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Mimicking vaginal cells and microbiome interactions on chip microfluidic culture
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
Scientists at Harvard University’s Wyss Institute for Biologically Inspired Engineering have developed the world’s first “vagina-on-a-chip,” which uses living cells and bacteria to mimic the microbial environment of the human vagina. It could help to test drugs against bacterial vaginosis, a common microbial imbalance that makes millions of people more susceptible to sexually transmitted diseases and puts them at risk of preterm delivery when pregnant. Vaginal health is difficult to study in a laboratory setting partly because laboratory animals have “totally different microbiomes” than humans. To address this, scientists have created an unique chip, which is an inch-long, rectangular polymer case containing live human vaginal tissue from a donor and a flow of estrogen-carrying material to simulate vaginal mucus.
The organs-on-a-chip mimic real bodily function, making it easier to study diseases and test drugs. Previous examples include models of the lungs and the intestines. In this case, the tissue acts like that of a real vagina in some important ways. It even responds to changes in estrogen by adjusting the expression of certain genes. And it can grow a humanlike microbiome dominated by “good” or “bad” bacteria. The researchers have demonstrated that Lactobacilli growing on the chip’s tissue help to maintain a low pH by producing lactic acid. Conversely, if the researchers introduce Gardnerella, the chip develops a higher pH, cell damage and increased inflammation: classic bacterial vaginosis signs. So, the chip can demonstrate how a healthy / unhealthy microbiome affects the vagina.
The next step is personalization or subject specific culture from individuals. The chip is a real leap forward, it has the prospect of testing how typical antibiotic treatments against bacterial vaginosis affect the different bacterial strains. Critics of organ-on-a-chip technology often raise the point that it models organs in isolation from the rest of the body. There are limitations such as many researchers are interested in vaginal microbiome changes that occur during pregnancy because of the link between bacterial vaginosis and labor complications. Although the chip’s tissue responds to estrogen, but it does not fully mimic pregnancy without feedback loops from other organs. The researchers are already working on connecting the vagina chip to a cervix chip, which could better represent the larger reproductive system.
All these information indicate that the human vagina chip offers a new model to study host-vaginal microbiome interactions in both optimal and non-optimal states, as well as providing a human relevant preclinical model for development and testing of reproductive therapeutics, including live bio-therapeutics products for bacterial vaginosis. This microfluidic human vagina chip that enables flow through an open epithelial lumen also offers a unique advantage for studies on the effect of cervicovaginal mucus on vaginal health as clinical mucus samples or commercially available mucins can be flowed through this channel. The role of resident and circulating immune cells in host-microbiome interactions also can be explored by incorporating these cells into the vagina chip in the future, as this has been successfully done in various other organ chip models.
Affymetrix to Stick With Thermo Fisher’s Takeover Proposal
SAN FRANCISCO — What briefly appeared to be a potential bidding war for Affymetrix, a genetics analysis technology maker, fizzled out on Monday after the company chose to stick with a takeover bid from Thermo Fisher Scientific over a higher bid from a Chinese-backed suitor.
In a statement, Affymetrix reiterated its support for the $14-a-share offer from Thermo Fisher that it accepted in January.
In a statement, Affy said that based on the terms of the new offer, it determined that failure to engage with Origin on its bid could reasonably be expected to be “inconsistent with the board’s duties under Delaware law.”
However, Affy said that its board continues to recommend that its stockholders vote in favor of the adoption of the merger agreement with Thermo Fisher, explaining that it “has not determined that the Origin proposal is in fact a ‘superior proposal’ for purposes of the merger agreement with Thermo Fisher and is not making an adverse recommendation change.
“We fully expect that the Affymetrix board of directors will promptly conclude that our transaction remains the only bona fide alternative for Affymetrix stockholders and, as contemplated by the terms of our merger agreement, will definitively recommend against the Origin Technologies proposal and in favor of the Thermo Fisher transaction prior to the upcoming stockholder meeting,” Thermo Fisher President and CEO Marc Casper said in a statement this morning.
“Origin Technologies has still not addressed the fundamental flaws of its proposal, which has remained from its first announcement highly contingent, uncertain, and insufficient,” he added.
