The Tissue: Issue #1
Commentary on cultured meat and its "revolutionary" potential, a reflection on recent news and my Q&A with Dr. James Henstock
7-minute read
Hello enthusiasts for living materials of all sorts!
As this little blog of ours gets up and running again (sprinting even), I’ve been thinking more about how I can add value to your life. More specifically, I’ve been thinking a lot about Twitter, its fall from grace, and what we can do to replace some of the value that has been lost.
Personally, scrolling Twitter was a substantial way I kept up with other scientists in our field (along with a fair share of memes). It’s often how I heard about our field’s newest publications, latest talks, and brightest students, all with an easy mechanism to bookmark tweets that caught my eye for later review when I had more time, energy, and willpower to actually digest them.
Twitter was once the dominant channel through which I connected with our scientific community and yet, today, I hardly use it. Over the last year many of us stepped away from Twitter—either completely or partially—and I know many of you are feeling the loss.
I find myself probing that loss, that wound, asking: Without the old Twitter, how do I keep up with the raging river of publications that continues to flow without end? Where do I go to find the latest, most exciting tissue engineering research? How do I parse through the 20,000 tissue engineering papers published every year without having to work hard searching the internet for something specific? How do I recapitulate the lovely vintage of yesteryear's algorithm—those beautiful moments of chance discovery, of stumbling upon an intriguing thread that makes me ask new, exciting questions—or just go: “Huh. I didn’t know that!”
I’ve been thinking deeply about these questions over the last few months, and it seems like we must take matters into our own hands to fill the void left in Twitter’s stead.
That’s why, once a month, I will be briefly highlighting a few recently published tissue engineering papers that I find to be significant or significantly interesting. And while these “Tissues” (get it? “Tissue” and “Issue” slammed together. You can thank my boyfriend for that one. Still working on the byline though. Suggestions welcome.) will be curated by myself rather than your social media algorithm, I hope that my human touch only enhances their usefulness.
So, without further ado, let’s dive right in to our inaugural transmission—The Tissue: Issue #1!
Growing a Fleshier Future
“Chasing the Paradigm: Clinical Translation of 25 Years of Tissue Engineering”
This 2019 paper out of Robert Langer’s group highlights many of the clinical success stories—including the Dermagraft, INFUSE, and MACI—that leverage biomaterial innovations with or without the use of cells. It’s a lovely, short-ish read also showcasing many of the technologies currently undergoing clinical and large animal trials from vascular replacement to spinal cord regeneration. Importantly, it lays out the challenges that remain and asks: Where we go from here?
Human engineered tissue graft, PeriCord, for the treatment of myocardial infarctions shows promise after Phase I clinical trial
PeriCord, a tissue graft made from the combination of decellularized pericardium tissue sourced from cadavers and human mesenchymal stromal cells isolated from the connective tissue surrounding the umbilical cord (with a wild-sounding manufacturing strategy that involves delivery of the implants to the surgical suite in a three-chamber briefcase), completed its phase I clinical trial to evaluate its ease of surgical use and clinical safety. The implant, used to treat myocardial infarction—which I learned is a scientific word for heart attack—and previously tested in a pig preclinical model, was successfully implanted into 7 patients who received follow up observation out to one year. While there were no significant differences observed between patients who received PeriCord implants and those who received control coronary artery bypass grafts, the data suggests that the PeriCord may promote healing inflammation within the first two weeks following surgery.
“Off-the-Shelf Synthetic Biodegradable Grafts Transform In Situ into a Living Arteriovenous Fistula in a Large Animal Model”
When people experience kidney failure, they often undergo a procedure to connect an artery to a vein, creating an arteriovenous fistula. This arteriovenous fistula serves as a durable access point for repeated hemodialysis. A team of researchers from the Netherlands have created a “synthetic, cell-free, biodegradable, electrospun, anti-kinking scaffold” made through the combination of electrospinning and 3D printing elastic polymers. After testing in goats, they believe this scaffolds has the potential to reduce complications associated with traditional surgical arteriovenous fistula procedures and ePTFE implants. Although these tissue-engineered implants experienced hyperplasia, growing thick vessel walls after three months of implantation, they successfully recruited infiltrating cells to produce collagen and smooth muscle actin. Critically, unlike non degradable ePTFE implants, these biodegradable scaffolds successfully recapitulated the mechanical properties of native vasculature.
