Stem Cells and the Search For a Type 1 Diabetes Cure

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New stem cell-based therapies have emerged as a promising option for treating diabetes. The use of stem cells derived from umbilical cord tissue offers a potential solution to the problem of insulin deficiency, which is the hallmark of diabetes.

These stem cells can generate islet cells that can produce and secrete insulin, reducing or eliminating the need for exogenous insulin. This novel approach effectively lowers glucose levels and insulin requirements in first and most patients. One of the advantages of these stem cell-based therapies is that a single infusion of the cells can provide long-term benefits, potentially reducing the need for multiple treatments and lifelong insulin therapy.

This is a revolutionary approach to treating diabetes and can potentially improve the quality of life of individuals living with the disease by creating new insulin-making cells derived from stem cells

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Stem cells for Type 1 Diabetes

Stem cells for Type 1 diabetes is an exciting new treatment option that has been extensively studied recently. Type 1 diabetes, or juvenile diabetes, is an autoimmune disease that influences immune cells to destroy the insulin-producing beta cells in the pancreas. This leads to a lack of insulin, a hormone that regulates blood sugar levels, and requires patients to monitor their blood sugar and administer insulin injections constantly.

Mesenchymal stem cells (MSCs) have shown great promise as a potential treatment for Type 1 diabetes. MSCs are adult stem cells in various tissues, such as umbilical cord tissue, bone marrow, and fat.  Stem cells can reduce inflammation, modulate the immune system and differentiate into different cell types.

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"The International Diabetes Federation predicts that by 2045, nearly 700 million adults will have diabetes. The cause of diabetes, specifically Type 1 diabetes (T1D), is not fully understood, but research suggests a combination of genetic, environmental, and viral factors may contribute to its development. Currently, the most widely used treatment for T1D is administering insulin externally, but it does not provide a cure for the disease." (1)

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Stem cell Type 1 Diabetes cure

It is currently unknown if stem cell therapy is a definitive cure for Type 1 diabetes. While studies have shown promising results with the use of mesenchymal stem cell derived from various sources as a treatment for Type 1 Diabetes, with some studies reporting that the transplanted MSCs were able to differentiate into insulin-producing cells and improve blood sugar control, more research is needed before stem cell therapy can be considered as a cure for human patients.

Stem cells for Type 1 diabetes are an exciting new treatment option because it has more potential to provide a functional cure than traditional treatment methods.  By transplanting MSCs into patients with Type 1 diabetes, researchers hope to replace the destroyed beta cells, allowing the patient's body to produce insulin again.

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What is Type 1 Diabetes?

Type 1 diabetes (T1D) is a diverse disorder that destroys pancreatic beta cells, leading to a complete lack of insulin. Most cases are caused by an autoimmune attack on the beta cells (type 1a), while a small number of cases are caused by unknown or idiopathic destruction of the beta cells (type 1b).

T1D is responsible for 5-10% of all diabetes cases worldwide. The more common form of diabetes, type 2 diabetes (T2D), is characterized by resistance to insulin and a lack of sufficient insulin production. (2)

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Stem cell biology suggests promise as a way to treat diabetes

Stem cells are considered an up-and-coming new treatment option for Type 1 diabetes due to their ability to differentiate into multiple cell types and regenerative capabilities. Their versatile differentiation potential makes stem cells a promising treatment option for repopulating damaged tissues. Mesenchymal stem cells (MSCs), in particular, have gained significant attention in treating Type 1 diabetes due to their ability to regulate fibrosis and tissue regeneration, modulate the immune system, and produce various molecules that aid in treating type 1 diabetes, such as cytokines and exosomes.

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Immune system modulation plays a vital role

Also, MSCs have been shown to have immunomodulatory properties, which means that they can help suppress the immune response responsible for destroying the beta cells in the first place. This means that stem cell treatment may replace the lost beta cells and prevent further destruction of these cells.

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"Stem cells can promote the formation of new blood vessels by releasing specific proteins like the essential fibroblast growth factor and VEGF. They also play a vital role in regulating the immune system by moving to areas of inflammation and changing the characteristics of cells like dendritic cells, T cells, B cells, and natural killer cells. MSCs can decrease the production of pro-inflammatory proteins and avoid being killed by T cells, inhibit the maturation of dendritic cells, and reduce the growth of T lymphocytes by promoting the production of regulatory T cells through TGF-beta1, HGF, and nitric oxide. "

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Clinical trial results for Type 1 diabetes (T1D)

Several studies on animal models of Type 1 diabetes have shown promising results using MSCs as a treatment. Some studies report that the transplanted MSCs could differentiate into insulin-producing cells and improve blood sugar control. However, more research is needed before stem cells for Type 1 diabetes can be translated into a treatment for human patients.

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Mesenchymal stem cells (MSCs) have been proposed to have a role in Diabetes and other conditions through various mechanisms. These include homing to the site of injury and regulating the immune system. One review found that MSCs can effectively lower fasting blood sugar, C-peptide, and hemoglobin A1c levels and treat microvascular complications associated with T1D. (1) However, the exact cause of T1D is poorly understood, making it challenging to develop new treatments.

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Stem cell clinical trials for Type 1 diabetes

Research using stem cells for diabetes has been overwhelmingly positive, showing promising results for treating type 1 and 2 diabetes. The use of stem cells in treating diabetes has been shown to improve blood sugar control and potentially restore the function of insulin-producing beta cells in the pancreas. This is particularly important for patients with type 1 diabetes who depend on insulin injections for their entire lives.