NEW YORK (GenomeWeb) – Origin Technologies Corporation, founded by former Affymetrix executives for the purpose of purchasing the company, proposed today to acquire Affy for $16.10 per share in an all-cash transaction valued at approximately $1.5 billion.
The proposal comes about a week before Affy shareholders are scheduled to vote on a different deal, Thermo Fisher Scientific’s proposed acquisition of Affy for approximately $1.3 billion, which the boards of directors of both firms unanimously approved in January.
According to a letter sent by Origin to Affymetrix today, its proposal represents a 75 percent premium to Affymetrix’s unaffected closing share price of $9.21 on the last trading day prior to the announcement of Thermo Fisher’s proposed acquisition.
Fully financed by SummitView Capital, Origin said its all-cash offer represents a 15 percent premium for Affy stockholders relative to the proposed transaction with Thermo, under which stockholders would receive $14.00 per share in cash.
As part of the offer, Origin also pledged to fund payment of the $55 million termination fee that would be due to Thermo under the terms of Thermo and Affy’s January agreement.
Wei Zhou, president of the newly formed Origin, wrote in the letter to Affy today that Origin strongly believes that its offer is superior to Thermo’s based on several criteria.
First, it offers substantially higher value to Affy’s stockholders, he said. Additionally, Origin believes it is in a better position to help Affy achieve its potential as a standalone, global company focused on genomics and proteomics. The deal would also offer an opportunity to acquire new technologies in the complete human genome sequencing space, Zhou wrote.
If the Origin-Affy merger goes through, Origin would have a separate option of combining with another company founded by Zhou in 2009, Centrillion Technology Holdings Corporation.
Thermo Fisher Scientific to acquire Affymetrix for $1.3 billion
WALTHAM, Mass. – Thermo Fisher Scientific Inc., announced Jan. 8 that it has agreed to acquire Affymetrix Inc. for $14.00 per share in cash, or roughly $1.3 billion. The transaction, approved by the boards of directors of both companies is pending shareholder approval and is expected to close in the second quarter this year.
Santa Clara, Calif.-based Affymetrix was founded in 1992 and is a pioneer in the field of
microarray technology, launching its
GeneChip line in 1994. Today, the company serves both the
life sciences research and
clinical markets
Over the past ten years, the company has broadened its portfolio of tools that enable both
multiplexed and
parallel analysis of
biological systems at the cell, protein and genetic level.
Notable acquisitions for Affymetrix have included genetic tools company ParAllele Bioscience (2005), genetic, protein and cellular analysis provider Panomics (2008), and eBioscience (2012), which included one of the world’s largest selections of
antibodies,
ELISAs, and
proteins
for life science research and diagnostics.
“The acquisition of Affymetrix will strengthen our leadership in biosciences and create new market opportunities for us in genetic analysis,” said Marc N. Casper, president and CEO of Thermo Fisher Scientific. “In biosciences, the company’s antibody portfoliowill significantly expand our offering in the fast-growing flow cytometry market, and customers will have greater access to these products through our global scale and commercial reach. In genetic analysis, Affymetrix’s technologies are highly complementary and present new opportunities for us in targeted
clinical and
applied markets.”
According to Frank Whitney, president and CEO of Affymetrix, the acquisition will allow the company to continue to build upon the close relationships it has created with customers, while deepening its reach into the biopharma market. “We are excited about the opportunity to combine our portfolios and strengthen our position in high-growth markets such as
single-cell biology
reproductive health and
AgBio
According to information provided by Thermo Fisher, benefits of the acquisition include expanding its offerings of its antibody portfolio via the eBioscience line of products, which also includes
multiplex RNA,
protein assay
single-cell assays
genetic analysis capabilities via complementary products used in
cytogenetics
genotyping and
gene expression.
Thermo expects Affymetrix will add $0.10 in adjusted earnings per share in the first full year of ownership, while creating $70 million in operational savings by year three. Affymetrix has annual revenues of approximately $350 million and will be integrated within Thermo Fisher’s Life Sciences Solutions business unit.