WINSTON-SALEM, NC, Feb. 13, 2018 – Scientists at Wake Forest Institute for Regenerative Medicine (WFIRM) have developed the most sophisticated mini-livers to date. These organoids can potentially help scientists better understand certain congenital liver diseases as well as speed up efforts to create liver tissue in the lab for transplantation into patients.
“This model better mimics fetal development and function of the human liver,” said Shay Soker, Ph.D., professor of regenerative medicine at WFIRM, which is part of Wake Forest Baptist Medical Center. “We expect these organoids to advance our understanding of how liver diseases – especially congenital diseases — start and progress so improved treatments can be developed.”
Soker was lead researcher on the study, which is reported in Hepatology.
The creation of living mini-organs is a relatively new area of science with the potential to replace animal models that are not always accurate. The liver organoids, made with human cells, are less than one-third inch in diameter. While scientists have already created liver organoids to screen new drugs for liver toxicity, the livers developed in this research represent several “firsts” in the quest to build a functional model of human liver development.
To make the organoids, scientists allow fetal liver progenitor cells, an immature cell that is destined to become a specialized liver cell, to self-assemble on a small disc. The discs are made of ferret liver that has been processed to remove all of the animal’s cells. The resulting organoids, which assemble within two to three weeks, are the first to model actual human liver development.
The research is significant in two ways. First, the scientists showed that these organoids generated hepatocytes, the main functional cells of the liver. This achievement represents a milestone in work to create truly functional bioengineered liver tissue for transplantation into patients.
Second, while other scientists have shown that lab-grown livers can generate bile ducts, this is the first study to show the stepwise maturation of bile ducts exactly as can be observed in the human fetal liver. Bile ducts carry bile, a fluid that is secreted by the liver and collected in the gall bladder to digest fats. This model of bile ductal development can potentially be used to study the hereditary disease biliary atresia that occurs in infants. With this disease, bile drainage is impaired, making it fatal in the more severe cases.
“Altogether, the team has created a laboratory model of human liver development and disease that will help advance our understanding about bile duct formation,” said first co-author Pedro Baptista, Pharm.D., Ph.D., who was with WFIRM at the time of the research.
“This is a big step toward advancing the bioengineering of functional livers and bile ducts and we look forward to using it in a variety of ways to mprove human health,” said first co-author Dipen Vyas, Ph.D., also at WFIRM at the time of the research.
The research was sponsored by the National Institutes of Health and the state of North Carolina.
Co authors were Dipen Vyas, Ph.D., Biorg Inc., and Pedro Baptista, Pharm.D., Ph.D., Health Research Institute of Aragon, Spain; Matthew Brovold, B.Sc., Brandon Gaston, B.Sc., Chris Booth, B.Sc., Michael Samuel, B.Sc., and Anthony Atala, M.D., Wake Forest Baptist; and Emma Moran, Ph. D., Cook Research Inc.
