Zewail City scientist Sameh Ali has joined a league of Egyptian researchers engaged in pre-clinical trials that use stem cells to explore a viable type 2 diabetes treatment by transforming mesenchymal stem cells (MS cells) – adult bone marrow stem cells – into insulin-producing cells (IPCs).
Mesenchymal stem cells are multipotentent, a feature that enables them to differentiate into different cell types including IPCs. MS cells are also a rich source of autologous stem cells that are derived from a patient’s own body, eliminating the risk of rejection.
In his latest, soon to be published, study, Ali is focusing on the aftermath of deriving IPCs from MS cells originating from diabetic patients; how the ‘modified’ cells (referred to in the study as ‘diabetic IPCs’) respond to increasing glucose stimulation compared to cells from healthy individuals.
Ali is collaborating with a team from the Urology and Nephrology Center (UNC) in Mansoura, led by urologist Mohamed Ghoneim who has previously used stem cell technology to cure a diabetic rodent; the scientists presented their promising results two years earlier and are still hoping they can replicate said results for humans.
“The new study is hoping to expand the potential of the clinical applicability of this research for humans,” Ali comments.
Ali’s study highlights the effect of type 2 diabetes on insulin secretion, mitochondrial function in addition to metabolic changes in MS cells before and after they differentiate into IPCs.
Ali explained in a Library of Alexandria lecture, partly sponsored by Nature Middle East and Nature Arabic Edition, that the main goal of the collaboration was to understand how can scientists control metabolism to control how MS cells differentiate into IPCs.
In their research, the scientists also observe the impact of the transplanted IPC clusters used to treat diabetes on mitochondria, which, in addition to being a powerhouse of the cell, play a crucial part in coordinating cellular signaling pathways implicated in insulin synthesis and secretion.
So far, the scientists found that, unlike in healthy subjects, IPCs derived from diabetic donors produce significantly higher levels of insulin in response to glucose stimulation, exhausting their metabolic machinery and essentially self-destructing on the long run. “During differentiation, cells start to rely more on mitochondria for fulfilling their bio-energetic demands. It appears that in stem cells derived from diabetic patients, this metabolic switch is somewhat defective,” explains Ali.
The study draws several conclusions about IPCs derived from previously defective MS cells, including highlighting a few adaptations in response to impaired glucose metabolism. Among these adaptations, for instance, are: ‘overcompensation’ in levels in molecules critical to insulin secretory function and an over-expression of genes related to insulin secretion augmentation.
These adaptations produce, among other symptoms, dysfunctional mitochondria and metabolically stressed differentiated cells.
Ali says that enhancing the process of differentiation is key to understanding how metabolism works; utilizing this understanding will enable them to expand the research to humans.