The element destruction of liver cells brought on by excessive alcohol consumption and the resulting inflammation in severe Alcoholic Hepatitis are problems that continue to arise and affect everyone in almost all corners of the globe. Some of the patients that struggle with acute liver failure tend to deteriorate quickly. Because of the pattern of multiple organ systems failing to work, professionals are left in a very tough situation in search of a solution. Current pharmaceutical methods are inefficient for dealing with this issue and actively reversing this damage to the liver is a highly desirable remedy for many doctors. Fortunately, within the advancing field of Regenerative Medicine Thailand, UC-MSCs offer a much-needed and thoroughly desired option for the restoration of cell viability in a patient.
Pathological Alcoholic Hepatitis Mechanisms
To comprehend how liver cells respond to high volumes of alcohol consumption in Alcoholic Hepatitis, one must first understand how alcohol metabolism affects the body. The liver is where the metabolism of alcohol mainly occurs, producing highly reactive and toxic byproduct molecules of metabolism. These molecules damage DNA and overexert the oxidation and reduction control of the inner membranes and the organelles themselves. The damage caused by the hepatic system’s overdrive of control mechanisms leads to the release of damaged DNA to activated Kupffer cells. Exceedingly high amounts of Tumor Necrosis Factor, an inflammatory cytokine such as IL-6 and IL-13 and other injury-associated cytokines released in an unnecessary and rapid fashion lead to the death of liver cells. The microenvironment also leads to the injury and death of Stellate cells and to the formation of myofibroblasts, which leads to the deposition of a large amount of extracellular matrix. This results in the fibrosing and the rapid alteration of the architecture of the liver and the associated failure of the liver, creating a pathological cascade that researchers in Regenerative Medicine Thailand now target using cellular therapies like UC-MSCs. Alcoholic Hepatitis is characterized by the combination of continuous cell death and dynamic fibrosis, a destructive cycle that requires innovative therapeutic interventions like UC-MSCs within the landscape of Regenerative Medicine Thailand.
Figure 1: Pathological Alcoholic Hepatitis Mechanisms
Traditional Alcoholic Hepatitis Therapies
Typical treatments involve the use of corticosteroids, which are prescribed to suppress inflammation and control the immune response during acute episodes of Alcoholic Hepatitis. Corticosteroids decrease early mortality, but these agents are poorly tolerated by most patients and become associated with various morbidities, including increased risk of opportunistic and life-threatening infections. In the absence of corticosteroids, some clinicians use pentoxifylline, but the ability of pentoxifylline to improve long-term survival in these patients is limited. Liver transplantation is currently the only effective treatment. Despite the authoritative nature of liver transplantation in the treatment of end-stage liver disease, there are many barriers to the widespread implementation of this treatment. Liver transplant waiting lists are notably restrictive. Patients with Alcoholic Hepatitis who have not abstained will not be considered for transplantation, in addition to the waitlist restrictions. Due to these barriers, there is an important need for the development of new treatments within Regenerative Medicine Thailand, specifically exploring the therapeutic potential of UC-MSCs.
Why use UC-MSC?
The ability of UC-MSCs to alter the existing steatohepatitis provides a unique opportunity to use this cell type as an alternative to transplantation for severe cases of Alcoholic Hepatitis. The effectiveness of UC-MSCs is determined by their ability to provide effective paracrine signals. This ability to create a microenvironment of immunomodulation is accomplished through their secretomes. When UC-MSCs reach the liver, their stored secretomes concentrate in the liver, enabling the UC-MSCs to create an immunomodulatory microenvironment. UC-MSCs primarily release these secretomes to alter the immunological landscape by providing prostaglandin E2 and indoleamine 2,3-dioxygenase to suppress T cell activity, and by regulating inflammatory macrophages to provide more constructive and less inflammatory activity. The secretomes also provide hepatocyte growth factor, which is essential for liver regeneration, and vascular endothelial growth factor, highlighting why this approach is becoming a cornerstone of Regenerative Medicine Thailand.
These proteins secreted by UC-MSCs may aid the body’s natural ability to regenerate cells within the liver while also aiding the regeneration of blood vessels and the healthy architecture of tissue damaged by Alcoholic Hepatitis. Additionally, these cells may block the activation of hepatic stellate cells, conditioning the stellate cells to stop the build-up of the extracellular matrix. This cell-based technique, championed within Regenerative Medicine Thailand, is quite useful as it stops the chronic inflammation process at the same time as it is successfully restoring the functional repair process.
Figure 2: Comparative approaches to Alcoholic Hepatitis therapies
Future Directions
The advancement of biotechnology is required when developing cellular therapy. The treatment of certain diseases like Alcoholic Hepatitis by way of the use of UC-MSCs in Southeast Asia is developing quickly. Extending the reach of these therapies fits the concept of Regenerative Medicine Thailand’s vision which strives to position Thailand as Southeast Asia’s leading medical center. There are several high-tech research and development facilities in Thailand which optimize protocol investments on the cultivation of mesenchymal stem cells. The emphasis in research and development is on the development of standard operating procedure manufacturing in order to streamline therapeutic interventions. Thailand is the only country in Southeast Asia that has the capacity to link biotechnology research, clinical practice, and laboratory medicine. The emphasis on the treatment of severe liver disease is to target the biotechnological advanced interventions to shift the burden of disease in the Southeast Asia’s region.