{"id":10615,"date":"2026-04-20T20:37:23","date_gmt":"2026-04-20T20:37:23","guid":{"rendered":"https:\/\/globalnewstoday.uk\/index.php\/2026\/04\/20\/synthetic-biology-and-tissue-engineering-grow-liver-tissue-in-body-genetic-engineering-and-biotechnology-news\/"},"modified":"2026-04-20T20:37:23","modified_gmt":"2026-04-20T20:37:23","slug":"synthetic-biology-and-tissue-engineering-grow-liver-tissue-in-body-genetic-engineering-and-biotechnology-news","status":"publish","type":"post","link":"https:\/\/globalnewstoday.uk\/index.php\/2026\/04\/20\/synthetic-biology-and-tissue-engineering-grow-liver-tissue-in-body-genetic-engineering-and-biotechnology-news\/","title":{"rendered":"Synthetic Biology and Tissue Engineering Grow Liver Tissue In\u2011Body – Genetic Engineering and Biotechnology News"},"content":{"rendered":"

Damage to the liver in patients developing end-stage liver disease has become too severe for the organ\u2019s normally extraordinary regenerative capacity to repair or compensate for that damage. Once this point of no return has been reached the only option is an organ transplant. However, donor livers are in high demand and very limited supply.
Ambitious efforts are on the way that eventually could enable the engineering of entire implantable liver organs. However, the maximum size of laboratory-engineered liver constructs remains limited and cannot yet provide therapeutic benefits for patients. A research team at the\u00a0Wyss Institute at Harvard University,\u00a0Boston University, and\u00a0MIT\u00a0has now approached this important problem from a different angle.
\u201cWe asked if it would be possible to first implant a small-scale liver construct and then drive it to expand in the body following its engraftment,\u201d said Christopher Chen, MD, PhD, a Wyss Institute core faculty member and the William Fairfield Warren Distinguished professor of biomedical engineering and director of the Biological Design Center at Boston University. \u201cA sufficiently grown, functional \u2018satellite liver\u2019 could immediately relieve the metabolic burden in a damaged liver and help bridge the time until a transplant becomes available.\u201d
Chen co-led the research together with associate faculty member Sangeeta Bhatia, MD, PhD, who is the John J. and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at the Koch Institute for Integrative Cancer Research at MIT, and a Howard Hughes Medical Institute investigator. Chen is also a leader of the Wyss Institute\u2019s 3D Organ Engineering Initiative, and team lead of the recently awarded ARPA-H PRINT-supported ImPLANT project, which focuses on whole organ liver engineering at the Wyss and collaborating institutions.
The project, spearheaded by Amy Stoddard, PhD, (MIT \u201925),\u00a0who developed the approach in her doctoral research and then as a postdoctoral fellow,\u00a0integrates tissue engineering and synthetic biology tools in a genetic strategy the team has named \u201cbioengineered on-demand outgrowth\u00a0via\u00a0synthetic biology triggering,\u201d or BOOST. By specifically rewiring the gene expression of primary liver hepatocytes and supportive fibroblast cells, the scientists were able to effectively switch on a tissue growth program in small, engineered liver constructs after their implantation into mice.
\u201cUsing engineered liver tissue as a proof-of-concept application, we integrated synthetic biology and tissue engineering tools to build liver tissues that can be expanded on-demand after implantation in vivo<\/em>,\u201d the team reported in their published paper in Science Advances<\/em>, which is titled \u201cSynthetic control of implanted engineered liver tissue growth<\/a>.\u201d In the paper they concluded \u201cIn this study, we define the first steps toward an unconventional approach to cell therapy scale-up: engineering a small construct and then inducing it to grow in situ<\/em> \u2026 \u201cThis strategy, which we have named BOOST, could provide several key advantages, including circumventing the need for large quantities of cellular raw materials and bypassing the formidable challenge of generating a rapidly perfusable construct that can survive the engraftment period.\u201d
The authors wrote, \u201cOrgan transplant is currently the only curative treatment for patients with end-stage organ failure, yet this therapy is inaccessible to many due to the paucity of organs available for transplant.\u201d And while significant progress has been made in the field of engineering tissue-based cell therapies that could represent alternatives, or bridges to transplant, they acknowledge, \u201c\u2026 scaling of these constructs to sizes of therapeutic relevance remains a barrier to clinical translation.\u201d
In order to address current challenges associated with fabrication, Chen and colleagues looked at the problem from different angle, asking whether it would be possible to first implant a small-scale construct and then trigger it to expand in situ<\/em>, after its engraftment into the host.
To be able to induce growth of an implanted small liver constructs\u00a0in situ<\/em>\u00a0within a recipient\u2019s body the researchers first needed to identify the relevant cues that would allow them to do so.\u00a0\u201cA key first step toward this method of in situ<\/em> scale-up would be the successful control of cellular growth within the engineered construct after engraftment,\u201d they wrote. Since liver growth is known to be regulated by soluble growth factors (GFs), Stoddard screened a collection of candidate factors to identify those that, when added to cultured human primary hepatocyte cells (HEPs), had the strongest growth-inducing effects.<\/p>\n

\"The
The genetic \u201cBOOST\u201d strategy integrates tissue engineering and synthetic biology tools to enable on-demand liver growth inside the body. By specifically rewiring the gene expression of primary liver hepatocytes and supportive fibroblast cells, a tissue growth program is switched on in a small, engineered liver construct after its implantation into recipients and upon addition of an inducing agent (shown as a pill). As a result, the hepatocytes in the construct start and continue to proliferate until a desired construct size has been reached and the inducing signal is not provided anymore. In mice, BOOST resulted in robust and healthy liver growth. [Wyss Institute at Harvard University]<\/figcaption><\/figure>\n

