The Tissue: Issue #3
ARPA-H awards $190 million to develop transformative osteoarthritis therapies and my lab's latest paper!
7-minute read
Hello enthusiasts for living materials of all sorts,
I blinked, and suddenly May is gone! To keep it brief, May was a pretty calm month in the lab. Lots of prep for experiments happening this summer, saying a difficult goodbye to my awesome undergrad as she graduated (she’s on the job market btw), and simultaneously mourning/celebrating not having any students to mentor this summer (I love them, but it’s a ton of work and now I can take off whenever I want).
ARPA-H awards $190 million to develop transformative osteoarthritis therapies
ARPA-H, the Advanced Research Projects Agency for Health launched in 2022, announced its NITRO funding recipients on March 26th. NITRO (aka “Novel Innovations for Tissue Regeneration in Osteoarthritis”) is the largest single public investment in osteoarthritis research and will fund five teams to develop “injectable and implantable regenerative therapies” over the next five years. The program has an ambitious aim (to eradicate osteoarthritis), an ambitious price tag (up to $190 million), and an ambitious timeline—the five teams are tasked with bringing transformative therapies to phase 1 clinical trials by 2028.
According to ARPA-H and its institutional leads, the teams will be developing a wide variety of technologies spanning three focus areas:
Injectable and/or nan-invasive bone regeneration
Injectable and/or non-invasive cartilage regeneration
Replacement joints built from human cells
The first three teams are focused on NITRO’s first two technical areas, developing therapies that modulate the regeneration of osteoarthritic cartilage and its neighboring bone.
Awarded up to $33 million, the team led by Duke University in conjunction with Boston Children’s Hospital and UCLA, will develop controlled-release therapies that reactivate the healing response of cells residing in degenerated cartilage and bone. The University of Colorado Boulder is leading a $39 million research team developing injectable nanoparticles and other biomaterial therapies that support whole joint regeneration strategies. Finally, the team led by Washington University in St. Louis, awarded up to $31 million, will focus on developing a cell therapy it refers to as “Stem cells Modified for Autonomous Regenerative Therapy”—aka “SMART” Their SMART gene-edited cells have the potential to successfully modulate healing by localizing to sites of inflammation and producing anti-inflammatory drugs when implanted in the osteoarthritic joint.
The remaining two research teams, one led by Columbia University and the other led by Case Western Reserve University, are both tasked with creating living joint replacements.
Unlike traditional metal and plastic arthroplasties, these entirely tissue-engineered implants will be alive, crawling with cells to initiate healthy joint remodeling and restore dynamic joint function. The Columbia team, receiving up to $39 million, will develop a total knee replacement they’re calling “NOVAJoint,” for which they’ll test both patient-specific cells and donor cells to create. The Case Western Reserve team, receiving up to $47.7 million, will develop a modular tissue-engineered modular joint grown from both human bone and cartilage cells.
As someone who works full time on intervertebral disc and cartilage tissue regeneration, I’m particularly excited to watch how these initiatives unfold over the next five years. Hopefully this massive influx of support from ARPA-H will remove critical barriers preventing regenerative therapies from moving from the lab bench to the operating room. Until then, I’ll be watching closely for you, waiting to report back.
New and Interesting Publications
Gene-edited SMART macrophages mitigate harmful inflammation in the knee joint through the local delivery and production of IL-1 receptor antagonist
Speaking of WashU’s NITRO award, a new preprint characterizing the application of their SMART cell therapy in vivo was released last week. Dr. Guilak’s research team delivered their genetically-engineered macrophages to two different mouse models: (1) mice with acute cartilage injuries and (2) mice with an inflammatory joint condition that mimicked rheumatoid osteoarthritis. The SMART cells remained active for up to seven days after injection in both groups of mice and were able to significantly reduce inflammation. Because the injected cells produced IL-1 receptor antagonist in situ, they prolonged the residence time of the drug in the joint space, leading to the maintenance of healthy cartilage in a group of strong responder mice. It’s fascinating and creative work, and I’m looking forward to seeing how they use the NITRO award to further develop this technology!
