OH Baby! Type 1 Diabetes Treatments Stemming from Stem Cells
By: Alex Parrott and James LeFevre
Stem cells are an incredibly useful and versatile tool to treat a spectrum of diseases, and for type 1 diabetes (T1D), this is especially true. Shortages of pancreas donors, complications associated with transplantations and high costs have all driven the search for new methods of restoring insulin production in patients. But, successfully curing T1D is no small feat, so how do we develop safe and effective stem cell therapies for T1D? What can we learn from current stem cell therapies for T1D?
Promising stem cell therapies
One stem cell therapy for T1D called ProTrans is currently in clinical trials. Developed by NextCell Pharma, ProTrans is a cell suspension of Wharton’s jelly-derived mesenchymal stromal cells that have immunoprivileged and immunosuppressive effects, which may be useful in averting autoimmune attack. In this combined phase I and phase II study, phase I involves dose escalation while phase II involves randomization, double-blinding and placebo control. The goal of the study is to investigate the safety and tolerance of ProTrans when administered intravenously to type 1 diabetics.
Another application of stem cell therapy is treating retinal degenerative diseases. Currently being studied, human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cell transplants have proven effective in the treatment of macular degeneration in mice. These studies are very promising, but, as with most types of cell therapies today, how can efficiency be increased and common issues like immunogenicity be optimized? A study done by the Key Lab of Visual Damage and Regeneration & Restoration at the Southwest Hospital of Chongqing, China has a promising method of improving upon hESC-RPE cell therapy. Using layer by layer (LbL) assembly to embed the cells with polyelectrolytes gelatin and alginate, researchers were able to successfully reduce immunogenicity while increasing cell engraftment and visual function. How can positive results like this be applied to T1D research?
Improving stem cell therapies
Although promising stem cell therapies are available, improving them is imperative. Advancements in regenerative medicine can make the difference between treating T1D and curing it.
A review article, by Zonderland and Moroni, describes in-detail the significant role of mechanobiology in regenerative medicine and how it may improve stem cell therapies. The review focuses on mesenchymal stromal cells due to their wide use in regenerative medicine and highly mechanotransduction dependent differentiation. The authors note that 3D culture is needed to better understand mechanotransduction pathways. More research on mesenchymal stromal cells and other stem cells in 3D can enhance tissue engineering scaffold designs for stem cells and contribute to the advancement of regenerative medicine.
Luckily, 3D studies have been done and have provided promising results, thus further supporting their necessity. Robins, Morgan, Krueger, and Carson, bioengineered a 3D culture of Trophoblast cells to see if they could develop vesicles in a substrate free environment. Trophoblast naturally forms 3D structures that allow for cell to cell interactions, something that typical 2D methods cannot do, therefore limiting their observation of what is going on. They used a nonadhesive agarose hydrogel to form molds as a median into which the cells were seeded. Once the study was completed, the results showed that the trophoblast cells were able to form vacuoles over time, thus opening up many different areas for study involving microtissue formation and placental cell interactions.
Apart from mechanobiology and 3D cell culture, studying oxygen supply and its relationship to cell development might also prove beneficial. In a review article by Soares and colleagues, the researchers state that oxygen supply is crucial for placental development. Manipulating oxygen supply, specifically hypoxia, can be used as a tool to better understand placentation. Perhaps, hypoxia may also be useful in investigating developmental events in trophoblast and mesenchymal cells.
Where does this lead us?
By further studying placental cell interactions in 3D and improving vascularization and oxygenation, far more effective stem cell therapies for diabetes will be in reach. Successfully optimizing these processes will allow for better cell engraftment, which in turn will promote positive results and acceptance of the islet transplant.