Evaluation of chip-reprogrammed iPSCs for cell replacement therapy for Parkinson’s disease
(2025) MOBN03 20242Degree Projects in Molecular Biology
- Abstract
- Parkinson’s disease (PD) is a progressive neurodegenerative disease, characterized by degeneration of dopaminergic neurons, leading to notable difficulties with one’s movement. Among different treatment options, stem cell replacement therapies have been recognized as an option to not only treat disease symptoms but to address its underlying cause- neuronal degeneration. This can be achieved through the implantation of neuronal progenitor cells derived from stem cells. Human induced pluripotent stem cells (iPSCs) offer a promising source for autologous cell therapies in neurodegenerative diseases such as PD, as they raise fewer ethical concerns and eliminate the need for a patient to be immunosuppressed compared to embryonic stem cells... (More)
- Parkinson’s disease (PD) is a progressive neurodegenerative disease, characterized by degeneration of dopaminergic neurons, leading to notable difficulties with one’s movement. Among different treatment options, stem cell replacement therapies have been recognized as an option to not only treat disease symptoms but to address its underlying cause- neuronal degeneration. This can be achieved through the implantation of neuronal progenitor cells derived from stem cells. Human induced pluripotent stem cells (iPSCs) offer a promising source for autologous cell therapies in neurodegenerative diseases such as PD, as they raise fewer ethical concerns and eliminate the need for a patient to be immunosuppressed compared to embryonic stem cells (ESCs). The workflow to reprogram somatic cells into iPSCs and subsequently iPSCs into ventral midbrain (VM) mesencephalic dopaminergic (mesDAergic) progenitor is labour-intensive, time-consuming and expensive; therefore, there is a critical need for improving the manufacturing process. Reprogramming with the use of a microfluidic device offers an automated and scalable alternative to manual iPSC generation. In this study, efficiency and consistency in generating ventral midbrain (VM) mesencephalic dopaminergic (mesDAergic) progenitor cells from chip-reprogrammed iPSCs were evaluated. Two donor-derived iPSC lines reprogrammed using either conventional or chip-based (microfluidic) methods served as a pluripotent starting point for differentiation into mesDAergic progenitor cells through controlled exposure to specific developmental cues. The goal was to assess if reprogramming method used compromises the quality of the differentiation protocol outcome. Additionally, we investigated the potential differences that might be related to donor sources. Two donor-derived lines were subjected to differentiation into VM mesDAergic progenitors. One of two tested lines demonstrated comparable differentiation potential across both reprogramming methods. Subsequently, conventionally and chip-reprogrammed cells of this cell line were successfully differentiated into mature neurons. Those results were analysed based on the detection of specific VM mesDAergic progenitor markers as well as mature neuronal markers. The other tested line failed to differentiate into VM mesDAergic progenitors, when reprogrammed conventionally but succeeded when reprogrammed using the chip platform. It may be an indication of donor-related variability or method-dependent reprogramming efficiency. However, it is not easy to understand the interaction between the reprogramming method, donor background and other sources of variability and to point out one specific reason for such an outcome. Achieving this could bring us closer to the widespread use of iPSCs, enabling personalized medicine to prevent or reverse conditions like Parkinson’s disease, diabetes, spinal cord injuries, and others. (Less)
- Popular Abstract
- The science of second chances
When organs fail, we usually step in trying to manage the damage. Drugs try to compensate for what the body can no longer do- regulating hormones, suppressing inflammation, or boosting missing chemicals; machines try to overtake lost function: dialysis for kidneys or pacemakers keeping damaged hearts beating. But what if we didn’t just help the failing organ? What if we could give it another chance by helping to restore what is missing or not working? Maybe we could start over?
Stem cells have a unique ability to become almost any type of cell: a neuron, a muscle cell or a liver cell. Tissue-specific stem cells are already present in our bodies, being responsible for repair and renewal processes- for... (More) - The science of second chances
When organs fail, we usually step in trying to manage the damage. Drugs try to compensate for what the body can no longer do- regulating hormones, suppressing inflammation, or boosting missing chemicals; machines try to overtake lost function: dialysis for kidneys or pacemakers keeping damaged hearts beating. But what if we didn’t just help the failing organ? What if we could give it another chance by helping to restore what is missing or not working? Maybe we could start over?
Stem cells have a unique ability to become almost any type of cell: a neuron, a muscle cell or a liver cell. Tissue-specific stem cells are already present in our bodies, being responsible for repair and renewal processes- for example, producing new skin or blood cells. However, neurons are not formed in the adult brain and for many years this potential has primarily been studied in the context of pluripotent stem cells derived from early, pre-implantation embryos- embryonic stem cells (ESCs). A breakthrough discovery by Yamanaka showed that we can create pluripotent stem cells by reprogramming mature cells back to a stem cell state. Those induced pluripotent stem cells (iPSCs) can be afterwards differentiated into another cell type. It builds the foundation of personalized therapies, as by using patients’ own cells, we could avoid the need for immunosuppression, which comes with serious risks and side effects.
