interactions as well as the role of cell-mediated remodeling on dynamic cell interactions. We identified a regime of HSC-MSC interactions that improve maintenance of HSCs in an environment with restricted biotransport. Employing mathematical modeling techniques, features of the artificial niche (soluble factors) were correlated to hematopoietic activity. To adapt conventional macro-scale hydrogel platforms to study HSC activity at single cell resolution, this thesis also describes development of micro-scale (~150 µm) droplet hydrogels with control over cell-cell interactions and enables high-throughput generation of identical microenvironments. Overall, these studies demonstrate that dynamic cell-cell signaling are essential features in artificial niche for ex vivo HSC culture and expansion.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-05-01","The student, Aidan Gilchrist, accepted the attached license on 2020-12-05 at 11:43.","The student, Aidan Gilchrist, submitted this Dissertation for approval on 2020-12-05 at 11:49.","This Dissertation was approved for publication on 2020-12-15 at 14:07.","DSpace SAF Submission Ingestion Package generated from Vireo submission #16078 on 2021-09-16 at 17:01:27","Made available in DSpace on 2021-09-17T02:34:09Z (GMT). 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Producing half a trillion cells daily, this rare population (<0.01% of human bone marrow) possess the ability to produce multiple cell lines (differentiation) and stem cell daughters (self-renewal). HSCs are found throughout the body but primarily reside in the adult bone marrow, in specialized compartments termed the niche. Within the niche is a host of biophysical, cellular, and soluble factor cues that combine in temporally and spatially organized zones which elicit distinct responses from resident HSCs. Clinically, HSC transplants are the most widely used regenerative therapy, treating disorders of the blood and immune system e.g., anemias, leukemias, and myelo-ablative chemoradiation treatments. However, the rarity of the cells and scarcity of appropriately matched donors (<25% in some demographics) has necessitated methods to expand and maintain HSC populations ex vivo. Development of expansion methods requires identification of essential features of the native HSC microenvironment for design of tissue engineering constructs. Herein, we describe the use of gelatin-based hydrogels to provide biophysical cues, recapitulating mechanical features of the niche. Cellular cues are provided by heterotypic cultures of niche-associated mesenchymal stromal cells (MSCs) and HSCs. The cell-cell interactions are mediated by biotransport of secreted soluble factors, which are in turn mediated by the biophysical properties of the matrix. This interdependence motivates a series of investigations to define the role of material properties on transport-mediated cell-cell interactions as well as the role of cell-mediated remodeling on dynamic cell interactions. We identified a regime of HSC-MSC interactions that improve maintenance of HSCs in an environment with restricted biotransport. Employing mathematical modeling techniques, features of the artificial niche (soluble factors) were correlated to hematopoietic activity. To adapt conventional macro-scale hydrogel platforms to study HSC activity at single cell resolution, this thesis also describes development of micro-scale (~150 µm) droplet hydrogels with control over cell-cell interactions and enables high-throughput generation of identical microenvironments. Overall, these studies demonstrate that dynamic cell-cell signaling are essential features in artificial niche for ex vivo HSC culture and expansion.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-05-01","The student, Aidan Gilchrist, accepted the attached license on 2020-12-05 at 11:43.","The student, Aidan Gilchrist, submitted this Dissertation for approval on 2020-12-05 at 11:49.","This Dissertation was approved for publication on 2020-12-15 at 14:07.","DSpace SAF Submission Ingestion Package generated from Vireo submission #16078 on 2021-09-16 at 17:01:27","Made available in DSpace on 2021-09-17T02:34:09Z (GMT). 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