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

Int J Mol Sci. 2022 Jun 20;23(12):6855. doi: 10.3390/ijms23126855.

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.

Keywords: Alzheimer’s disease (AD); encapsulated cell therapy; microtube array membrane (MTAMs); neurodegenerative disease; passive immunotherapy.

MeSH terms

  • Alzheimer Disease* / therapy
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cell- and Tissue-Based Therapy
  • Cognitive Dysfunction*
  • Immunization, Passive
  • Mice
  • Technology
  • tau Proteins / genetics
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • tau Proteins

Grants and funding

International Laboratory funding scheme (NeuroTMULille) is supported by the University of Lille and TMU. This research was funded by Programmes d’Investissements d’Avenir LabEx (excellence laboratory), DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to Alzheimer’s disease).