One of the diseases that could be treated with stem cells is Parkinson’s disease, characterized by the loss of neurons that produce dopamine. Therefore, creating new early-stage neurons from stem cells and implanting them in the brain could restore lost functions- a concept already demonstrated using embryonic stem cells taken from early-stage, pre-implantation embryos. However, their use raises ethical concerns in some countries and requires immunosuppression to prevent rejection of the transplant.
The future is now
Many scientists are working towards translating iPSCs from the lab bench into clinical use. There are ongoing clinical trials aiming to test this approach’s effectiveness, safety and potential to use it in patients. We are entering a new era in medicine, where ‘rebuilding’ organs is no longer a science fiction concept.
Currently, ongoing efforts are focused on making these therapies more affordable, accessible, and safer for patients worldwide. Automating the cell manufacturing process, speeding it up, and making it more efficient are key goals of many research facilities. One of the approaches to make it happen is applying a faster, easier and cheaper reprogramming method, such as a microfluidic chip. In this study, we check if such a solution compromises cells’ ability to later differentiate into different cell types. Simultaneously, we explore the differences related to sources of the cells- different human donors.
If the field succeeds and brings iPSC therapies into everyday medical practice, the view on treating certain diseases will be completely transformed, offering patients a completely new quality of life. Because every organ, every body, deserves a second chance.
Master’s Degree Project in Molecular Biology; 60 credits 2025
Department of Biology, Lund University
Advisors: Malin Parmar, Jana Bonsberger
Unit/Department: Developmental and Regenerative Neurobiology, Faculty of Medicine, Lund University (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9214791
- author
- Staryk, Julia
- supervisor
-
- Malin Parmar LU
- Jana Bonsberger LU
- organization
- course
- MOBN03 20242
- year
- 2025
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9214791
- date added to LUP
- 2025-11-03 13:07:57
- date last changed
- 2025-11-03 13:07:57
@misc{9214791,
abstract = {{Parkinson’s disease (PD) is a progressive neurodegenerative disease, characterized by degeneration of dopaminergic neurons, leading to notable difficulties with one’s movement. Among different treatment options, stem cell replacement therapies have been recognized as an option to not only treat disease symptoms but to address its underlying cause- neuronal degeneration. This can be achieved through the implantation of neuronal progenitor cells derived from stem cells. Human induced pluripotent stem cells (iPSCs) offer a promising source for autologous cell therapies in neurodegenerative diseases such as PD, as they raise fewer ethical concerns and eliminate the need for a patient to be immunosuppressed compared to embryonic stem cells (ESCs). The workflow to reprogram somatic cells into iPSCs and subsequently iPSCs into ventral midbrain (VM) mesencephalic dopaminergic (mesDAergic) progenitor is labour-intensive, time-consuming and expensive; therefore, there is a critical need for improving the manufacturing process. Reprogramming with the use of a microfluidic device offers an automated and scalable alternative to manual iPSC generation. In this study, efficiency and consistency in generating ventral midbrain (VM) mesencephalic dopaminergic (mesDAergic) progenitor cells from chip-reprogrammed iPSCs were evaluated. Two donor-derived iPSC lines reprogrammed using either conventional or chip-based (microfluidic) methods served as a pluripotent starting point for differentiation into mesDAergic progenitor cells through controlled exposure to specific developmental cues. The goal was to assess if reprogramming method used compromises the quality of the differentiation protocol outcome. Additionally, we investigated the potential differences that might be related to donor sources. Two donor-derived lines were subjected to differentiation into VM mesDAergic progenitors. One of two tested lines demonstrated comparable differentiation potential across both reprogramming methods. Subsequently, conventionally and chip-reprogrammed cells of this cell line were successfully differentiated into mature neurons. Those results were analysed based on the detection of specific VM mesDAergic progenitor markers as well as mature neuronal markers. The other tested line failed to differentiate into VM mesDAergic progenitors, when reprogrammed conventionally but succeeded when reprogrammed using the chip platform. It may be an indication of donor-related variability or method-dependent reprogramming efficiency. However, it is not easy to understand the interaction between the reprogramming method, donor background and other sources of variability and to point out one specific reason for such an outcome. Achieving this could bring us closer to the widespread use of iPSCs, enabling personalized medicine to prevent or reverse conditions like Parkinson’s disease, diabetes, spinal cord injuries, and others.}},
author = {{Staryk, Julia}},
language = {{eng}},
note = {{Student Paper}},
title = {{Evaluation of chip-reprogrammed iPSCs for cell replacement therapy for Parkinson’s disease}},
year = {{2025}},
}