Recently, the media was flooded with news about the first person cured of diabetes, sparking great excitement and curiosity. These reports highlighted the groundbreaking work of Chinese scientists developing stem cell-based therapies. Until now, you may have heard this term mainly in connection with Vertex Pharmaceuticals, which achieved a historic milestone in 2021. For the first time, stem cells were used to treat type 1 diabetes in a human, successfully curing Brian Shelton of this disease.

One of the most common questions the public asks on this topic is whether one’s own umbilical cord blood is needed to create such stem cells. The answer is that it is not necessary, as scientists can reprogram cells into pluripotent (universal) cells from any type of cells, such as skin cells (more details below).

So, how are the Chinese scientists approaching this differently? The key difference lies in their method of reprogramming cells. While other teams, like Vertex, use genetic engineering to alter cells, the Chinese scientists use chemicals instead. It remains to be seen if this approach will offer a safer and more affordable option for treating diabetes and other diseases. INNODIA and its Managing Director, Manuela Battaglia, invited Professor Deng, a member of this Chinese research team, to help us better understand the actual progress in science, cutting through the media buzz.

I was honored to participate in ‘Tuesdays with INNODIA‘ and listen to the professor live. Among the more than 100 participants, there were several Slovak names, which genuinely pleased me and confirmed that the Slovak diabetes community is interested in being at the forefront when it comes to discussions on type 1 diabetes.

This summary of the presentation (plus a little extra) is intended mainly for those who couldn’t attend due to language barriers and who asked me to share the content with them.

Prof. Hongkui Deng: Visionary in Regenerative Medicine

Professor Deng’s career spans several prestigious institutions, including Wuhan University, Shanghai Medical College, UCLA, and NYU School of Medicine. He also served as a Research Director at ViaCell, a biotech company in Boston specializing in stem cell research.

In 2000, after receiving a prestigious award from the Chinese government, Deng returned to China. He’s leading a research team at Peking University. His initial work focused on diabetes and human embryonic stem cells. During the SARS epidemic, Deng also contributed to research on treatments and vaccines. In 2006, he received a grant from the Bill and Melinda Gates Foundation to work on vaccines for HIV and hepatitis C.

Advancements in Stem Cell Research and Historical Milestones

Professor Deng’s laboratory has been a pioneer in the development of chemically induced pluripotent stem cells (hCiPSCs), which show significant promise in treating Type 1 diabetes (T1D). This innovative technique opens new possibilities for creating insulin-producing cells. During the meeting, the professor shared his team’s advancements over the past two decades.

He began his presentation by emphasizing the crucial role pluripotent stem cells play in regenerative medicine, which has led to new possibilities for personalized treatment (tailored to individual patients).

Key milestones in cell reprogramming began with the work of Professor Sir John Gurdon (back in 1962), who focused on somatic cell nucleus transfer. This research was later expanded by Professor Shinya Yamanaka in 2007, who developed the technology for induced pluripotent stem cells (iPSCs). This technique enables scientists to create and genetically reprogram adult cells, such as skin cells, into any other type of cell, including insulin-producing cells. The significant contributions of Gurdon and Yamanaka earned them the Nobel Prize in 2012 and paved the way for further research in this field.

In 2013, researchers made a significant breakthrough by reprogramming mouse cells into pluripotent stem cells using chemical compounds, rather than genetic methods. This marked the beginning of a new era in non-genetic methods for creating versatile cells, ultimately leading to the development of human chemically induced pluripotent stem cells (hCiPSCs).

Recent studies and findings

In 2022, a study by Guan et al., published in Nature, focused on advancements in research involving human chemically induced pluripotent stem cells (hCiPSCs). The study demonstrated how the fate of these cells can be controlled through external stimulation (Guan et al., 2022). The potential applications of hCiPSCs are extensive; they can be used to treat immunological diseases, diabetes, liver failure, heart diseases, neurodegenerative disorders, kidney failure, and macular degeneration. Additionally, they can be utilized for disease modeling, drug testing, and cell therapy.

Clinical transplantation of pancreatic islets, recognized as a treatment for type 1 diabetes (T1D) based on a study published in 2000 in The New England Journal of Medicine, has had a significant impact on this area of research. The well-known Edmonton Protocol, established over 20 years ago, involves the removal of the pancreas, isolation of the islets, and their injection into the portal vein of the liver. This procedure highlighted the limitations of relying solely on islets from human donors and underscored the urgent need for alternative sources of insulin-producing cells, such as human pluripotent stem cells (Shapiro et al., 2000).