The Use of mesenchymal stromal cells for bone regeneration is safe but requires more evidence and standardization to be proven effective in humans
Are you a nerd for mesenchymal stromal cells (MSCs for the fans)? Do you geek out about bone regeneration? Are your dreams (or possibly nightmares) haunted by MSCs crawling through the pores of bony scaffolds? Then this paper is essential reading. The authors review, in lush detail, the impact of mesenchymal stromal cell + scaffold interventions on bone regeneration in humans, specifically focusing on clinical trials over the last 15 years. Before you design your next MSC + scaffold study, give this paper a look.
Commentary on cultured meat and its “revolutionary” potential
Last month the New York Times published an opinion piece on cultured meat, examining if the three billion dollar investment in the field was actually worth it. The article asks: Is cultured meat, as it stands, a legitimate way to battle the climate crisis? The author argues that it isn’t.
Penned by writer and former Deputy Editor of The Counter Joe Fassler, the piece, entitled “The Revolution that Died on Its way to Dinner,” argues in nuanced detail that the cultured meat industry in its entirety is an elaborate and expensive pipe dream. That after a decade of investment, two of the major players in the field have yet to emerge with legitimate products to sell to declining consumer interest and increasingly hostile politicians. In his exposé of Upside Foods published in Wired last fall, Fassler comes to the conclusion that many of us in the wider tissue engineering field hold: Our strategies just aren’t advanced enough to manufacture large vascularized tissues, like muscle, outside of the body.
Ultimately, I find Fassler’s New York Times piece very compelling, specifically his thoughts on why many decided to invest in the first place:
Cultivated meat was an embodiment of the wish that we can change everything without changing anything. We wouldn’t need to rethink our relationship to Big Macs and bacon. We could go on believing that the world would always be the way we’ve known it. Cultivated meat was also a tantalizing spin on a deeply American fantasy: that we can buy our way to a better world.
While I encourage you to read Fassler’s article, I really want to use this space to highlight the response from Isha Datar, Executive Director of New Harvest, “a nonprofit research institute that supports open, public cultured meat research.”
Her response is a well-reasoned, impassioned defense of cellular agriculture as a whole, pointing out the fact that three billion dollars of private funding spread across 150 companies pales in comparison to that of the pharmaceutical industry, which on average “takes 10 years and $1 billion for 1 small molecule drug to come to market.” And surprisingly, her sentiments intertwine with many of the critiques offered by Fassler.
Both Datar and Fassler believe we won’t solve the climate crisis with “business-as-usual” tactics, and that massive investment in a small handful of vertically-integrated startups has not yielded much value to date.
While Fassler suggests we abandon cultured meat entirely, Datar shows us another path, a vision of a tissue engineered future built upon a pipeline of companies, each cultivating specific expertise that can be slotted into a broader supply chain, a robust supply chain that goes well beyond cultured meat, enabling us to better scale living medical technologies as well.
Will cultured meat solve the climate crisis? I don’t think so. But will the field of tissue engineering more broadly benefit from innovations made in cellular agriculture. Absolutely!
Many of the challenges faced by the cellular agriculture industry as they attempt to scale “tissue-engineered” food products are the same challenges we face when scaling tissue-engineered medical technologies. Issues of cell differentiation, vascularization, biomaterial fabrication, bioreactor design, the list goes on and on. Critically, cultured meat necessitates the development of a supply chain that disrupts many of our preconceived notions of how tissue ought to be grown, such as the high price of growth factors or the need for fetal bovine serum in mammalian cell culture media.
Datar’s response reminded me a lot of our Q&A from a few weeks ago with Dr. James Henstock, current Associate Professor in Bioengineering & Cellular Agriculture at Northumbria University and previous senior scientist at Australian cellular agriculture startup Vow.
He ardently believes cultured meat will be a critical enabler for tissue engineering technology of any kind to come to market:
Cultivated meat is driving a new revolution in tissue engineering and bioprocessing, in terms of how you manufacture cells and how you generate a culture environment that you can mature those cells into tissue. In the next three to five years, there’s going to be some big changes led by the cultivated meat industry that change everything we’ll be doing in tissue engineering, partly for reasons of driving down the cost of manufacturing and the scale at which you can make these things. It sets out to subvert the established paradigms we’ve been working off in tissue engineering for a while.
I’m hopeful that investments into cultured meat will translate to benefits for tissue engineering more widely, helping to build out a wider pipeline of support for regenerative technologies that help us all reach our production, sustainability, and patient impact goals—whether or not cultured meat ever reaches commercial scale. To me, that’s worth investing in.
Until next time,
Matthew
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