SOURCE: Wake Forest Baptist Medical Center
WINSTON-SALEM, NC, Februari 13, 2018 - Wanasayansi katika Taasisi ya Wake Forest ya Tiba ya Regenerative (WFIRM) wametengeneza ini ndogo za kisasa zaidi hadi sasa. Vifaa hivyo vinaweza kusaidia wanasayansi kuelewa vizuri magonjwa fulani ya ini na pia kuharakisha juhudi za kutengeneza tishu ya ini katika maabara ili kuipandikiza kwa wagonjwa. "Mfano huu unaiga vizuri maendeleo ya kiinitete na kazi ya ini la binadamu, "alisema Shay Soker, Ph.D., profesa wa dawa ya kurudisha upya katika WFIRM, ambayo ni sehemu ya Kituo cha Matibabu cha Wake Forest Baptist. "Tunatarajia organoids hizi kuendeleza uelewa wetu wa jinsi magonjwa ya ini - hasa magonjwa ya kuzaliwa - kuanza na maendeleo hivyo matibabu bora inaweza kuwa maendeleo. ""Soker alikuwa mtafiti wa kuongoza juu ya utafiti, ambayo inaripotiwa katika Hepatology." Uundaji wa viungo vidogo vya uhai ni uwanja mpya wa sayansi na uwezekano wa kuchukua nafasi ya mifano ya wanyama ambayo sio sahihi kila wakati. Viungo vya ini, vilivyotengenezwa kwa chembe za kibinadamu, vina kipenyo cha chini ya inchi moja ya tatu. Wakati wanasayansi tayari wameunda organoids ya ini ili kuchunguza dawa mpya kwa sumu ya ini, ini zilizotengenezwa katika utafiti huu zinawakilisha "kwanza" kadhaa katika jitihada ya kujenga mfano wa kazi ya maendeleo ya ini ya binadamu. Ili kutengeneza organoids, wanasayansi huruhusu chembe za kiini za kiinitete, chembe zisizokua ambazo zimekusudiwa kuwa chembe za kiini maalumu, kujikusanya kwenye diski ndogo. Diski hizo zimetengenezwa kwa ini la mbweha ambalo limetengenezwa ili kuondoa chembe zote za mnyama huyo. Vipengele hivyo vinavyoweza kuunganishwa kwa muda wa majuma mawili au matatu, ni vya kwanza kuiga ukuzi halisi wa ini la binadamu. Utafiti huo ni muhimu kwa njia mbili. Kwanza, wanasayansi walionyesha kwamba organoidi hizo zilitokeza chembe za ini, chembe kuu za ini. Mafanikio haya yanawakilisha hatua muhimu katika kazi ya kuunda tishu ya ini ya uhandisi wa kibiolojia inayofanya kazi kweli kwa ajili ya kupandikiza kwa wagonjwa. "Wanasayansi wengine wameonyesha kwamba ini lililopandwa katika maabara linaweza kutokeza mifereji ya bile, lakini hii ni utafiti wa kwanza kuonyesha kukomaa kwa hatua ya mifereji ya bile kama inavyoonekana katika ini ya mtoto.""" Mifereji ya bile hubeba bile, umajimaji unaotokezwa na ini na kukusanywa katika kibofu cha mkojo ili kumeng'enya mafuta. Mfano huu wa maendeleo ya ductal bile inaweza uwezekano wa kutumika kujifunza ugonjwa wa urithi atresia biliary ambayo hutokea katika watoto wachanga. Ugonjwa huo husababisha upungufu wa maji ya ndoo, na katika visa vikali zaidi, ugonjwa huo hufa. "Kwa pamoja, timu hiyo imeunda mfano wa maabara ya maendeleo ya ini la binadamu na ugonjwa ambao utasaidia kuendeleza uelewa wetu kuhusu uundaji wa njia ya bile, "alisema mwandishi wa kwanza Pedro Baptista, Pharm.D., Ph.D., ambaye alikuwa na WFIRM wakati wa utafiti. """ "Hii ni hatua kubwa kuelekea kuendeleza uhandisi wa kibiolojia wa ini na mifereji ya bile na tunatarajia kuitumia kwa njia mbalimbali ili kuboresha afya ya binadamu,"" alisema mwandishi mwenza wa kwanza Dipen Vyas, Ph.D., pia katika WFIRM wakati wa utafiti. """ Utafiti huo ulifadhiliwa na Taasisi za Kitaifa za Afya na jimbo la North Carolina. "Wanafunzi wa ""Diploma de la Vida"" na ""Diploma de la Vida"" na ""Diploma de la Vida"" na ""Diploma de la Vida"" na ""Diploma de la Vida"" na ""Diploma de la Vida"" na ""Diploma de la Vida"" na ""Diploma de la Vida"" na ""Diploma de la Vida"" na ""Diploma de la Vida"" na ""Diploma de la Vida"" na ""Diploma de la Vida.""" D., Cook Utafiti Inc. "Kifaa cha ""Wake Forest Baptist Medical Center"""