Zebrafish in Regenerative Medicine
Regenerative medicine is rapidly gaining huge strides in recent times due to evolving technology and techniques in current use. Zebrafish is one of the very few model animals that can regenerate its organs. In this article, we describe the use of Zebrafish in regenerative medicine and its various methods.
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Regenerative medicine has the potential to heal or replace tissues and organs damaged by age, disease, or trauma, as well as to normalize congenital defects.
The current therapy of transplantation of intact organs and tissues to treat organ and tissue failures and loss suffers from limited donor supply and often severe immune complications, but these obstacles may potentially be bypassed through the use of regenerative medicine strategies.
The field of regenerative medicine encompasses numerous strategies, including the use of materials and de novo generated cells, as well as various combinations thereof, to take the place of missing tissue, effectively replacing it both structurally and functionally, or to contribute to tissue healing.
The body’s innate healing response may also be leveraged to promote regeneration, although adult humans possess limited regenerative capacity in comparison with lower vertebrates.
Zebrafish Fin Regeneration:
Zebrafish has regeneration capability in its organs such as fins, central nervous system (CNS), heart, pancreas, liver, and kidney.
Regarding this given capacity, it is used for different models of injury for example in cardiovascular, neurological, and metabolic diseases.
Additionally, zebrafish is used as an animal model in personalized medicine for studying different diseases like cancers as avatars due to its beneficial advantages which are discussed in this review.
Organ Regeneration in Zebrafish:
This animal has a remarkable capacity of organ regeneration including fins, CNS, heart, pancreas, liver and kidney, some of which are introduced.
Unlike adult mammalian cardiac muscle, zebrafish have the ability of heart regeneration, indicating a potential way to decrease the mortality and morbidity of cardiac diseases.
There are two major components of heart regeneration: the proliferation of existing cardiomyocytes and an environment for stimulating muscle generation.
Accordingly, there are different injury models being used to stimulate heart regeneration in zebrafish such as cryoinjury and genetics.
Another surprising area in zebrafish is neural regeneration. Neuronal cell loss results in mental, motor, or visual impairment in humans while the capacity of regenerating neurons (in the brain, spinal cord, and retina) is found in zebrafish.
In order to direct retinal development, Muller glia are induced to yield multipotent neural progenitor cells which migrate to the damaged site and differentiate into the target cell type.
In the spinal cord, zebrafish can produce new axonal projections, neurons, and interneurons at the damaged region.
The axonal regeneration is based on radial glial cells that infiltrate the lesion site and proliferate, which is affected by fibroblast growth factor (FGF) signaling.
Pancreas & Liver Regeneration:
The pancreas, as a major regulatory organ, has a limited ability of regeneration and its response to injury is usually through inflammation and repair mechanisms which result in diabetes and insulin dependence.
On the contrary, the pancreas in adult zebrafish can recover after chemical treatment or surgery (pancreatectomy) without the help of insulin therapy.
Histological analysis revealed that dividing insulin-positive β cells are seen in both islets and pancreatic ducts, indicating that they might be a source of β cell progenitors.
In addition, Centro-acinar cells may differentiate or α cells convert into β cells.
Likewise, the liver can regenerate following hepatectomy, drug-induced hepatotoxicity, and hepatocyte ablation in adult zebrafish.
All in all, since humans are rather incapable of regenerating some tissues and organs such as cardiac muscle and the CNS, there are two main options to overcome this challenge: application of an exogenous tissue or cell source or stimulation of the endogenous cells.
Accordingly, to study the methodology of activating the endogenous cells, zebrafish is an appropriate animal model.
Moreover, it has contributed to metabolic diseases research including pathologic conditions in the pancreas and liver by making the identification of signals and regeneration mechanisms easier. Therefore, it can be said that the emerging field of zebrafish can be used for therapeutic approaches.