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

Abstract

Alzheimer’s disease is the most frequent form of dementia in aging population and is presently the world’s sixth largest cause of mortality. With the advancement of therapies, several solutions have been developed such as passive immunotherapy against these misfolded proteins, thereby resulting in the clearance. Within this segment, encapsulated cell therapy (ECT) solutions that utilize antibody releasing cells have been proposed with a multitude of techniques under development. Hence, in this study, we utilized our novel and patented Microtube Array Membranes (MTAMs) as an encapsulating platform system with anti-pTau antibody-secreting hybridoma cells to study the impact of it on Alzheimer’s disease. In vivo results revealed that in the water maze, the mice implanted with hybridoma cell MTAMs intracranially (IN) and subcutaneously (SC) showed improvement in the time spent the goal quadrant and escape latency. In passive avoidance, hybridoma cell loaded MTAMs (IN and SC) performed significantly well in step-through latency. At the end of treatment, animals with hybridoma cell loaded MTAMs had lower phosphorylated tau (pTau) expression than empty MTAMs had. Combining both experimental results unveiled that the clearance of phosphorylated tau might rescue the cognitive impairment associated with AD.

Review of electrospun microtube array membrane (MTAM)‐a novel new class of hollow fiber for encapsulated cell therapy (ECT) in clinical applications

“…12,26 Additionally, the encapsulated cells not only maintained functional viability but also showed a noticeable growth tendency before plateauing and maintaining overall vitality throughout the period of our earlier demonstration examples. 12,26,36 Most intriguingly, direct injection of high-density stem cells tends to be undetectable as early as 24 hours after injection and as late as 14 days, depending on the injection location. 37 However, therapeutic elements like exosomes were continuously secreted when the stem cells were encapsulated within our MTAMs, and considerable therapeutic benefits were seen as well, as will be covered in the cardiac patch in the next sections.…”

“…Critically, as demonstrated above, the therapeutic protein did indeed travel from the implant site to the target disease site via the vascular system and successfully registered an improvement to both the behavioral and memory test of the mouse model. 26 These findings were further supported when Western Blot assay of the pTau protein in various regions of the mouse model brain registered significantly lower levels when implanted with the hybridoma loaded PSF MTAMs.…”

“…30 Additionally, hybridoma cells were effectively maintained for up to 30 days for the treatment of triple negative breast cancer cell lines in situations where encapsulated cell treatments proof of concept that were presented, and for up to 45 days for the treatment of Alzhimer's disease. 12,26 The most surprising result was that, when compared to hybridoma cells grown on standard tissue culture plates (TCPs), those grown in MTAM encapsulation demonstrated a significantly greater functional viability, with therapeutic antibodies continually produced at a higher level and for a longer length of time. These antibodies were able to travel to the distal region of the animal model for therapy of the illnesses as described above by diffusing unrestricted over the lumen wall into the surrounding blood stream.…”

“…enclosed within the MTAMs were in no way harmed by the retention of these "detrimental exosomes" in terms of long-term functional viability, as demonstrated in several of our previous work. 12,26 Given that the separation and recovery of exosomes using the currently available approach has been expensive, time-consuming, and has a very poor yield, we anticipate that this capability will be of utmost importance in future exosome related applications. [27][28][29] Another key aspect of the uniqueness of the MTAM as a platform solution for encapsulated cell therapy lies in the ultra-thin lumen walls.…”

Communal interaction of glycation and gut microbes in diabetes mellitus, Alzheimer's disease, and Parkinson's disease pathogenesis

“…As an epigenetic concern, Nativio et al 47 highlight potential epigenetic strategies for early‐stage AD treatment and provide alternative avenues for possible intervention. Recently, Chen et al 388 proposed a novel platform technology solution for treating AD. The researcher evidenced that the clearance of the plan may help relieve the cognitive impairment related to AD based on microtube array membrane encapsulated cell therapy.…”