MSC-CM and its potential in diabetes treatment

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.

What is Diabetes Mellitus?

Diabetes mellitus, also known as diabetes, is a chronic metabolic disorder characterized by elevated blood sugar levels [1, 2]. The number of patients with type 2 diabetes continues to rise globally. According to the World Health Organization, this condition currently affects over 463 million people worldwide and accounts for 10% of healthcare costs [1]. Type 2 diabetes is a multifactorial disease caused by beta-cell dysfunction and insulin resistance in peripheral tissues, mainly due to complications in large blood vessels (related to coronary artery disease, peripheral artery disease, and stroke), as well as complications in small blood vessels (diabetic retinopathy) linked to the eyes, nerves, and kidneys. Typically, healthcare providers do not adequately treat these vascular complications, which carry a high risk of mortality.

Traditional Diabetes Treatment Methods

Traditional therapies for diabetes include insulin injections and complete pancreas cell replacement via transplantation. However, insulin injections are not a method of long-term treatment because they are unable to completely control and prevent complications [3]. Some type 2 diabetes patients may be insulin-resistant or experience sudden blood sugar drops after insulin injections, posing life-threatening risks. Additionally, healthcare providers can manage diabetes by implementing exercise and a proper diet along with certain medications (such as Metformin, Meglitinides, SGLT2 inhibitors, etc.). Alternatively, pancreatic transplantation or islet cell transplantation can yield some effectiveness in treating diabetes; however, they face certain obstacles, including immune rejection, limitations in donor sources, and the need for lifelong immune-suppressing medications [4]. Mesenchymal stem cell (MSC)-based therapies have emerged as an alternative treatment method because of their immune-modulatory capacity, anti-inflammatory properties, and prevention of pancreatic destruction [5].

Diabetes Treatment Using MSC-CM

Mesenchymal stem cells regulate innate and adaptive immune responses through cell-to-cell interactions and the secretion of soluble factors and cytokines [6]. Recent studies have shown that the beneficial effects of mesenchymal stem cells largely depend on their secretory activities. Therefore, instead of using cells directly, therapies utilizing conditioned media from culturing mesenchymal stem cells become safer and more promising[7]. Hence, conditioned media (CM) from MSC cultures, known as MSC-CM, containing bioactive factors and cytokines, is seen as a promising therapy for treating diabetes [8].

MSC-CM can inhibit the movement of immune cells into damaged tissues, induce M2 polarization of macrophages, increase the release of anti-inflammatory cytokines, and decrease the secretion of pro-inflammatory cytokines [9]. Activation factors and cytokines found in MSC-CM, such as TIMP-2, SPARC, MCP-1, VEGF, GDF-15, and angiopoietin-1a, act as regulators inhibiting insulin resistance. Thus, they improve insulin resistance in type 2 diabetes patients (Figure 1)[8]. Additionally, MSC-CM restores insulin signaling pathways, enhances ATP synthesis, and significantly reduces various reactive oxygen species (ROS) reactions in pancreatic cells [10]. MSC-CM administration to diabetic mice has demonstrated the ability to lower blood sugar levels and restore and increase insulin production in pancreatic cells [8]. These results show that MSC-CM can improve both type 1 and type 2 diabetes through multiple mechanisms.

Figure 1: Conditioned media from umbilical cord mesenchymal stem cells (UC-MSC-CM) contains components that restore insulin signaling pathways, enhance pancreatic function, and reduce ROS, inhibiting insulin resistance in type 2 diabetes patients[8].

Using MSC-CM in clinical treatment offers many advantages, such as ease of production, transportation, and evasion of immune rejection. Although providing similar efficacy to MSCs, MSC-CM does not trigger strong immune responses or the risk of tumor formation, making it safer for patients. While there have been experiments using MSC-CM in treating type 2 diabetes in animals, clinical trials on humans are still lacking. Preliminary preclinical data show the potential of MSC-CM therapy in treating diabetes and require further research on mechanisms and implementing clinical studies. In the future, therapy using MSC-CM could potentially replace traditional treatments to improve significantly the condition of diabetes, specifically, and metabolic disorders in general.

References

1. Xiao, Y., et al., The effects of omega-3 fatty acids in type 2 diabetes: A systematic review and meta-analysis. Prostaglandins Leukot Essent Fatty Acids, 2022. 182: p. 102456.
2. Kharroubi, A.T. and H.M. Darwish, Diabetes mellitus: The epidemic of the century. World J Diabetes, 2015. 6(6): p. 850-67.
3. Shah, R.B., et al., Insulin delivery methods: Past, present and future. Int J Pharm Investig, 2016. 6(1): p. 1-9.
4. Liu, M. and Z.C. Han, Mesenchymal stem cells: biology and clinical potential in type 1 diabetes therapy. J Cell Mol Med, 2008. 12(4): p. 1155-68.
5. Jurewicz, M., et al., Congenic mesenchymal stem cell therapy reverses hyperglycemia in experimental type 1 diabetes. Diabetes, 2010. 59(12): p. 3139-47.
6. Madec, A.M., et al., Mesenchymal stem cells protect NOD mice from diabetes by inducing regulatory T cells. Diabetologia, 2009. 52(7): p. 1391-9.
7. Ranganath, S.H., et al., Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell, 2012. 10(3): p. 244-58.
8. Kim, K.S., et al., Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell. Diabetes Metab J, 2021. 45(2): p. 260-269.
9. Ionescu, L., et al., Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action. Am J Physiol Lung Cell Mol Physiol, 2012. 303(11): p. L967-77.
10. Fealy, C.E., et al., Mitochondrial dynamics in skeletal muscle insulin resistance and type 2 diabetes. Transl Res, 2018. 202: p. 69-82.