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Bone marrow models for heightened recruitment of Hematopoietic Stem Cells
For bone marrow transplants, large numbers of hematopoietic stem cells (HSCs) are needed. However, the in vitro expansion of HSCs remains a major challenge. So, an attractive solution is the development of 3D scaffolds that can recreate the bone marrow niche, where HSCs can be cultured and expanded.
Bone marrow transplants are the only available therapy for many cancers involving blood cells, such as leukemia or lymphoma. A major limitation of this treatment is the availability of hematopoietic stem cells (HSCs). The in vitro expansion of HSCs remains a major challenge in medicine today. HSCs grown in vitro rapidly lose their regenerative capacity likely due to the lack of niche-derived signals, comprising structural, molecular and cellular components. We are developing novel 3-dimensional scaffolds based on biomaterials that can recreate the structure of the bone marrow niche, where HSCs can be hosted. Engineering these biomaterials is key to regulate and direct HSC proliferation vs differentiation balance. Based on in vitro evaluations, best conditions to enhance HSC proliferation while maintaining their potential will be selected for in vivo test. These structures will then be implanted in mice. In vivo this engineered construct will remodel into a bone marrow-like structure. Following transplantation these ossicles will be thorough analysed for bone formation and cell recruitment by histology and FACS among others.
Bone marrow transplants are the only available therapy for many cancers involving blood cells, such as leukemia or lymphoma. A major limitation of this treatment is the availability of hematopoietic stem cells (HSCs). The in vitro expansion of HSCs remains a major challenge in medicine today. HSCs grown in vitro rapidly lose their regenerative capacity likely due to the lack of niche-derived signals, comprising structural, molecular and cellular components. We are developing novel 3-dimensional scaffolds based on biomaterials that can recreate the structure of the bone marrow niche, where HSCs can be hosted. Engineering these biomaterials is key to regulate and direct HSC proliferation vs differentiation balance. Based on in vitro evaluations, best conditions to enhance HSC proliferation while maintaining their potential will be selected for in vivo test. These structures will then be implanted in mice. In vivo this engineered construct will remodel into a bone marrow-like structure. Following transplantation these ossicles will be thorough analysed for bone formation and cell recruitment by histology and FACS among others.
To study 3D environments that highly mimic the properties of the bone marrow niche and permit the expansion of human hematopoietic stem cells
To study 3D environments that highly mimic the properties of the bone marrow niche and permit the expansion of human hematopoietic stem cells