Cell Therapies and iPSC Disease Modeling for Type 1 Diabetes
Author: Weiwei Liang
Highlights:
Lantidra, the first and recently FDA-approved (approved in June 2023) cell therapy to treat type 1 diabetes works by infusing allogeneic islet beta cells into the patient's body, enabling the secretion of natural insulin.
Advancements have been made in the field of induced pluripotent stem cells (iPSCs), cells induced in a petri dish, often from the patient's skin to be grown/cultured using specific growth factors to derive target cells.
A research team at Harvard University is transplanting three human cell types generated from iPSCs that are the key components of type 1 diabetes into mice to understand their mechanisms, with the goal of curating a cell therapy for patients.
Introduction
As mentioned in the previous two parts of the Global Diabetes Landscape Series, there are over 8.75 million people in the world who are diagnosed with type 1 diabetes. Currently, the most common treatments for patients with type 1 diabetes are exogenous insulin injections. However, the accessibility of continuous insulin injections often poses a challenge to populations in low to medium-income countries, which could lead to a lack of timely treatment thereby causing serious consequences such as infections and deaths. With the rise of cell therapies, there may be ways that financial assistance programs could be implemented for individuals who desperately need them but are unable to afford the treatment themselves.
In the last few years, cell therapy such as infusions and stem cell therapy has been on the rise for many diseases such as Diabetes, cancers, Alzheimer’s Disease, and more, and has been a popular area of research that many scientists have been studying. This article will focus on the current cell therapies for diabetic patients, specifically type 1 diabetic patients, and the ongoing research using induced pluripotent stem cells modeling type 1 diabetes.
The first FDA-approved cell therapy for type 1 diabetes - Lantidra
Cell therapy includes stem cell and non–stem cell-based forms of disease treatment using unicellular or multicellular therapies (El-Kadiry et. al). Specifically, a stem cell therapy is a method to transfer the patient’s own cellular material from their body, programmed into something with a treatment purpose back into a patient’s body to treat a medical illness. This is an innovative yet complex strategy to treat a disease, but found to be quite effective if successfully implemented. Lantidra, the first and recently FDA-approved (approved in June 2023) cell therapy to treat type 1 diabetes works by enabling the secretion of insulin by the infused allogeneic islet beta cells. Lantidra is administered as a single infusion into the hepatic (liver) portal vein. In some type 1 diabetes patients, the externally infused cells can produce enough insulin, so the patient no longer needs to take insulin, either by injections or pump, to control their blood glucose/sugar levels. An additional infusion of Lantidra may be injected depending on the patient’s individual response to the initial dose (FDA). This is a powerful method to treat type 1 diabetes, however, there are side effects that come with the treatment. These mainly include mouth sores and nausea depending on each patient, but overall there has not been any significant backlash on this therapy.
What are stem cells and iPSCs?
Stem cells are unique cells that stem from early stages of development, and have two distinctive properties: self-renewal and differentiation. These cells are found in nearly all of the tissues of the body, and they are vital for survival (Mayo Clinic). There are a few ways the body makes stem cells, including from the embryo (embryonic stem cells), from adult tissues such as bone marrow or fat, and from amniotic fluid as well as umbilical cord blood. These stem cells can transform into specialized cells that become our skin cells, eye cells, hair cells, and various types of cells that make humans human.
In the last decade since 2006, many advancements have been made in the field of induced pluripotent stem cells, also known as iPSCs. They are cells induced in a petri dish, often from the patient's skin to be grown/cultured using specific growth factors to derive target cells. These target cells can be the disease-causing cells, or cells that would cure the disease.
The idea of forming insulin-producing Beta cells using iPSCs
Induced pluripotent stem cells (iPSCs) are first derived from patient tissue biopsies, then reprogrammed to transform into stem cell-derived islet cells (SC-islets) that contain β (SC-β) cells (Cell Reports Medicine). The β-cells then start to produce insulin, therefore allowing the patient to self-generate insulin forever and replace the external injections of insulin treatment. The idea is that this therapy will work as a one-time treatment, and the patient never has to worry about remembering or obtaining expensive insulin injections again.
Diabetes disease modeling using iPSCs
Cell lines used to study type 1 diabetes are often created by using tools such as gene editing technologies like CRISPR to insert/omit and express foreign DNA into the cells. Creating various cell lines could be useful to study diseases known to deal with genetic mutations or variances, and to generate treatments specifically targeted to them. Many researchers including a research team at Harvard have dedicated their research to transplanting the three human cell types generated from iPSCs that are the key components of type 1 diabetes into mice in order to understand their mechanisms and purpose better. The three cell types are: beta cells, the immune cells that attack and destroy beta cells, and thymus cells. The team will produce each of these cell types from patient-derived iPSCs, and after injecting them into genetically engineered mice that lack immune systems, allowing them to accept transplants of human cells. The researchers will transplant each of the three cell types into the mice, creating a new research model in which patient-derived cells can interact to generate the disease state (Harvard Stem Cell Institute). Furthermore, using patient-derived iPSCs to develop these disease models will retain the mutations that the patients have, thereby replicating cells from a human with type 1 diabetes maximumly.
Overall, cell therapies such as Lantidra and IPSC disease modeling projects have been a major breakthrough in treating type 1 diabetes. Research work targeting type 2 diabetes has been in development as well, using tools such as CRISPR/Cas9 in human iPSCs. A great amount of high-impact research work has been dedicated to finding solutions for type 1 and type 2 diabetes, and the hope is that one day, diabetes will not be a global epidemic anymore.
References
Commissioner, Office of the. “FDA Approves First Cellular Therapy to Treat Patients with Type 1 Diabetes.” U.S. Food and Drug Administration, FDA, www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-type-1-diabetes. Accessed 5 May 2024.
“Diabetes.” Harvard Stem Cell Institute, Harvard University, hsci.harvard.edu/diabetes-0.
El-Kadiry, A. E., Rafei, M., & Shammaa, R. (2021). Cell Therapy: Types, Regulation, and Clinical Benefits. Frontiers in medicine, 8, 756029. https://doi.org/10.3389/fmed.2021.756029
Kristina G. Maxwell, Jeffrey R. Millman, Applications of iPSC-derived beta cells from patients with diabetes, Cell Reports Medicine, Volume 2, Issue 4, 2021, 100238, ISSN 2666-3791, https://doi.org/10.1016/j.xcrm.2021.100238.
“Stem cells: What they are and what they do.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 23 Mar. 2024, www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117#:~:text=Yes.,diseases%20such%20as%20heart%20.
