분자유전학실험실 (단국대학교 분자생물학과)



 이성욱 ( 2017-07-25 19:37:17 , Hit : 780
 Engineered Human Liver Tissue Grows in Mice

http://www.the-scientist.com/?articles.view/articleNo/49927/title/Engineered-Human-Liver-Tissue-Grows-in-Mice/&utm_campaign=NEWSLETTER_TS_The-Scientist-Daily_2016&utm_source=hs_email&utm_medium=email&utm_content=54452440&_hsenc=p2ANqtz-_KscaPcpT2t-c46Ez_e3vHGG6gLXoY19Z_sLJFXvzoshHdfOhaO8MMv70atzQiyJiHDT7U-zsHa_5kzJOe10dGjM7emg&_hsmi=54452440

The Scientist »
News & Opinion »
Daily News

Tissue “seeds” made up of three cell types and patterned onto a scaffold develop into complex structures with some organ function, researchers show.

By Anna Azvolinsky | July 19, 2017

Engineering human livers is a lofty goal. Human liver cells, hepatocytes, are particularly difficult to grow in the laboratory as they lose liver functions quickly in a dish. Now, in a study published today (July 19) in Science Translational Medicine, researchers show that a “seed” of human hepatocytes and supporting cells assembled and patterned within a scaffold can grow out to 50 times its original size when implanted into mice.

These engineered livers, which begin to resemble the natural structure of the organ, offer an approach to study organ development and as a potential strategy for organ engineering.

“What blew my mind is that when we implant these tissues into a mouse with liver injury, the tissue seeds just blossom,” says study author Kelly Stevens, who conducted the experiments as a postdoc in Sangeeta Bhatia’s lab at MIT and now runs her own bioengineering lab at the University of Washington. “Nature takes over and self-assembles a structure that looks like a human liver and has many liver-associated functions.”

“This is a very exciting approach and another demonstration that we can build a basic liver unit using three basic cell types,” says Tammy Chang, an assistant professor of surgery at the University of California, San Francisco, who studies liver tissue regeneration and was not involved in the latest work.

In 2011, Bhatia's lab showed that human liver-cell aggregates could be grown in mice. She and her colleagues assembled human hepatocytes and supportive stromal cells within a polymer scaffold, demonstrating that this dime-size artificial human liver tissue could grow stably for weeks in immune-compromised mice that had their own normal livers. The liver implant, the researchers found, fused with the mouse circulatory system and received blood to perform a few liver functions.

See “The Organist”

In the new work, the lab wanted to expand the size of the human liver graft beyond the 1 million cells used in the prior model. The team assembled different geometries of human primary hepatocytes, human umbilical vein endothelial cells, and fibroblasts, placed them within a degradable hydrogel, and implanted the tissue seed into a fat pad within a liver-injury mouse model.

To recapitulate liver damage, the animals are missing a key amino acid metabolism gene that results in toxic metabolite build up and progressive liver failure, which can be rescued by a drug used to treat individuals with a similar genetic disorder. Stevens says her group chose this model because it they expected it to foster the liver seeds’ growth. “The hypothesis is that mouse liver injury will produce factors that will travel through the blood stream and tell the human liver tissue to regenerate,” explains Stevens.  

The team found that the human liver tissue grew less in animals that were continuously treated with the drug compared to animals that were given intermittent cycles of the small molecule.

The human liver seed tissue grew best, the researchers found, when they assembled endothelial cells into rope-like structures on top of the hepatocytes, rather than when the tissue was a spherical aggregate of all three cell types. The patterned tissue formed new structures in vivo, including ones that resembled bile ducts, and contained pockets of red blood cells, suggesting the presence of vascular structures within the tissue. The organ-like structures also produced appropriate human proteins such as albumin and transferrin.

“These results clearly suggest that the geometric design of a transplant graft is an important consideration for [organ engineering], at least for an ectopic implantation approach,” Takanori Takabe, whose lab at Yokohama City University in Japan is developing organs from stem cells and who was not part of the study, writes in an email to The Scientist.

See “Orchestrating Organoids”

Researchers have been using stem cells to make organoids in a dish, miniature three-dimensional cell clusters, which are used to study the biology and formation of organs.

“At the moment, it is a great and unique research tool to understand liver growth,” Eric Lagasse, who works on stem cells and organogenesis at the University of Pittsburgh and was not involved in the study, writes in an email to The Scientist.

For Chang, a major question is what is special about this liver injury model. “The robust growth of the liver tissue here may be unique to this form of livery injury and it would be interesting now to understand the factors that promote regeneration and growth of these liver tissue aggregates,” she says.

And, of course, there’s the question of utility in humans, notes Stevens. “Could we eventually get this to the level where it can be transplanted into patients to provide them with some liver function?”

K. R. Stevens et al., “In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease,” Science Translational Medicine, doi:10.1126/scitranslmed.aah5505, 2017.  










1107   Dynamic view of the MS genome  이성욱 2010/05/01 2717
1106   Early-Earth cells modeled to show how first life forms might have packaged RNA  이성욱 2012/10/16 2515
1105   Editas Expands CRISPR Capabilities through New Technology Licensing  이성욱 2016/12/22 820
1104   Efficient Process Using microRNA Converts Human Skin Cells Into Neurons  이성욱 2011/07/19 2238
1103   Electronics Giant Samsung Makes First Big Biotech Play  이성욱 2013/02/22 3165
1102   EMA panel recommends approval of DAA regimen for patients with HCV  이성욱 2014/11/26 1282
1101   Embryonic stem cells improve vision for two women  이성욱 2012/01/25 2336
  Engineered Human Liver Tissue Grows in Mice  이성욱 2017/07/25 780
1099   Engineered Viruses Selectively Kill Cancer Cells  이성욱 2011/09/02 2444
1098   Engineering Better Immune Cells  이성욱 2010/05/06 2700
1097   EU, 2번째 유전자치료제 ‘스트림벨리스’ 승인  이성욱 2016/09/05 1146
1096   European regulators back first gene therapy drug  이성욱 2012/07/24 2669
1095   Exosomes Linked to Cancer Spread from Chemoresistant Tumors in Mice  이성욱 2019/01/15 778
1094   Expanding the reach of gene editing with a new CRISPR enzyme  이성욱 2018/10/26 399
1093   Experimental Hepatitis C Drug Shows Promise for Preventing Recurrence in Liver Transplant Patients  이성욱 2013/11/06 2134
1092   Experts find rogue stem cells in liver cancer  이성욱 2011/07/09 2570
1091   Fathers Can Pass Mitochondrial DNA to Children  이성욱 2018/12/26 794
1090   FDA approves 9-valent HPV vaccine for certain cancers  이성욱 2014/12/12 1142
1089   FDA Approves First Gene Therapy for Inherited Disease  이성욱 2017/12/22 512
1088   FDA Approves Gilead CAR-T Therapy Yescarta, Plans Regenerative Medicine Policy 'Soon'  이성욱 2017/10/20 608

[1][2][3][4][5][6][7][8] 9 [10]..[64] [다음 10개]
 

Copyright 1999-2021 Zeroboard / skin by ROBIN