Development of Human Brain Organoids, The Formation of Neural Circuits and Relationship with Neurodevelopmental Diseases

Öz

İnsan kaynaklı pluripotent kök hücreleri (hiPSC'ler) ve insan embriyonik kök hücreleri (hESC'ler), kültür ortamında kendilerini sonsuza kadar yenileyebilen ve hemen her tür insan hücresine dönüşme potansiyeline sahip iki tür insan pluripotent kök hücre olarak bilinmektedir. Beyin organoidleri, pluripotent kök hücrelerden gelen, bilim dünyası için son derece değerli bir kaynak oluşturmaktadır. İnsan beyinlerinin patofizyolojisini, doku mühendisliğini ve gelişim süreçlerini araştırmak için kullanılmakta olup, doğal büyüme mekanizmaları taklit edebilme özellikleriyle dikkat çekerler. Özellikle, insan embriyonik kök hücrelerinden elde edilen insan kortikal organoidleri (hCO'lar), insan beyninin gelişimi ve bozukluklarını 3B dokuda ayrıntılı incelemek için mükemmel bir model sunmaktadır. Ancak, bu alandaki ilerlemelere rağmen, hala bir dizi cevapsız soru vardır. Bunlar arasında işlevsiz kan atardamarları, mikroglianın yetersiz gelişimi ve korteksin altı farklı katmanının tam anlamıyla oluşturulamaması bu modellerin sınırlılıkları arasında yer almaktadır. Bununla birlikte, modern hCO'larda mikro damarlanmanın olmaması, hCO'ların iç bölgelerine ulaşabilen oksijen ve besin miktarını sınırlamaktadır. Bu inceleme kapsamında, beyin organoidlerinin oluşturulma yöntemleri, bu süreçte yaşanan zorluklar ele alınmaktadır. Ayrıca, beyin organoidlerinin geliştirilmesi ve ilgili son yenilikler ve bu teknolojinin erken beyin gelişimi ile nörolojik bozuklukların araştırılmasındaki potansiyel kullanımları üzerine güncel bilgiler sunulmaktadır.

Anahtar Kelimeler

• Kök hücre
• Beyin
• Doku Mühendisliği
• Rejeneratif Tıp
• Beyin Organoidleri

Development of Human Brain Organoids, The Formation of Neural Circuits and Relationship with Neurodevelopmental Diseases

Öz

Human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) are known as two types of human pluripotent stem cells (hPSCs) capable of self-renewing indefinitely in culture and differentiating into almost any type of human cell. Brain organoids, derived from pluripotent stem cells, serve as an extremely valuable resource for the scientific community. They are utilized to study the pathophysiology, tissue engineering, and development processes of human brains, distinguished by their ability to mimic natural growth mechanisms. In particular, human cortical organoids (hCOs) derived from human embryonic stem cells provide an excellent model for detailed three-dimensional investigations of human brain development and disorders. Despite advancements in this field, several unresolved issues persist. These limitations include non-functional blood arteries, restricted development of microglia, and the incomplete formation of the six distinct layers of the cortex. Additionally, the lack of microvascularization in modern hCOs limits the amount of oxygen and nutrients that can reach the inner regions of the hCOs. This review addresses the methods used for creating brain organoids and examines the challenges encountered in these processes. Furthermore, it highlights the latest advancements in the development of brain organoids and provides updated insights into their potential applications in studying early brain development and neurological disorders.

Anahtar Kelimeler

• Stem cell
• Brain
• Tissue Engineering
• Regenerative Medicine
• Brain Organoids

Kaynakça

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