“From Promise to Practice: Recent Growth in 30 Years of Tissue Engineering Commercialization”
In Tissue #1 we featured a 2019 paper out of the Langer Lab chronicling the last 25 years of tissue engineering. I was super excited to see the follow up to that review drop a few days ago. While the 25th anniversary paper examined how far we’ve come as a field, this latest review examines where we’re going amid the shifting commercial trends of the last five years. The authors break down what therapies are currently clinically available as well as what kind of therapies are being investigated through ongoing clinical and preclinical trials. The authors had the following to say about our field’s future: “Most of the companies we identified that were in clinical trials were investigating stem cell therapies (68%), followed by therapies involving both cells and biomaterials (26%), and those utilizing only biomaterials (5%). While biomaterial products still represent a substantial portion of commercial and preclinical products, the functionalization of these materials with bioactive cellular products is now more dominant in the field—a shift only realized in the last five years.” It’s a great, succinct read on the state of our field’s push toward commercialization. 10/10.
Clinical trials investigating stem cell injections for the treatment of low back pain are vastly underreported compared to their orthopaedic counterparts
Spine researchers gather round! Clinical trials investigating the use of intradiscal stem cell injections for the treatment of low back pain are vastly underreported (I’m screaming. And crying). Out of 26 clinical studies, only 11 (42.3%) were completed, and only 7 of those were published (26.7%). The studies scrutinized a variety of cell types both with and without the use of carrier materials. The authors emphasize that a variety of factors may contribute to a study’s early termination or non-publication. Low back pain is often non-specific, and treatment of a degenerative disc alone using these cell therapies may not relieve a patient’s pain, confounding the study results. Notably, only two of the studies reviewed involved the co-treatment of the disc and its adjacent facet joints. Patient’s may drop out of a study to pursue other forms of treatment as their back pain intensifies, reducing its statistical power, or the high cost of scaling autologous MSC therapies may lead to a company pulling the plug on a study entirely. There are other gems in here, but I’ll let you discover them for yourself!
.jpg){kind=link}
Vascularization of extracellular matrix-derived hydrogels in vitro depends on the source of the decellularized tissue
I think this is a super fascinating study that reveals something important about biomaterials created with decellularized extracellular matrix (ECM). The source of that tissue really matters! Researchers from the University Medical Center Groningen compared ECM hydrogels fabricated from the skin or the lungs of pigs, as well as a mix of the two materials. Skin-derived ECM hydrogels supported more vascularization than lung-derived ECM hydrogels did, and this difference seemed to be driven most prominently by material mechanics. I’d love to see a more intense mechanobiological investigation of this work with an expanded tissue library. What do you think?
Intervertebral disc degeneration instigates vertebral endplate remodeling and facet joint pathology in a large animal model
Last on the docket this month, I have the exciting opportunity to share some newly published work out of my lab with you. If you are interested in knowing more about the type of research I have the immaculate privilege of participating in, feel free to check out the latest paper from our spine research group. It’s all about the crosstalk that occurs between spinal tissues as the intervertebral disc degenerates in a goat model.
Although our lab and others have looked at this preclinical model of intervertebral disc degeneration (IVDD) before, we’ve been taking a holistic approach to better understand how it recapitulates the full spectrum of human disease so we can more effectively test new therapies for the treatment of IVDD and its associated pain.
As teased in the discussion, other members of my lab are currently examining additional tissue crosstalk in these goat degenerative discs, including with the adjacent paraspinal muscles and cellular mediators of inflammation, to build an even more complete picture of this whole spine disease. So stay tuned!
Somehow I’ve tricked my boss into letting me draw on the job, and I was able to sneakily design our study schematic—including our friendly little goat—instead of pipetting at my bench. Let’s hope she doesn’t catch on anytime soon!
Until next time,
Matthew
Have news you want to share with the Fleshy Futures community, leave it in the comments below!