Latest Developments in Neural and Cardiac Regeneration

Forget what you thought you knew about regenerative medicine. The Q1 2025 Sector Snapshot from ARM reads like a turning point. Cell & Gene Just Hit Reboot And It’s Not Just Hype We’re no longer crawling. We’re sprinting. • In vivo gene editing just entered Phase 3 territory. • Xenotransplantation trials are now FDA-cleared. • Dual-route gene therapy is treating both the heart and brain simultaneously. • CRISPR systems are being shrunk down to go where no Cas9 has gone before. • Parkinson’s, DMD, and Type 1 Diabetes are getting more than hope they’re getting viable clinical candidates. And here’s the kicker: 6 gene therapies could be approved through Accelerated Approval by end of 2026. That’s double what we saw in the entire history of the pathway for gene therapies before now. Meanwhile, VCs are placing big bets: Beam Therapeutics raised $500M. Solid Biosciences: $200M. Umoja Biopharma, Tune, Rhygaze, and others? Backed by serious institutional muscle. But here’s the real question… Are we ready for the moment when cell and gene therapies stop being the exception and start being the standard? Because that moment is coming fast. Welcome to biotech’s version of a software update. Except this time, the code edits DNA. #CellAndGeneTherapy #CGT #BiotechRevolution #InVivoEditing #RegenerativeMedicine #BiotechLeadership Alliance for Regenerative Medicine

Stem Cell Therapy 2.0: Harnessing the Power of Mitochondrial Autophagy The article discusses a recent study explaining how mitochondrial transfer therapy restores damaged heart muscle function. Researchers at Boston Children's Hospital found that transferring small amounts of mitochondria from a patient's healthy skeletal muscle cells to their damaged heart muscle cells can significantly improve heart function and help wean children off ECMO (extracorporeal membrane oxygenation) after congenital heart disease or ischemia-reperfusion injury. The study's findings are truly groundbreaking. Contrary to previous assumptions, the transferred mitochondria don't directly power the heart cells. Instead, they initiate a process called autophagy, where the heart cells break down and recycle their underperforming mitochondria. This leads to a more robust pool of mitochondria within the cells, enhancing their energy production and overall fitness. The researchers are now delving into ways to optimize this therapy, such as engineering off-the-shelf mitochondria or directly triggering the autophagy pathways without transplanting mitochondria. The practical implications of this therapy in cardiac transplantation, particularly for donor hearts after circulatory death (DCD), are immense. These hearts often suffer from ischemic damage. The potential of mitochondrial transfer to preserve and enhance the function of these hearts post-transplantation is a beacon of hope in the field of regenerative medicine. This research represents a significant advancement in stem cell therapy and regenerative medicine, as it provides a new understanding of how mitochondrial transfer works and opens up possibilities for optimizing and expanding its use in various heart conditions. The future of stem cell therapy is poised to be shaped by groundbreaking approaches that harness the body's innate regenerative mechanisms. Mitochondrial transfer therapy stands as a shining testament to the potential of stem cell-based therapies. It demonstrates how we can harness the power of cellular rejuvenation and repair without necessarily relying on direct cell replacement or integration. This innovative approach could herald a new era of more effective and widely applicable regenerative therapies, transcending the boundaries of heart disorders. We will hear and see much more about this. JP https://lnkd.in/eK_AgTwd