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"According to a phase I/II randomized placebo-controlled clinical trial study conducted in June 2022, The use of MSCs in transplantation has been found to lead to improvements in HbA1c levels, a shift in the balance of cytokines in the blood from pro-inflammatory to anti-inflammatory, an increase in the number of regulatory T-cells in the peripheral blood, and an improvement in overall quality of life.  Patients experienced rapid and robust improvements after stem cell infusion." (3)

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Early transplantation of MSCs, in particular, was shown to significantly impact HbA1c and C-peptide levels, as well as a shift in pro-inflammatory cytokines to anti-inflammatory cytokines. Additionally, combining exercise with MSCs transplantation enhanced the benefits, improving glycemic and immunologic indices. (3)

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Why use mesenchymal stem cells?

Mesenchymal stem cells (MSCs) have a superior biosafety profile in the human body and negligible risk of tumorigenicity compared with induced pluripotent, hematopoietic stem cells or embryonic stem cells.  This makes them an attractive option for treating or reversing diabetes due to their ability to modulate the immune system and promote regeneration, lack of immune response due to the absence of major histocompatibility complex (MHC) class II, and their ability to target damaged pancreatic islets and nearby lymph nodes.

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Current stem cell research for Diabetes limitations

There are several limitations in the current stem cell research. One limitation is the need for larger sample sizes to provide more robust and definitive results. Because stem cell therapies are still relatively new and experimental, the sample sizes of many clinical trials to date have been small, making it difficult to draw definitive conclusions about the long-term efficacy of these therapies. Phase III studies with more patients who receive multiple doses of MSC injections and longer follow-ups are needed to elucidate the therapeutic effects of MSCs in T1D and shed light on the molecular mechanisms and pathways behind this process.

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What is Type 2 Diabetes?

Type 2 diabetes (T2D) is a chronic condition characterized by high blood sugar levels due to the body's inability to use insulin properly. Insulin is a hormone that regulates the absorption of sugar from the bloodstream into the body's cells for energy.

In type 2 diabetes, either the body does not produce enough insulin, or the cells do not respond appropriately to insulin, leading to a buildup of sugar in the blood. This can lead to various health complications over time if left untreated.

Type 2 diabetes is the most common form of diabetes, usually appearing in adulthood, and is closely associated with obesity and lifestyle factors such as poor diet and lack of physical activity.

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Is there a cure for Diabetes?

There is currently no cure for Diabetes.  Challenges to finding a cure for diabetes have primarily revolved around finding a method to replace or replenish b-cells.  In the past, the most effective treatment was a b-cell transplant to increase the number of healthy b-cells in a patient.

However, this procedure was undesirable for a multitude of reasons. The minimal number of b-cells required for a single transplant required 2-3 healthy donors. Additionally, the regimen of immunosuppressive drugs needed to prevent the body from rejecting the donor cells was strenuous for the recipient.

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Can stem cells treat Diabetes?

Researchers are now turning to stem cells to achieve a high number of new b-cells without the adverse effects of a transplant. After being introduced into a patient, the stem cells migrate to the damaged tissue, differentiate into new b-cells, and maintain a healthy level of b-cells in the body.

Alternatively, stem cells can be lab-grown and induced into becoming insulin-producing cells. These cells could then directly replenish depleted cells in a patient's body. With these methods, Type 1 diabetes could be successfully managed without the limited supply of donor cells.

Stem cells can be used similarly to treat Type 2 Diabetes. Although b-cells are still present in Type 2 patients, additional b-cells could supplement the body's supply to overcome the insulin resistance present in a patient. Treatment could aim to continuously maintain B-cell levels above the required amount to combat a patient's insulin resistance.

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Conclusion

Overall, research in the field of stem cells for diabetes has shown promising results in terms of improving glucose control and reducing the need for insulin replacement. A critical factor in the success of new stem cells is the target dose and the timing of when the treatment is administered. Studies have shown that early intervention with more stem cells may improve outcomes than lower doses or delayed treatment.

While pluripotent stem cells have received much attention in recent years, mesenchymal stem cells (MSCs) have emerged as a safer and more practical option for diabetes therapy due to their immunomodulatory and regenerative properties and negligible risk of tumorigenicity.

As regenerative medicine continues to advance, researchers and the chief medical officer need to continue investigating the optimal dosing and timing of stem cells and exploring new types of replacement cells, such as MSCs, to improve the management and treatment of diabetes.

Stem cells can potentially change how diabetes is treated, providing an innovative and practical approach to managing this chronic disease by managing glucose levels through glycemic control. With further research and development, we may be able to deliver therapies that can effectively replace lost insulin-producing cells and improve the quality of life of people living with diabetes.

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References

(1) Jayasinghe M, Prathiraja O, Perera PB, Jena R, Silva MS, Weerawarna PSH, Singhal M, Kayani AMA, Karnakoti S, Jain S. The Role of Mesenchymal Stem Cells in the Treatment of Type 1 Diabetes. Cureus. 2022 Jul 27;14(7):e27337. doi: 10.7759/cureus.27337. PMID: 36042996; PMCID: PMC9414788.

(2) Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ. Epidemiology of type 1 diabetes. Endocrinol Metab Clin North Am. 2010 Sep;39(3):481-97. doi: 10.1016/j.ecl.2010.05.011. PMID: 20723815; PMCID: PMC2925303.

(3) Izadi, M., Sadr Hashemi Nejad, A., Moazenchi, M. et al. Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial. Stem Cell Res Ther 13, 264 (2022). https://doi.org/10.1186/s13287-022-02941-w