There are severe worldwide effects caused by chronic genetic blood disorders. Patients suffer from fatigue, chronic pain, and irregular bone growth, and their organs are gradually damaged. Patients experience a drastic decrease in quality of life and require constant medical treatment. Finding a biological cure is always a concern, and current treatment options only address symptoms of the disease, leaving the damaged blood and organs untreated. Regenerative medicine and UC-MSCs provide safe options to treat the root cause of β-thalassemia, and a change in treatment paradigms for this genetic disease is long overdue. β-thalassemia patients require Stem Cell therapy to provide new, healthy Stem Cells and change the patients’ pathological course.
Biological Mechanism
A basic understanding of the biological systems of UC-MSCs shows how Stem Cells work. When UC-MSCs are directly infused into β-thalassemia patients, the Stem Cells will migrate to the bone marrow. However, unlike hematopoietic Stem Cell differentiation, UC-MSCs will migrate and stay in the marrow to provide support by communicating with blood cells through paracrine signaling and releasing extracellular vesicles. By providing a supportive environment for erythropoiesis, UC-MSCs also suppress inflammation and immune responses that cause damage to developing blood cells. By aiding erythropoiesis, this will also serve as a UC-MSCs support niche and a marrow microenvironment. Therefore, the characteristic severe ineffective erythropoiesis of β-thalassemia is sharply reduced.
Traditional Treatment Limitations
The management of this severe form of anemia has, until recently, involved frequent blood transfusions that provide temporary relief from systemic hypoxia. This is not without serious complications. The body does not have a mechanism to excrete excessive transfused red blood cells, resulting in an iron overload. Excess iron is deposited in the heart, liver, other endocrine organs, and tissues. The toxicity of iron that accumulates in the organs and tissues of patients with β-thalassemia, requires the administration of aggressive iron chelation therapy. Chelation therapy binds metals and facilitates their elimination from the body. Chelation therapy, which must be continued throughout the patients’ life, is also associated with severe side effects such as prolonged vomiting and an increased risk of developing chronic kidney disease, and ultimately a reduced transfusion compliance. It must also be mentioned that the continual demand for transfused blood is a significant a burden on the publicly funded health care system.
Rationale for Alternative Therapy
A new therapy must forgo the use allogenic blood transfusion and be a biological agent that is capable of fundamentally repairing tissues. This is why UC-MSCs Stem Cell therapy, with their powerful capacities for immunomodulation, may be particularly suitable. β-thalassemia is due to a malfunction of the immune system that causes destruction of immature erythrocytes. UC-MSCs have the unique property of immunomodulation and provide a powerful means of halting this destructive process. They selectively secrete transforming growth factor-β and other regulatory proteins that inhibit the proliferation of effector T-cells while enhancing the proliferation of T-reg cells. This immune tolerance thereby greatly reduces destruction of immature erythrocytes.
Additionally, this cell type releases factors critical to promote proliferation and maturation of erythrocytes. Unlike other transplantations that mandate rigorous antigen compatibility, this tissue provides a unique, low immunogenicity profile. They completely lack class II major histocompatibility complex molecules. This enables the allogenic application of UC-MSCs, without provoking a severe graft-versus-host reaction, rendering it a truly accessible resource.
Figure 1: Comparing Traditional treatment and UC-MSCs therapy in β-thalassemia
The Future Trends in Thailand
The prevalence of genetic hemoglobinopathies is especially high in Southeast Asia. The situation is even worse in Thailand, following the drift of some genetic markers in population history. With a high concentration of disorder risk in the population, considering the therapies that stem from the innovative and costly biomedical imports is no longer sustainable for the public health system. Thai research institutes have begun to focus on more active clinical research to improve the regenerative health systems in the country. Given the amount of tissue donation, especially in maternity wards, Thai researchers have more than enough to draw on. The efforts aimed at the establishment of local manufacture of Stem Cells are more than welcomed, as they authorize the novel biotechnology and genetic therapies. The cellular biotechnology are in the stage of integration in the healthcare system. It is aimed to make Thailand an important and a regional point for the therapies of β-thalassemia.
Conclusion
In order to find a proper treatment for complex genetic blood disorders, it is insufficient to focus only on symptomatic therapies. β-thalassemia and its related dysregulations in the body are especially complex. The ultimate goal of the long-term sustainable therapies may be to restore normal physiological functions of MSCs. This may be a possibility to rely on the regenerative potential of umbilical cord blood. This population of Stem Cells inhibits inefficient erythropoiesis by modifying the microenvironment of the bone marrow. They offer a great advantage over traditional blood transfusion protocols by preventing organ failure due to iron toxicity. The low degree of immunogenicity also adds to the prospect of their therapeutic universality. With the eastern and southeastern parts of Asia the most advanced in their development, patients with this condition can expect Stem Cells to provide therapy in the near future. Current and continuing developments in biological science provide assurance that the Direct and indirect effects of β-thalassemia will soon be consigned to a regrettable chapter of history.