In vivo and ex vivo methods of growing a liver bud
through tissue connection.
The new cellular and molecular data uncovered in the current study will be "exploited in the future to further improve liver bud
organoids" and "precisely recapitulate differentiation of all cell types" in fetal human development, the authors write.
The septum transversum mesoderm is known to support the growth of the liver bud
Abnormal migration of some portion of hepatic diverticulum or the liver bud
to other tissues is believed to be the cause of ectopic liver.
During embryonic development, BMP4 plays an important role in liver bud
formation (Duncan and Watt 2001).
"The cells self-assembled and organized into a liver bud
," says Ken Zaret, a developmental biologist at the University of Pennsylvania in Philadelphia.
"We just simply mixed three cell types, including the human iPS-derived hepatic progenitors, and found that they unexpectedly self-organise to form a three dimensional liver bud
," said Prof Takebe.
However, to their surprise the cells started to organise themselves and started curling to form a liver bud
Two days later, the cell assortment had self-organised to form a three-dimensional "liver bud
"-a 5mm-wide chunk of tissue that performed basic liver functions.
Five pairs of endoderm-lined pharyngeal pouches give rise to the middle ear cavity, auditory tube, tympanic membrane (from the first pair), palatine tonsils (from the second pair), thymus and lower parathyroid glands (from the third pair), upper parathyroid glands (from the fourth pair), and parafollicular cells of the thyroid gland The subsequent foregut extends to the bottom of the liver bud
. The respiratory system, esophagus, stomach, proximal part of the duodenum, liver, pancreas, and bile duct develop from this part.
Several theories have been proposed to explain the development of ectopic liver at different sites: development of an accessory lobe of the liver with atrophy or regression of the original connection to the main liver, (4) migration or displacement of a portion of the cranial part (Pars hepatica) of the liver bud
to other sites, (6) dorsal budding of hepatic tissue before the closing of the pleuroperitoneal canal (may explain how EL develops in the thoracic cavity such as esophagus, pericardium, intra pleural or extra pleural), (7) trapping of hepatocyte-destined mesenchyma in different areas (8) and entrapment of nests of cells in the region of the foregut following closure of the diaphragm or umbilical ring.
"Because we can now overcome these obstacles to generate highly functional, three-dimensional liver buds
, our production process comes very close to complying with clinical-grade standards," lead researcher Takanori Takebe said.