Microtube Array Membrane (MTAM)-Based Encapsulated Cell Therapy for Cancer Treatment

Abstract

The treatment of cancer has evolved significantly in recent years with a strong focus on immunotherapy. Encapsulated Cell Therapy (ECT) for immunotherapy-based anti-cancer treatment is a unique niche within this landscape, where molecules such as signaling factors and antibodies produced from cells are encapsulated within a vehicle, with a host amount of benefits in terms of treatment efficacy and reduced side effects. However, traditional ECTs generally lie in two extremes; either a macro scale vehicle is utilized, resulting in a retrievable system but with limited diffusion and surface area, or a micro scale vehicle is utilized, resulting in a system that has excellent diffusion and surface area but is unretrievable in the event of side effects occurring, which greatly compromises the biosafety of patients. In this study we adapted our patented and novel electrospun Polysulfone (PSF) Microtube Array Membranes (MTAMs) as a ‘middle’ approach to the above dilemma, which possess excellent diffusion and surface area while being retrievable. Hybridoma cells were encapsulated within the PSF MTAMs, where they produced CEACAM6 antibodies to be used in the suppression of cancer cell line A549, MDA-MB-468 and PC 3 (control). In vitro and in vivo studies revealed excellent cell viability of hybridoma cells with continuous secretion of CEACAM6 antibodies which suppressed the MDA-MB-468 throughout the entire 21 days of experiment. Such outcome suggested that the PSF MTAMs were not only an excellent three-dimensional (3D) cell culture substrate but potentially also an excellent vehicle for the application in ECT systems. Future research needs to include a long term in vivo >6 months study before it can be used in clinical applications.

Tissue-Engineered Vascular Graft with Co-Culture of Smooth Muscle Cells and Human Endothelial Vein Cells on an Electrospun Poly(lactic-co-glycolic acid) Microtube Array Membrane

“…PLGA MTAMs, which consisted of one-to-one connected individual ultra-thin fibers arranged in an arrayed formation, were successfully fabricated. Compared to the MTAMs of Polylactic Acid (PLLA) and Polysulfone (PSF) in our previous work, the fibers here appeared to be squared in shape, as opposed to those in our previous works [45][46][47]. The lumen walls of the PLGA MTAMs, which consisted of a homogenously porous pore with a narrow distribution of between 32-36 nm (Figure 2), suggested an excellent ability to precisely control the pore sizes through our internally developed porogen-surfactant ratio.…”

Microtube Array Membrane Encapsulated Cell Therapy: A Novel Platform Technology Solution for Treatment of Alzheimer’s Disease

“…In light of these difficulties, we are working to implement a new type of hollow fibers that we invented internally dubbed Microtube Array Membrane (MTAM) [ 21 ]. MTAMs are made up of one-to-one coupled ultra-thin microtube fibers that are organized in an array [ 22 , 23 , 24 ]. The lumen walls of MTAMs are 100 times thinner (2–3 micron) than those of standard hollow fibers (HFs) as compared to traditional HFs.…”

Ultra-High Packing Density Next Generation Microtube Array Membrane for Absorption Based Applications

“…Microstructurally, the MTAMs consist of one-to-one connected ultra-thin, individually connected hollow fibers that are arranged in an arrayed formation and with superior surface area for diffusion/absorption [ 36 , 37 ]. The unique microstructure translated to an excellent packing density, short perfusion distance, ease of handling on a macro scale, which allowed this platform technology to be applied in multiple areas ranging from anticancer drug screening [ 38 ], endotoxin removal [ 1 ], tissue regeneration [ 39 , 40 , 41 ], microbial fuel cell [ 42 ], encapsulated cell therapy [ 43 ], and fermentation [ 44 , 45 , 46 ]. To further improve on the capability of MTAMs, we successfully developed the next generation MTAMs known as MTAM-Alternating (MTAM-A), which has a superior surface area of up to 2.3–2.5 times when compared to traditional MTAMs [ 1 ].…”