\u201cWe ended up with a set of four growth factors, HGF, TGFa, WNT2 and RSPO3, that potently induced sparsely scattered HEPs to grow in the culture dish,\u201d said Stoddard. \u201cBut when we tested whether they could do the same in 3D liver tissues consisting of densely packed HEPs and fibroblasts, they turned out to be ineffective. This led us to hypothesize that there must be an additional mechanism at work in human HEPs that inhibits cell proliferation in high-density conditions.\u201d
The team homed in on a protein, YAP, that senses mechanical signals, and which was known to move from cells\u2019 cytosol to their nucleus in low-density conditions to help express genes involved in cell proliferation. However, in high-density conditions when cells are compressed, YAP is degraded in the cytosol, which prevents the activation of those target genes and restricts proliferation.
\u201cImportantly, when we overexpressed a non-degradable version of YAP in HEPs, which also reaches the nucleus in high-density conditions to partake in gene regulation, we successfully overrode this density checkpoint in HEPs,\u201d Stoddard said. \u201cInterestingly, we found that HEPs needed to be stimulated with both YAP and GFs in order to grow in densely packed 3D liver tissues.\u201d
Toward the goal of safely inducing and controlling HEP proliferation in a living organism, and eventually human patients, the researchers deployed synthetic biology tools to locally install control of these signaling pathways in HEPs and fibroblast cells within the engineered 3D liver tissues themselves. \u201cWe set out to engineer a synthetic biology toolkit capable of locally modulating growth factor and YAP signaling within engineered liver tissue, enabling on-demand control of proliferation even after implantation,\u201d they noted.
The team engineered fibroblast cell lines that each secreted one of the four GFs, and HEPs that expressed the non-degradable YAP protein. And they made the expression of all proteins doxycycline (DOX)-inducible. They determined in time course experiments that a continuous seven-day treatment with DOX led 3D liver tissue composed of engineered cells to robustly expand in size and cell numbers in the culture dish. On DOX removal the HEPs reverted back to a non-proliferating state.
However, Stoddard noted, \u201c\u2026 when we compared the gene expression of single cells in BOOST-engineered, DOX-induced 3D liver tissue to that of cells in non-engineered or BOOST-engineered, non-induced 3D liver tissue, we noticed that the expansion came with a trade-off: high proliferation rates went hand in hand with a less functional HEP state. While we believe this is a natural trade-off seen in a wide variety of biological settings, we hope to be able to address this in the future, recognizing that the liver also has native re-functionalization signals to harness.\u201d
The litmus test for BOOST-engineered growth in 3D liver tissues was to see whether they would similarly expand following their implantation into living mice that were systemically treated with DOX for the same seven-day duration. Experiments showed that the implanted tissue exhibited a striking 500% increase in proliferation with a doubling of the engineered HEPs alone, and was vascularized to accommodate the metabolic demands of the expanded tissue. The tissue implants were also well tolerated by the mice, with no signs of fibrosis due to invading immune cells and fibroblast inflammation, or of tumor growth.
\u201cThese results were particularly exciting to us,\u201d said Stoddard. \u201cPrior to our work, injury to the host liver has always been required to trigger hepatocyte engraftment and proliferation. Here we were able to relieve this dependence, and trigger on-demand growth of implanted liver tissue in a completely healthy host.”
In the future, the team will explore the capacity of BOOSTed liver tissue to rescue the host in the setting of liver injury. \u201cOur BOOST strategy lays the foundation for a future when solid organ cell therapies can be controlled non-surgically according to the needs of patients and their physicians,\u201d Bhatia noted. \u201cBeyond treating liver disease, the premise of BOOST could be applied to other engineered tissue therapeutics that are similarly constrained by challenges associated with tissue scale-up, such as engineered heart or pancreatic tissue to address serious diseases.\u201d
In their paper the authors concluded, \u201c\u2026 this work serves as an exciting proof-of-concept demonstration that scale-up of tissues via growth could be possible \u2026 Together, this work helps lay the foundations for a future of ‘smart’ tissue therapeutics that can be scaled to a patient\u2019s needs and thereby offer treatment for numerous, previously incurable, diseases.\u201d<\/p>\n

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Damage to the liver in patients developing end-stage liver disease has become too severe for the organ\u2019s normally extraordinary regenerative capacity to repair or compensate for that damage. Once this point of no return has been reached the only option is an organ transplant. However, donor livers are in high demand and very limited supply.Ambitious […]<\/p>\n","protected":false},"author":1,"featured_media":10616,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[9],"tags":[],"class_list":{"0":"post-10615","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-science"},"_links":{"self":[{"href":"https:\/\/globalnewstoday.uk\/index.php\/wp-json\/wp\/v2\/posts\/10615","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/globalnewstoday.uk\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/globalnewstoday.uk\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/globalnewstoday.uk\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/globalnewstoday.uk\/index.php\/wp-json\/wp\/v2\/comments?post=10615"}],"version-history":[{"count":0,"href":"https:\/\/globalnewstoday.uk\/index.php\/wp-json\/wp\/v2\/posts\/10615\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/globalnewstoday.uk\/index.php\/wp-json\/wp\/v2\/media\/10616"}],"wp:attachment":[{"href":"https:\/\/globalnewstoday.uk\/index.php\/wp-json\/wp\/v2\/media?parent=10615"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/globalnewstoday.uk\/index.php\/wp-json\/wp\/v2\/categories?post=10615"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/globalnewstoday.uk\/index.php\/wp-json\/wp\/v2\/tags?post=10615"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}