A. James Clark School of Engineering

Permanent URI for this communityhttp://hdl.handle.net/1903/1654

The collections in this community comprise faculty research works, as well as graduate theses and dissertations.

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Author: search.filters.author.Fisher, John P.

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    Mesenchymal Stem Cell Culture within Perfusion Bioreactors Incorporating 3D-Printed Scaffolds Enables Improved Extracellular Vesicle Yield with Preserved Bioactivity
    (Wiley, 2023-03-17) Kronstadt, Stephanie M.; Patel, Divya B.; Born, Louis J.; Levy, Daniel; Lerman, Max J.; Mahadik, Bhushan; McLoughlin, Shannon T.; Fasuyi, Arafat; Fowlkes, Lauren; Van Heyningen, Lauren Hoorens; Aranda, Amaya; Abadchi, Sanaz Nourmohammadi; Chang, Kai-Hua; Hsu, Angela Ting Wei; Bengali, Sameer; Harmon, John W.; Fisher, John P.; Jay, Steven M.
    Extracellular vesicles (EVs) are implicated as promising therapeutics and drug delivery vehicles in various diseases. However, successful clinical translation will depend on the development of scalable biomanufacturing approaches, especially due to the documented low levels of intrinsic EV-associated cargo that may necessitate repeated doses to achieve clinical benefit in certain applications. Thus, here the effects of a 3D-printed scaffold-perfusion bioreactor system are assessed on the production and bioactivity of EVs secreted from bone marrow-derived mesenchymal stem cells (MSCs), a cell type widely implicated in generating EVs with therapeutic potential. The results indicate that perfusion bioreactor culture induces an ≈40-80-fold increase (depending on measurement method) in MSC EV production compared to conventional cell culture. Additionally, MSC EVs generated using the perfusion bioreactor system significantly improve wound healing in a diabetic mouse model, with increased CD31+ staining in wound bed tissue compared to animals treated with flask cell culture-generated MSC EVs. Overall, this study establishes a promising solution to a major EV translational bottleneck, with the capacity for tunability for specific applications and general improvement alongside advancements in 3D-printing technologies.
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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.