🟥 CRISPR-driven Epigenetic Reprogramming for Cell Differentiation and Regenerative Medicine In recent years, CRISPR technology has expanded from genome editing to precisely reprogram cell fate by modifying epigenetic states. By using catalytically inactive Cas9 (dCas9) fused to epigenetic effectors, researchers can regulate gene expression without changing the DNA sequence, providing a powerful and reversible tool for cell differentiation and regenerative medicine. This approach not only has great potential in directing stem cell fate, tissue regeneration, and disease modeling, but also does not have the risks associated with permanent gene modification. CRISPR-driven epigenetic editing enables direct cell reprogramming by activating or repressing lineage-specific genes. For example, dCas9-p300, a histone acetyltransferase, enhances chromatin accessibility and promotes differentiation into neurons, cardiomyocytes, or pancreatic β cells. In contrast, dCas9-KRAB, a transcriptional repressor, silences pluripotency genes and stabilizes differentiation. In addition, TET1-dCas9, a DNA demethylase, removes methylation marks at key promoter regions, reactivating silent genes that are essential for regeneration. This strategy allows researchers to convert fibroblasts into neurons or muscle cells without induced pluripotent stem cells (iPSCs). In addition to reprogramming, CRISPR-epigenetics also enhances stem cell-based therapies by improving iPSC generation and tissue repair. For example, CRISPR-mediated activation of key reprogramming factors such as OCT4, SOX2, and KLF4 increases iPSC efficiency, thereby minimizing the genetic risks associated with viral reprogramming. In addition, epigenetic regulation can enhance immune system regeneration, wound healing, and organ repair by fine-tuning the gene expression profile of transplanted cells. These advances pave the way for the next generation of regenerative medicine. Together, CRISPR-driven epigenetic reprogramming provides a precise, reversible, and non-genetic approach for cell fate engineering. With the improvement of AI-driven gRNA optimization and nanoparticle-based delivery methods, this technology is expected to revolutionize not only tissue engineering, but also regenerative therapies and personalized medicine. Also, these advances offer new hope for treating degenerative diseases, injuries and age-related tissue decline. References [1] Amitava Basu and Vijay Tiwari, BMC Clinical Epigenetics 2021 (https://lnkd.in/eZ6aGsxS) [2] Julian Pulecio et al., Cell Stem Cell 2017 (DOI: 10.1016/j.stem.2017.09.006) #CRISPR #Epigenetics #RegenerativeMedicine #GeneRegulation #TissueEngineering #PrecisionMedicine #CellReprogramming #StemCells #GeneTherapy #BiomedicalInnovation #CSTEAMBiotech

A team of researchers with University of Chicago has developed a wireless device, powered by light, that can be implanted to regulate cardiovascular or neural activity in the body. The featherlight membranes, thinner than a human hair, can be inserted with minimally invasive surgery and contain no moving parts. February 21, 2024 Excerpt: Published Feb. 21 in Nature, the results could help reduce complications in heart surgery and offer new horizons for future devices. “Early experiments have been very successful, and we’re really hopeful about the future for this translational technology,” said Pengju Li, a graduate student at University of Chicago Pritzker School of Molecular Engineering and first author. The laboratory of Prof. Bozhi Tian has been developing devices for years that can use technology similar to solar cells to stimulate the body. Photovoltaics are attractive because they do not have moving parts or wires that can break down or become intrusive—especially useful in delicate tissues like the heart. And instead of a battery, researchers simply implant a tiny optic fiber alongside to provide power. For the best results, scientists had to tweak the system to work for biological purposes, rather than how solar cells are usually designed. “In a solar cell, you want to collect as much sunlight as possible and move the energy along the cell no matter what part of the panel is struck,” explained Li. “For this application, you want to be able to shine a light at a very localized area and activate only that one area.” Note: A common heart therapy is known as cardiac resynchronization therapy, where different parts of the heart are brought back into sync with precisely timed charges. In current therapies, that’s achieved with wires, which can have their own complications. Li and the team set out to create a photovoltaic material that would only activate exactly where the light struck. The eventual design has two layers of a silicon material known as P-type, which respond to light by creating electrical charge. The top layer has many tiny holes—a condition known as nanoporosity—which boost electrical performance and concentrate electricity without allowing it to spread. The result is a miniscule, flexible membrane, which can be inserted into the body via a tiny tube along with an optic fiber—a minimally invasive surgery. The optic fiber lights up in a precise pattern, which the membrane picks up and turns into electrical impulses. The membrane is just a single micrometer thin—about 100 times smaller than the finest human hair—and a few centimeters square. It weighs less than one fiftieth of a gram; significantly less than current state-of-the-art pacemakers, which weigh at least five grams. “The more lightweight a device is, the more comfortable it typically is for patients,” said Li. Publication: Nature Feb. 21, 2024. “Monolithic silicon for high spatiotemporal translational photostimulation.” Li et al,

