The human bone marrow (BM) is one of the most complex and critical tissues in the adult, functioning as the site for blood and immune cell production in homeostasis, injury, and disease. The marrow acts as an incredibly diverse stem cell niche, containing stromal and blood cells that help support the maintenance and differentiation capacity of hematopoietic stem and progenitor cells (HSPCs). The cell-cell and cell-matrix interactions within the niche help alter the marrow to trigger blood cell production in response to injury, as well as harbor downstream changes that may persist in the hematopoietic system during disease, such as in cancer metastasis or leukemias of the BM.
As the development of engineered human tissue models including organs-on-a-chip (OoC) have emerged over the past decade, there has been an increased relevance of using human BM models to study human- and patient-specific immune interactions in vitro. In this dissertation, we have developed patient-specific bioengineering technologies to model the BM, as well as those to study multi-organ interactions, for a host of translational applications of injury and disease.
In Chapters 1 and 2, we introduce a number of concepts in bioengineering and stem cell biology for studying human organ functions outside of the body. In Chapter 3, we describe the tools that are critical for modeling individual organ functions (healthy human BM) and immune cells, as well as when combining multiple OoC systems together. In Chapter 4, we apply these tools for disease modeling, in studying the complex interactions in either acute leukemia development or metastatic colonization of the BM. In Chapter 5, we use our human-specific engineered models for studies of acute and systemic injury, including the effects of cosmic radiation on human tissue function.
To tie together the tissue engineered tools developed in this thesis, we described in Chapter 6 the utility of scientific outreach and social media in the widespread dissemination of tissue engineering and stem cell principles to the broader scientific community and general public. Collectively, this dissertation provides a unique look at the use of engineered human tissue systems to model human blood and immune interactions using bioengineering tools, with applications in disease modeling of primary and metastatic cancers, as well as in acute and systemic injuries.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/mztm-6s83 |
| Date | January 2023 |
| Creators | Tavakol, Daniel Naveed |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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