Deng also mentioned his PhD work at UCLA, documented in the journal J. Exp. Med. (1993, 178:1675-1680). He took us through 20 years of research experience from their laboratory on stem cell-derived islets. Here are some key milestones in their work:

• First stepwise protocol: The laboratory developed the protocol for generating insulin-producing cells from mouse and human embryonic stem cells (Y. Shi et al., Stem Cells, 2005; Jiang Wei et al., Cell Research, 2007).
• Creation of pancreatic beta cells: In 2009, they successfully created pancreatic beta cells from human induced pluripotent stem cells (iPSCs) (Zhang et al., Cell Research, 2009).
• Labeling key genes: The laboratory also focused on labeling key genes to track the development process of human pancreatic beta cells (Liu et al., Cell Research, 2014).
• Recent advancements: In 2022, they developed a robust and highly efficient protocol for generating functional islets derived from human chemically induced pluripotent stem cells (hCiPSCs) (Du et al., Nature Medicine, 2022). These hCiPSC-derived islets were transplanted into diabetic macaques through intraportal infusion, demonstrating their efficacy.

Historically first: Successful autologous transplantation of chemically treated stem cells in a person with type 1 diabetes

The final part of the presentation focused on what we were all waiting for: the transplantation of islets derived from chemically induced pluripotent stem cells into the abdominal area of the first human patient with type 1 diabetes (Cell, 2024). This was the first case where chemically treated stem cells were successfully used in a human, this time in a woman, marking a transition from previous studies in macaques to human applications. In addition to the method of creating the transplanted cells and the site of application, the uniqueness of the procedure lay in the fact that the so-called autologous, or the patient’s own cells, were used for reprogramming.

After the transplantation, there was complete independence from insulin, with fasting blood glucose (FBG) levels maintained below the diabetes threshold. There was also a significant improvement in time in range (TIR), exceeding 98%, and HbA1c levels below 5.7, which are considered normal values for a healthy individual, during annual follow-up.

The cells demonstrated strong function, with C-peptide levels increasing as early as the second week after transplantation. After 180 days, the patient showed further improvement in glucose tolerance (oral glucose tolerance test; OGTT). According to the results from monitoring the site of transplantation using magnetic resonance imaging (MRI), the grafts remained stable, and no signs of teratoma formation (a type of tumor) were observed during the annual follow-up.

In summary, this transplantation led to a rapid reversal of diabetes, with the patient being independent of exogenous insulin from the 75th-day post-transplant, and no abnormalities were observed throughout the entire follow-up period.

Limitations and Future Directions

Deng notes that despite the promising results, this study has several limitations:

1. Long-term safety and efficacy: The safety and efficacy of the transplantation beyond one year and in a broader patient population still need to be thoroughly evaluated. Further studies involving a larger patient group are necessary (similar procedures have been performed on a couple of other patients).
2. Use of immunosuppressants: The administration of immunosuppressants limited the assessment of the recipient’s immune response to the autologous transplant, particularly considering that type 1 diabetes (T1D) is an autoimmune disease. While these medications were necessary due to the patient’s previous liver transplant and did not pose an additional burden for her, they restricted the ability to gain insights into the related autoimmune response.

These findings highlight the need for further clinical studies in this area and represent a significant advancement in realizing the potential of personalized cell therapy.

The importance of collaboration

What excited me the most about Professor Deng’s presentation was not just the scientific discoveries, but also his emphasis on global collaboration. He continually highlighted the importance of international partnerships in advancing this research, and it is truly inspiring to see scientists from around the world coming together in the effort to improve treatments for type 1 diabetes (T1D).

This meeting provided a valuable opportunity to hear insights directly from the source, and the presence of experts like Skyler from the USA, Hussain from the UK, Bossi from Italy emphasized the need for deeper discussions on these critical topics. INNODIA plays an important role in this collaboration, creating an environment where people living with diabetes and their caregivers are at the center of attention alongside top experts from around the world.

Let’s change the future of diabetes with INNODIA.

I invite the community of people with diabetes, as well as institutions and organizations, to join INNODIA.

If you live with diabetes or care for someone who does, the INPACT community within INNODIA supports individuals and families affected by type 1 diabetes. This community ensures that their voices help shape patient-centered solutions. Become a INPACT Certified Associate and help shape the future of diabetes care.

What is INNODIA?
INNODIA is the largest European network focused on the prevention and cure of type 1 diabetes. It brings together experts from universities, research centers, hospitals, and non-profit organizations to collaborate on innovative projects and research.

Who is INNODIA for and how to join?
INNODIA is open to universities, research institutes, hospitals, and non-profit organizations that want to contribute to advancements in type 1 diabetes. Membership offers the opportunity to engage in innovative projects and share knowledge (and it is free).

We are looking for more certified centers in Eastern Europe, especially in Slovakia. If you belong to an organization that shares our vision, we encourage you to join INNODIA so that together we can bring new opportunities to the diabetes community.

For more information, visit INNODIA.org. I’m happy to answer any personal questions here.

Facts to Conclude

The uniqueness of the Chinese study lies in its reprogramming system, the use of the patient’s own cells, the establishment of criteria for release and safety, which serve as a benchmark for the future, the implantation site, and the possibility of freezing the cells.

Check out my related articles:

More about Vertex Pharmaceuticals and their approaches to treating type 1 diabetes

More about Brian, the first person cured of diabetes

VX-264 – The first study on the possibility of curing type 1 diabetes without immunosuppression

Why INNODIA

Milan Research Center for Diabetes Treatment: DRItti and voi – Directly to You 2024