Browsing by Author "Stewart, Samantha"

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    Bioinspired One Cell Culture Isolates Highly Tumorigenic and Metastatic Cancer Stem Cells Capable of Multilineage Differentiation
    (Wiley, 2020-04-28) Wang, Hai; Agarwal, Pranay; Jiang, Bin; Stewart, Samantha; Liu, Xuanyou; Liang, Yutong; Hancioglu, Baris; Webb, Amy; Fisher, John P.; Liu, Zhenguo; Lu, Xiongbin; Tkaczuk, Katherine H. R.; He, Xiaoming
    Cancer stem cells (CSCs) are rare cancer cells that are postulated to be responsible for cancer relapse and metastasis. However, CSCs are difficult to isolate and poorly understood. Here, a bioinspired approach for label-free isolation and culture of CSCs, by microencapsulating one cancer cell in the nanoliter-scale hydrogel core of each prehatching embryo-like core–shell microcapsule, is reported. Only a small percentage of the individually microencapsulated cancer cells can proliferate into a cell colony. Gene and protein expression analyses indicate high stemness of the cells in the colonies. Importantly, the colony cells are capable of cross-tissue multilineage (e.g., endothelial, cardiac, neural, and osteogenic) differentiation, which is not observed for “CSCs” isolated using other contemporary approaches. Further studies demonstrate the colony cells are highly tumorigenic, metastatic, and drug resistant. These data show the colony cells obtained with the bioinspired one-cell-culture approach are truly CSCs. Significantly, multiple pathways are identified to upregulate in the CSCs and enrichment of genes related to the pathways is correlated with significantly decreased survival of breast cancer patients. Collectively, this study may provide a valuable method for isolating and culturing CSCs, to facilitate the understanding of cancer biology and etiology and the development of effective CSC-targeted cancer therapies.
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    In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy
    (Springer Nature, 2023-01-24) Ou, Wenquan; Stewart, Samantha; White, Alisa; Kwizera, Elyahb A.; Xu, Jiangsheng; Fang, Yuanzheng; Shamul, James G.; Xie, Changqing; Nurudeen, Suliat; Tirada, Nikki P.; Lu, Xiongbin; Tkaczuk, Katherine H.R.; He, Xiaoming
    Cancer immunotherapy that deploys the host’s immune system to recognize and attack tumors, is a promising strategy for cancer treatment. However, its efficacy is greatly restricted by the immunosuppressive (i.e., immunologically cold) tumor microenvironment (TME). Here, we report an in-situ cryo-immune engineering (ICIE) strategy for turning the TME from immunologically “cold” into “hot”. In particular, after the ICIE treatment, the ratio of the CD8+ cytotoxic T cells to the immunosuppressive regulatory T cells is increased by more than 100 times in not only the primary tumors with cryosurgery but also distant tumors without freezing. This is achieved by combining cryosurgery that causes “frostbite” of tumor with cold-responsive nanoparticles that not only target tumor but also rapidly release both anticancer drug and PD-L1 silencing siRNA specifically into the cytosol upon cryosurgery. This ICIE treatment leads to potent immunogenic cell death, which promotes maturation of dendritic cells and activation of CD8+ cytotoxic T cells as well as memory T cells to kill not only primary but also distant/metastatic breast tumors in female mice (i.e., the abscopal effect). Collectively, ICIE may enable an efficient and durable way to leverage the immune system for combating cancer and its metastasis.
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    MULTISCALE TECHNOLOGIES FOR ENGINEERING AND CRYOPRESERVING OVARIAN TISSUES AND HUMAN IPSCs
    (2023) Stewart, Samantha; He, Xiaoming; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    An estimated 9.8 million reproductive-age people with ovaries in the United States are impactedby fertility issues, oftentimes caused by the dysregulation of the tightly controlled process of ovarian follicle development. Impaired fertility can arise from disorders like polycystic ovarian syndrome (PCOS) or premature ovarian insufficiency (POI), which affect the function of the ovary, an integral reproductive organ that houses the ovarian follicles. POI can also negatively impact endocrine function, decreasing estrogen and leading to increased risk of osteoporosis, cardiovascular disease, and neurological disorders. Novel fertility preservation and restoration strategies, like ovarian tissue engineering, have emerged to address these effects of ovarian dysregulation and offer alternatives for those who wish to delay childbearing. Human induced pluripotent stem cells (hiPSCs) hold tremendous potential for tissue engineering and cell-based medicine, as they have the capacity of differentiating into ectodermal, mesodermal, endodermal, and germ cell lineages. In recent years, research into differentiating hiPSCs into cells like those that make up the ovary has garnered much interest, highlighting these cells as a promising source for ovarian tissue engineering and other types of cell-based medicine and research. This work addresses critical challenges associated with engineering ovarian tissue for reproductive and cellbased medicine: (1) engineering the microenvironment for the cell/microtissue and (2) cryopreservation of the cells/microtissues. To understand the microenvironment of the ovary for informed tissue engineering system design, we spatially characterize the micromechanical properties of ovarian tissue from domestic cats to reveal both elastic and viscoelastic property heterogeneities, correlating these findings with the distribution of key extracellular matrix (ECM) molecules. We then developed a novel cryopreservation technology to enhance cryopreservation of ovarian follicles and hiPSCs, using sand to seed ice in the extracellular solution at high subzero temperatures during cooling. Together, this work investigates multiscale strategies for advancing ovarian tissue engineering, contributing to the advancement of reproductive medicine approaches for treating infertility and related endocrine dysfunction.