مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Promising Approaches in Modeling and Treating Alzheimer’s Disease Using Stem Cell and Bioprinting Technologies
Promising Approaches in Modeling and Treating Alzheimer’s Disease Using Stem Cell and Bioprinting Technologies
Elahe Yazdani,1Hengameh Dortaj,2,*
1. Mashhad University of Medical Sciences 2. Mashhad University of Medical Sciences
Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that results in a gradual deterioration of cognitive function, such as memory, language, and behavior. According to the Alzheimer's Association, Alzheimer's Disease (AD) is the primary cause of dementia, representing about 60–80% of all instances. Global predictions suggest a significant rise in the number of individuals affected by this condition, with estimates indicating that by 2050, about 139 million people will be impacted, with more than two-thirds expected to be women. Neuropathological hallmarks of the disease include the deposition of extracellular amyloid-beta (Aβ) plaques and the formation of intracellular neurofibrillary tangles of hyperphosphorylated tau protein. Although some known genetic mutations confer an increased risk for developing AD, current treatment options provide only symptomatic relief and do not impact disease progression. In recent years, the development of physiologically relevant in vitro models for AD is important to give more insights into its biological mechanisms and new treatment options. Currently, the existing pre-clinical models for AD encompass two-dimensional cell culture systems, various animal models, and tissues obtained from human cadavers. Nonetheless, the shortcomings and constraints observed in clinical trials of these drugs highlight the necessity for more physiologically relevant models of AD.
Methods: Bioprinting, as a type of additive manufacturing, combines cells with biomaterials to create three-dimensional structures that mimic in vivo tissue. The 3D-printed neural tissues could then be used for screening potential drug targets for Alzheimer’s disease as an alternative to expensive preclinical animal testing. Stem cells exhibit enhanced properties of self-renewal, proliferation, differentiation, and recombination due to advancements in stem cell technology, enabling the conversion of these cells into various types of neurons and glial cells within the central nervous system. Stem cells have already demonstrated their utility in developing functional models of neural tissue. Neural stem cells (NSCs) possess multipotent capabilities and differentiate into the various cell types present in the neurological system. By contrast, pluripotent cells, such as embryonic stem cells and induced pluripotent stem cells (iPSCs), possess the ability to differentiate into almost all cell types found in the body. Numerous research efforts have been conducted with various 3D models of organoids and post-mortem tissues to utilize human induced pluripotent stem cells(hiPSCs) in the modeling of AD. Using post-mortem human brain tissue and hiPSC-derived cortical neurons, increased BMI1 expression was found to reduce tau accumulation in Alzheimer’s disease models.
Results: Brain organoids generated from patient-derived hiPSCs exhibited characteristic features of AD pathology, including amyloid beta aggregation and the formation of hyperphosphorylated tau protein. Treatment with β- and γ-secretase inhibitors led to a noticeable reduction in both amyloid and tau-related abnormalities. Neurons originating from stem cells can integrate into the established neural networks of the host brain. Furthermore, stem cell transplantation appears to elevate acetylcholine levels, consequently improving cognition and memory in animal models. Additionally, stem cells release neurotrophic factors that play a crucial role in modulating neuroplasticity and neurogenesis.
Conclusion: The combination of stem cell technology and 3D bioprinting signifies a hopeful strategy for creating physiologically relevant models of Alzheimer's disease. These models serve as important platforms for drug screening and mechanistic investigations, delivering insights that conventional animal models might not provide. Although there are challenges to overcome, therapies based on stem cells possess considerable promise for the advancement of safe and effective clinical treatments for Alzheimer's disease.