Abstract

Alzheimer’s disease (AD) remains a major neurodegenerative disorder with limited disease-modifying options. Current FDA-approved drugs, including anti-amyloid monoclonal antibodies, offer only modest benefits and can induce amyloid-related imaging abnormalities. To address this, we developed a Microtube Array Membrane-Encapsulated Cell Therapy (MTAM-ECT) system that encapsulates human umbilical cord mesenchymal stem cells (hUC-MSCs) within biodegradable PLA-PLGA microtubes for subcutaneous implantation.

The ultra-thin, porous MTAM structure maintains long-term hUC-MSC viability and enables continuous release of therapeutic exosomes capable of crossing the blood–brain barrier. In vitro, encapsulated hUC-MSCs retained ~75% viability over 42 days and significantly reduced phosphorylated Tau (pTau) in SH-SY5Y AD models. In vivo, APP/PS1 transgenic mice implanted with MTAM-ECT showed improved cognition in the Novel Object Recognition test, reduced cortical pTau deposition, and increased NeuN/PSD95 expression compared with untreated or intravenously injected groups.

Subcutaneous implantation was well tolerated without inflammation or systemic toxicity, as verified by GLP-certified USP 88 tests. This minimally invasive and long-acting MTAM-ECT platform provides sustained neurorestorative effects and may overcome key limitations of conventional stem-cell therapy. Ongoing translational studies aim to advance this approach to first-in-human clinical evaluation in Taiwan.