Can a single gene injection resurrect a failing heart – sounds like science fiction, isn’t it? Except, it’s not. It is a breakthrough in medical science unfolding right now. Researchers at the University of Utah's Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI) have made groundbreaking advancements in treating heart failure through innovative gene therapy. This novel approach, focusing on the cardiac bridging integrator 1 (cBIN1) gene, has demonstrated unprecedented efficacy in reversing heart failure in a large animal model. The study, published in NPJ Regenerative Medicine, utilized a porcine model of non-ischemic heart failure with reduced ejection fraction (HFrEF). The therapy involves administering a harmless virus vector carrying the cBIN1 gene, which is delivered to cardiac cells via bloodstream injection. Key findings of the study: 1. Functional Improvement: The gene therapy resulted in a remarkable 30% improvement in heart function, significantly surpassing previous therapeutic attempts that typically achieved only 5-10% improvement. 2. Survival Rate: All treated subjects survived the entire six-month study duration, a notable outcome given the typically poor prognosis of untreated heart failure in this model. 3. Reverse Remodeling: The treatment induced reverse remodeling of the heart, with treated hearts exhibiting less dilation and thinning, more closely resembling non-failing cardiac morphology. 4. Molecular Mechanism: cBIN1 functions as a centralized signaling hub, regulating multiple downstream proteins and organizing critical heart cell functions. This scaffolding role of cBIN1 is hypothesized to be key to its therapeutic efficacy. 5. Microscopic Improvements: The therapy led to better-organized heart cells and proteins at the microscopic level, suggesting a comprehensive restoration of cardiac ultrastructure. The researchers, led by Dr. Robin Shaw and Dr. TingTing Hong, posit that cBIN1's role as a master regulator of heart cell architecture could introduce a new paradigm in heart failure treatment, directly targeting heart muscle function. While these results are encouraging, human clinical trials are still needed to determine the therapy's effectiveness and safety in people. In collaboration with TikkunLev Therapeutics, the team is adapting the therapy for human application, with plans to seek FDA approval for clinical trials in fall 2025. This research represents a potential paradigm shift in cardiac medicine, as the ability to halt the progression and potentially reverse cardiac damage could revolutionize treatment strategies and significantly improve patient outcomes. #MedicalInnovation #CardiacResearch #GeneTherapy https://lnkd.in/ewkQeSM7

Heart repair via neuroimmune crosstalk The researchers used zebrafish larvae whose heart muscle cells produce a fluorescent substance, making it easy to detect them under a microscope. They then induced an injury similar to a myocardial infarction in the larval hearts and blocked several receptors on the surface of the macrophages. The result was that adrenergic signals from the autonomic nervous system determined whether the macrophages multiplied and migrated into the damaged site. These signals also played an important role in regenerating heart muscle tissue. In the next step, the researchers engineered genetically modified zebrafish in which the adrenergic signal reached the macrophages but could not be transmitted from the receptor into the cell’s interior. “This showed that signal transmission is crucial for heart regeneration,” says the author. If signaling is interrupted, the scarring process is triggered instead. #ScienceMission #sciencenewshighlights https://lnkd.in/dxmpYB7G

I woke up to this news that: Scientists Just Solved Organoids' Biggest Problem! I’m happy to share highlights from a new Science paper by Dr. Oscar Abilez, Dr. Huaxiao 'Adam' Yang, Dr. Joseph C. Wu, and colleagues, a leap forward for organoid technology and regenerative medicine! What Did They Do? Stanford researchers have created the first heart and liver organoids with integrated, functional blood vessels. This solves a critical bottleneck: until now, organoids could only grow a few millimeters before their centers died from lack of oxygen and nutrients. With built-in vasculature, these mini-organs can grow larger, mature further, and better mimic real human tissues. How Did They Do It? *The team meticulously optimized a “recipe” of growth factors and signaling molecules, guiding pluripotent stem cells to differentiate into not just heart or liver cells, but also endothelial and smooth muscle cells that self-organize into branching blood vessels. *Their protocol mirrors early embryonic development, allowing the organoids to achieve a cellular complexity similar to a 6.5-week-old human embryonic heart, including beating function! Why Is This Important? *Better Disease Models: Vascularized organoids allow researchers to study early human development and test how drugs impact organ growth and blood vessel formation. *Personalized Medicine: These models can be tailored from patient-derived stem cells, paving the way for individualized drug testing and disease modeling. *Regenerative Therapies: In the future, vascularized cardiac organoids could be implanted to repair damaged heart tissue, offering a more complete cellular environment than current cell therapies Clinical Context As Dr Joseph C. Wu notes, ongoing clinical studies are already injecting lab-grown cardiomyocytes into patients with heart dysfunction. But real heart tissue is much more complex, containing blood vessels, pericytes, fibroblasts, and more. Vascularized organoids could one day provide all these cell types in a single, implantable tissue patch, dramatically improving integration and function. What’s Next? The team aims to: *Grow organoids longer to assess their maturation and size limits *Further refine the recipes to include immune and blood cells *Adapt this vascularization approach to other organs, moving closer to true “mini-organs” for research and therapy A huge CONGRATULATIONS to the entire Stanford team! References: https://lnkd.in/gmYc-cX9 https://lnkd.in/gbntyWgN https://lnkd.in/g-YT5wdU

