New device improves stem cell generation for Alzheimer's therapy

Researchers in Sweden say they have perfected a technique for converting normal skin cells into neural stem cells, which they believe is moving closer to affordable personalized cell therapies to treat Alzheimer's disease and Parkinson.

Using a custom-designed microfluidic device, the research team has developed an unprecedented and accelerated approach to reprogram human skin cells into induced pluripotent stem cells (iPSCs) and then develop them into neural stem cells.

The study's first author, Saumey Jain, says the platform could improve and reduce the cost of cell therapy by making the cells more easily compatible and accepted by the patient's body. The study was published in Advanced Science by scientists from the Royal Institute of Technology KTH.

Anna Herland, senior author of the study, said the study demonstrated the first use of microfluidics to guide iPSCs to become neural stem cells.

Neural stem cells differentiated using a microfluidic platform. Photo: KTH Royal Institute of Technology

The transformation of ordinary cells into neural stem cells is actually a two-step process. Cells are first exposed to biochemical signals that induce them into pluripotent stem cells (iPSCs), which can generate various cell types.

They are then transferred to a culture that mimics the signals and developmental processes involved in the formation of the nervous system. This stage, called neural differentiation, redirects cells towards the neural stem cell pathway.

Over the past ten years, laboratory environments for such work have gradually shifted from traditional plates to microfluidic devices. Herland says the new platform represents an improvement in microfluidics for both steps: iPSC generation and neural stem cell differentiation.

Using cells from human skin biopsies, the researchers found that the microfluidic platform enabled cells to commit to a neural fate at an earlier stage than those differentiated in conventional plates.

“We document that the confined environment of the microfluidic platform enhances the commitment to generate neural stem cells,” says Herland.

The closest view of a microfluidic chip used for stem cell induction. Photo: KTH Royal Institute of Technology

Jain says the microfluidic chip can be easily fabricated using polydimethylsiloxane (PDMS), and its microscopic size offers significant savings on reagents and cellular material.

The platform can be easily modified to adapt to differentiation into other cell types, he adds. It can be automated, providing a closed system that ensures consistency and reliability in the production of highly uniform populations of cells.

Overview of research including device fabrication, reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), and neural induction of iPSCs using the dual SMAD inhibition protocol to generate neural stem cells.
a) Fabrication process of a microfluidic device with 0.4 and 0.6 mm high channels for somatic cell reprogramming (R) and neural induction (N), respectively. Channel volumes and total volume are indicated in the table.
b) Overview of the process of reprogramming somatic cells into iPSCs on microfluidic devices and plates using mRNA transfection.
c) Overview of the process of neural induction of iPSCs into neural stem cells on microfluidic devices and plates using the SMAD dual inhibition protocol.
Source: Advanced Science (2024). DOI: 10.1002/advs.202401859

“This is a step towards making personalized cell therapies for Alzheimer's and Parkinson's diseases accessible,” adds Jain.

Scientists from the Karolinska Institutet and Lund University also took part in the study, collaborating in the IndiCell consortium.