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Li, Aileen

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Li

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Aileen

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Li, Aileen

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Now showing 1 - 4 of 4
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    Publication
    Injectable, spontaneously assembling inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy
    (2015) Kim, Jaeyun; Li, Aileen; Choi, Youngjin; Lewin, Sarah A.; Verbeke, Catia; Dranoff, Glenn; Mooney, David
    Materials implanted in the body to program host immune cells are a promising alternative to transplantation of ex vivo–manipulated cells to direct an immune response, but required a surgical procedure. Here we demonstrate that high-aspectratio, mesoporous silica rods (MSRs) injected with a needle spontaneously assemble in vivo to form macroporous structures that provide a 3D cellular microenvironment for host immune cells. In mice, substantial numbers of DCs are recruited to the pores between the scaffold rods. The recruitment of DCs and their subsequent homing to lymph nodes can be modulated by sustained release of inflammatory signals and adjuvants from the scaffold. Moreover, injection of an MSR-based vaccine formulation enhances systemic TH1 and TH2 serum antibody and cytotoxic T cell levels compared to bolus controls. These findings suggest that injectable MSRs may serve as a multifunctional vaccine platform to modulate host immune cell function and provoke adaptive immune responses.
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    Effect of Pore Structure of Macroporous Poly(Lactide-co-Glycolide) Scaffolds on the in Vivo Enrichment of Dendritic Cells
    (American Chemical Society, 2014) Kim, Jaeyun; Li, Aileen; Sands, Warren; Mooney, David
    The in vivo enrichment of dendritic cells (DCs) in implanted macroporous scaffolds is an emerging strategy to modulate the adaptive immune system. The pore architecture is potentially one of the key factors in controlling enrichment of DCs. However, there have been few studies examining the effects of scaffold pore structure on in vivo DC enrichment. Here we present the effects of surface porosity, pore size, and pore volume of macroporous poly(lactide-co-glycolide) (PLG) scaffolds encapsulating granulocyte macrophage colony-stimulating factor (GM-CSF), an inflammatory chemoattractant, on the in vivo enrichment of DCs. Although in vitro cell seeding studies using PLG scaffolds without GM-CSF showed higher cell infiltration in scaffolds with higher surface porosity, in vivo results revealed higher DC enrichment in GM-CSF loaded PLG scaffolds with lower surface porosity despite a similar level of GM-CSF released. The diminished compressive modulus of high surface porosity scaffolds compared to low surface porosity scaffolds lead to the significant shrinkage of these scaffolds in vivo, suggesting that the mechanical strength of scaffolds was critical to maintain a porous structure in vivo for accumulating DCs. The pore volume was also found to be important in total number of recruited cells and DCs in vivo. Varying the pore size significantly impacted the total number of cells, but similar numbers of DCs were found as long as the pore size was above 10–32 μm. Collectively, these results suggested that one can modulate in vivo enrichment of DCs by altering the pore architecture and mechanical properties of PLG scaffolds.
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    Deterministic encapsulation of single cells in thin tunable microgels for niche modeling and therapeutic delivery
    (2016) Mao, Angelo; Shin, Jae-Won; Utech, Stefanie; Wang, Huanan; Uzun, Oktay; Li, Aileen; Cooper, Madeline; Hu, Yuebi; Zhang, Liyuan; Weitz, David; Mooney, David
    Existing techniques to encapsulate cells into microscale hydrogels generally yield high polymer-to-cell ratios and lack control over the hydrogel’s mechanical properties1. Here, we report a microfluidic-based method for encapsulating single cells in a ~6 micron layer of alginate that increases the proportion of cell-containing microgels by 10-fold, with encapsulation efficiencies over 90%. We show that in vitro cell viability was maintained over a three-day period, that the microgels are mechanically tractable, and that for microscale cell assemblages of encapsulated marrow stromal cells cultured in microwells, osteogenic differentiation of encapsulated cells depends on gel stiffness and cell density. We also show that intravenous injection of singly-encapsulated marrow stromal cells into mice delays clearance kinetics and sustains donor-derived soluble factors in vivo. The encapsulation of single cells in tunable hydrogels should find use in a variety of tissue engineering and regenerative medicine applications.
  • Publication
    Treating ischemia via recruitment of antigen-specific T cells
    (American Association for the Advancement of Science (AAAS), 2019-07) Kwee, Brian; Seo, Bo Ri; Najibi, Alexander; Li, Aileen; Shih, Ting-Yu; White, Des; Mooney, David
    Ischemic diseases are a leading cause of mortality and can result in autoamputation of lower limbs. We explored the hypothesis that implantation of an antigen-releasing scaffold, in animals previously vaccinated with the same antigen, can concentrate TH2 T cells and enhance vascularization of ischemic tissue. This approach may be clinically relevant, as all persons receiving childhood vaccines recommended by the Centers for Disease Control and Prevention have vaccines that contain aluminum, a TH2 adjuvant. To test the hypothesis, mice with hindlimb ischemia, previously vaccinated with ovalbumin (OVA) and aluminum, received OVA-releasing scaffolds. Vaccinated mice receiving OVA-releasing scaffolds locally concentrated antigen-specific TH2 T cells in the surrounding ischemic tissue. This resulted in local angiogenesis, increased perfusion in ischemic limbs, and reduced necrosis and enhanced regenerating myofibers in the muscle. These findings support the premise that antigen depots may provide a treatment for ischemic diseases in patients previously vaccinated with aluminum-containing adjuvants.