𝐀𝐝𝐯𝐚𝐧𝐜𝐢𝐧𝐠 𝐂𝐚𝐫𝐝𝐢𝐚𝐜 𝐑𝐞𝐠𝐞𝐧𝐞𝐫𝐚𝐭𝐢𝐨𝐧: 𝐁𝐫𝐞𝐚𝐤𝐭𝐡𝐫𝐨𝐮𝐠𝐡 𝐢𝐧 𝐡𝐢𝐏𝐒𝐂-𝐃𝐞𝐫𝐢𝐯𝐞𝐝 𝐂𝐚𝐫𝐝𝐢𝐨𝐦𝐲𝐨𝐜𝐲𝐭𝐞𝐬 𝐚𝐧𝐝 𝐂𝐚𝐫𝐝𝐢𝐚𝐜 𝐎𝐫𝐠𝐚𝐧𝐨𝐢𝐝𝐬 I'm excited to share a groundbreaking development in stem cell research by Maksymilian Prondzynski, Paul Berkson, Michael A. Trembley, Yashasvi Tharani, Kevin Shani, Raul H. Bortolin, Mason E. Sweat, Joshua Mayourian, Dogacan Yucel, Albert M. Cordoves, Beatrice Gabbin, Cuilan Hou, Nnaemeka J. Anyanwu, Farina Nawar, Justin Cotton, Joseph Milosh, David Walker, Yan Zhang, Fujian Lu, Xujie Liu, Kevin Kit Parker, Vassilios J. Bezzerides, and William T. Pu, recently published in Nature Communications. Their article, "𝐄𝐟𝐟𝐢𝐜𝐢𝐞𝐧𝐭 𝐚𝐧𝐝 𝐑𝐞𝐩𝐫𝐨𝐝𝐮𝐜𝐢𝐛𝐥𝐞 𝐆𝐞𝐧𝐞𝐫𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐇𝐮𝐦𝐚𝐧 𝐢𝐏𝐒𝐂-𝐃𝐞𝐫𝐢𝐯𝐞𝐝 𝐂𝐚𝐫𝐝𝐢𝐨𝐦𝐲𝐨𝐜𝐲𝐭𝐞𝐬 𝐚𝐧𝐝 𝐂𝐚𝐫𝐝𝐢𝐚𝐜 𝐎𝐫𝐠𝐚𝐧𝐨𝐢𝐝𝐬 𝐢𝐧 𝐒𝐭𝐢𝐫𝐫𝐞𝐝 𝐒𝐮𝐬𝐩𝐞𝐧𝐬𝐢𝐨𝐧 𝐒𝐲𝐬𝐭𝐞𝐦𝐬" (DOI: 10.1038/s41467-024-50224-0), addresses pivotal challenges in cardiac disease modeling and regenerative medicine. The team has developed a robust, scalable, and cost-effective protocol for producing high-quality human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cardiac organoids using stirred suspension bioreactor systems. 𝐊𝐞𝐲 𝐇𝐢𝐠𝐡𝐥𝐢𝐠𝐡𝐭𝐬: 𝐇𝐢𝐠𝐡 𝐘𝐢𝐞𝐥𝐝 𝐚𝐧𝐝 𝐏𝐮𝐫𝐢𝐭𝐲: The optimized bioreactor protocol consistently produced 1.2 million hiPSC-CMs per milliliter with ~94% purity. These cells showed high viability (>90%) post-cryopreservation and primarily ventricular identity, demonstrating superior functional properties compared to standard monolayer-differentiated cardiomyocytes. 𝐑𝐞𝐩𝐫𝐨𝐝𝐮𝐜𝐢𝐛𝐢𝐥𝐢𝐭𝐲 𝐚𝐧𝐝 𝐒𝐜𝐚𝐥𝐚𝐛𝐢𝐥𝐢𝐭𝐲: This protocol showed remarkable reproducibility across various hiPSC lines and batches. Using magnetically stirred spinner flasks further enhanced scalability, allowing cost-effective large-scale production of hiPSC-CMs and cardiac organoids. 𝐅𝐮𝐧𝐜𝐭𝐢𝐨𝐧𝐚𝐥 𝐌𝐚𝐭𝐮𝐫𝐢𝐭𝐲: The bioreactor-derived cardiomyocytes (bCMs) exhibited advanced morphological and functional traits, including mature contractile and electrophysiological properties. These cells outperformed their monolayer counterparts in interbatch consistency and functional assays, making them ideal for disease modeling and therapeutic applications. 𝐈𝐧𝐧𝐨𝐯𝐚𝐭𝐢𝐯𝐞 𝐂𝐚𝐫𝐝𝐢𝐚𝐜 𝐎𝐫𝐠𝐚𝐧𝐨𝐢𝐝𝐬: The protocol’s flexibility enabled the generation of cardiac organoids entirely in suspension culture. These organoids, mainly composed of cardiomyocytes, effectively modeled ventricular wall and chamber formation, offering new possibilities for studying cardiac development and disease mechanisms. This study is a significant leap forward in cardiac regeneration, providing a robust and scalable solution for producing high-quality hiPSC-CMs and cardiac organoids. #CardiacResearch #StemCells #iPSCs #RegenerativeMedicine #NatureCommunications

