Background on Hepatic Emergencies
Acute Liver Failure is an irreversible emergency condition that rapidly compromises liver function. This rapid decline creates multi-system organ failure due to the synthetic and detoxification functions of the liver. The impact on patient mortality is significant and disruptions to normal life can occur in a matter of days. Patients in this condition have a great deal of physical pain and psychological pressure and there has historically been no solution to this condition. Medical professionals can only attempt to mitigate the rapid decline to more stable, chronic conditions. The main obstacle hepatocytes face in this condition is their inability to regenerate under extreme levels of acute inflammation. This condition represents an immense gap in the current medical landscape that necessitates novel therapeutics. A Stem Cell approach offers an intriguing potential solution. In this therapeutic model, the impact of UC-MSCs on the cellular level represents an extraordinary potential tool. Targeting the inflammatory drivers of hepatic necrosis using this Stem Cell model is a likely opportunity to positively impact the course of Acute Liver Failure.
Mechanisms of Cellular Restoration
To understand the therapeutic value of UC-MSCs, we must assess their ability to integrate within the hepatic microenvironment. Following systemic injection, these Stem Cell populations have a unique ability to navigate to areas of significant tissue injury and use paracrine signaling. Once they reach the site, they have intense, complex, and direct mechanisms of action, and they possess a secretome that includes hepatocyte growth factors and immunomodulatory cytokines. The secretome blocks the inflammatory cascade that typifies Acute Liver Failure. Furthermore, these Stem Cell agents directly transfer healthy mitochondria to distressed hepatocytes.
Tissue Engineering and Cell-Based Therapies
The remarkable effects of this bioenergetic Stem Cell therapy using UC-MSCs include the prevention of cellular apoptosis and the restoration of metabolic state. They also initiate a vital change in the polarization of macrophages. By switching nearby macrophages to an anti-inflammatory restorative phenotype, as opposed to a destructive pro-inflammatory phenotype, a favorable microenvironment for tissue healing is created. This UC-MSCs intervention stops the advancement of Acute Liver Failure and carries the potential for healing.
Limitations of Current Conventional Treatments
For those in the advanced stages of Acute Liver Failure, the now accepted standard of clinical care has largely revolved around supportive measures provided in the intensive care unit. The primary focus of these measures is the reduction of the most severe of the hepatic complications, such as brain edema, as well as the management of life-threatening overwhelming sepsis. Several systems of extracorporeal support may be used for the temporary blood depuration. However, all prevailing medical interventions function only as temporizing procedures and neglect the critical and fatal process of ongoing cellular destruction. Where supportive measures are not enough, orthotopic liver transplantation remains the only lifesaving procedure that may be offered. Unique to liver transplantation, the insurmountable barriers for the majority of patients are the severe global scarcity of donor organs. For those patients who receive a donor organ, the required lifetime of post-operative care and the strict regimen of immunosuppressive therapy carries inevitable highly unpleasant side effects of a personal risk such as opportunistic infections. Coupled with overwhelming post-operative care, the surgical procedure itself carries a high risk of untoward effects. The need for less biologically invasive procedures utilizing a Stem Cell like UC-MSCs is clear.
Rationale to utilize UC-MSCs for the treatment of Acute Liver Failure
This characteristic means that this Stem Cell type, specifically UC-MSCs, is useful in allogenic transplantation because of a lack of serious risk of transplant rejection and absence of problematic post-transplant immunosuppression. The immune response of the host is one of the most serious barriers in allogenic transplantation, and the use of these UC-MSCs has the potential to bypass this barrier. Furthermore, the Stem Cell populations have the potential for adaptive therapeutic response. They have the ability to adjust the amount of certain proteins that they release, based on the level of necrotic activity in the tissues that are inflamed. These cells provide adaptive and continuous support, which can improve areas of necrotic tissue in the liver, as well as promote regeneration of the liver tissue. Another advantage of the use of the cells is the lack of ethical issues. The cells are obtained from donated umbilical tissues, which are discarded after birth. The combination of these ethical advantages and the extensive therapeutic qualities to utilize UC-MSCs for the treatment of Acute Liver Failure.
Figure 1: Limitations of Current Conventional Treatments compared with UC-MSCs treatment in Acute Liver Failure
Future Trends within the Thai Medical Landscape
There is a global shift towards the application of regenerative medicine for the treatment of advanced liver conditions like Acute Liver Failure. The use of Stem Cell technologies within the Thai regenerative medicine model to treat advanced hepatic failure is a prime example of this shift. Thailand is in a prime position to pioneer these developments due to a combination of factors. Thailand has a great medical infrastructure with a lot of internationally accredited facilities and progressive Thai regulators who are open to new biotechnologies. These factors combine to create an ideal environment for the accelerated application of UC-MSCs cell based therapies. From an epidemiological standpoint, the population is in need of new liver therapeutics due to the high occurrence of infection causing Acute Liver Failure. The need for advanced liver therapeutics makes it a priority area for research. Additionally, by developing new Stem Cell therapeutics in Thailand, researchers will have the opportunity to create and optimize new UC-MSCs therapeutics based on regional and local factors. This targeted Stem Cell approach to regenerative hepatology utilizing UC-MSCs for Acute Liver Failure situates Thailand as a leader, cultivating local talent and drawing passive interest from the global medical community.