NEW: 3D-printed Cells May Treat Brain Injuries Neural cells 3D-printed to mimic the architecture of the brain, for the 1st time. A breakthrough technique developed by University of Oxford researchers could one day provide tailored repairs for people with #brain injuries. Study: - Fabricated a two-layered brain tissue - by 3D printing human neural stem cells, - using a droplet printing technique. - When implanted into mouse brain slices, the cells showed - structural and functional integration with the host tissue. 👉 Cortical structure was made from human induced pluripotent stem cells (hiPSCs), which have the potential to produce cell types from most #human tissues. 👉 Key #hiPSCs advantage in tissue repair is that they can be easily derived from cells harvested from patients themselves, and would NOT trigger an #immune response. Future applications: - Evaluation of drugs and therapeutics to promote tissue integration. - Personalized implantation Tx with #3D tissues from a patient’s own hiPSCs Nature | Oct 4, 2023 -- Links in Comments --------------------- Yongcheng Jin, Elina Mikhailova, Ming Lei, Sally Ann Cowley, Tianyi Sun, Xingyun Yang, Yujia Zhang, Kaili Liu, Daniel Catarino da Silva, Luana Campos Soares, Sara Bandiera, Francis Szele, Zoltán Molnár, Linna Zhou, Hagan Bayley. Oxford Martin School, #3Dprinting for Brain #Repair #innovation #technology #future #healthcare #medicine #health #news #management #startups #healthtech #scienceandtechnology #printing #biotechnology #biotech #science #communication #neuralnetworks #research #invivo #neurology #ai #personalizedmedicine #diagnostics  #cell #omics #molecularbiology #drugdiscovery #therapeutics #linkedin #sciencenews #cellandgenetherapy #cellbiology #disease #UK #markers  #neuroscience #electrophysiology #tissueengineering #BDNF #oxford  #engineering #molecularimaging #genetics #neurosciences #bioprinting 3D-printed layered brain tissue (red & blue) using stem cells, which integrated with mouse brain tissue (blue). Yongcheng Jin/U of Oxford