The Impact of Ipscs on Medical Advancements

Overcoming the issue of epigenetic memory in iPS cells is a widely recognized challenge for regenerative medicine. By studying how the epigenome transforms when we reprogram adult skin cells into iPS cells, we discovered a new way to reprogram cells that more completely erases epigenetic memory. We made this discovery by reprogramming cells using a method that imitates how the epigenome of embryo cells is naturally reset. During the early development of an embryo, before it is implanted into the uterus, the epigenetic marks inherited from the sperm and egg cells are essentially erased. This reset allows the early embryo cells to start fresh and become any cell type as the embryo grows and develops. By introducing a step during the reprogramming process that briefly mimics this reset process, we made iPS cells that are more like embryonic stem cells than conventional iPS cells. More effective epigenetic memory erasure in iPS cells will enhance their medical potential. It will allow the iPS cells to behave as "blank slates" like embryonic stem cells, making them more likely to transform into any desired cell type. If iPS cells can forget their past identities, they can more reliably become any type of cell and help create specific cells needed for therapies, like new insulin-producing cells for someone with diabetes, or neuronal cells for someone with Parkinson's. It could also reduce the risk of unexpected behaviors or complications when iPS cells are used in medical treatments. https://lnkd.in/gb235HJP

🟥 "Growing 'Mini Organs' with Blood Vessels in 5 Days: A New Breakthrough in Vascular Organoids" Imagine if we could quickly "grow" miniature organs with blood vessels in the lab. What impact would this have on treating heart disease, diabetes, and even repairing damaged tissue? Recently, scientists have developed a method that makes this possible in just five days—and without the tedious matrix-embedding step. These "vascular organoids" (VOs) are created using induced pluripotent stem cells (iPSCs). The secret lies in the simultaneous activation of two key "switch genes"—ETV2 and NKX3.1. The former pushes cells toward endothelial cell development (forming the inner lining of blood vessels), while the latter transforms them into pericytes (supporting and stabilizing blood vessels). This "two-pronged" strategy, like building both the inner and outer linings of a water pipe, directly assembles a fully functional vascular network. Even more remarkable, when these organoids are placed in a suitable extracellular environment, the blood vessels continue to grow and thicken, forming more complex structures. Single-cell RNA sequencing also shows that scientists can manipulate the timing of gene activation to adjust the type of blood vessels, making them more arterial or more adept at angiogenesis. When scientists transplanted these VOs into immunodeficient mice, they successfully connected with the host's blood system, achieving blood perfusion and promoting revascularization in models of ischemic leg and pancreatic islet transplantation. This suggests that this technology has applications beyond disease research and could become a key component in regenerative medicine and organ transplantation. From a five-day benchtop experiment to a potential life-saving tool in the clinic, this breakthrough brings us one step closer to "on-demand vascularization." In the future, restoring blood flow after a heart attack or reestablishing microcirculation in diabetic patients may require only a single culture dish. Keywords vascular organoids, iPSCs, regenerative medicine, gene regulation, tissue repair Reference [1] Liyan Gong et al., Cell Stem Cell 2025 (DOI: 10.1016/j.stem.2025.05.014)

iPSC-Derived NK Cells and the Future of Immunotherapy - https://lnkd.in/guNdQS47 iPSC-derived NK cell therapies are revolutionizing immunotherapy by providing a scalable, efficient, and targeted approach to treating cancer, inflammatory diseases, and neurological disorders. Unlike traditional donor-derived NK cells, iPSC-derived NK cells offer a limitless and consistent supply, enabling genetic modifications to enhance their therapeutic potential. With the integration of CAR technology and other innovations, these cells represent a promising frontier in personalized medicine. The Australian biotech Cartherics Pty Ltd is at the forefront of advancing iPSC-derived NK cell therapies, developing cutting-edge technologies to enhance their scalability, functionality, and therapeutic potential. By leveraging iPSCs, Cartherics has created a renewable and uniform source of NK cells that can be expanded indefinitely and genetically engineered for precise disease targeting. The company’s proprietary 3D culture systems and bioreactor technologies optimize cell growth and function, ensuring the production of billions of high-quality NK cells without the need for feeder cells. This not only enhances the safety and purity of the final therapeutic product but significantly reduces manufacturing costs and complexity, making NK cell therapy more accessible to patients. Cartherics has taken NK cell engineering a step further by integrating CAR technology into its iPSC-derived NK cells, enhancing their ability to recognize and destroy cancer cells more effectively. Additionally, the company has developed strategies to delete immune suppression genes, which naturally act as regulatory "hand-brakes" in healthy individuals but hinder immune responses in cancer settings. By removing these limitations, Cartherics’ NK cells exhibit heightened cytotoxicity and an improved ability to penetrate solid tumor microenvironments—one of the greatest challenges in immunotherapy. Their lead CAR-NK cell therapy, CTH-401, is set to enter clinical trials for ovarian cancer, marking a significant milestone in the application of iPSC-based NK cell treatments. Beyond cancer, Cartherics is exploring the potential of NK cell therapy for a range of diseases, including endometriosis, Alzheimer’s, Parkinson’s, and traumatic brain injury. Through collaborations with national and international research institutions, the company is investigating how its engineered NK cells can target abnormal cells in various disease settings, offering new hope for patients with conditions that currently lack effective treatments. With its innovative approaches to cell differentiation, genetic engineering, and large-scale manufacturing, Cartherics is a pioneer in the development of next-generation immunotherapies, bringing safer, more effective, and readily available NK cell treatments to the forefront of medicine. #ipscells #nkcells #immunotherapy Richard Boyd Alan Trounson

Scientists Discover “Dynamite” Way To Wipe a Cell’s Memory To Better Reprogram It as a Stem Cell The authors of this article present an important advance in induced pluripotent stem cell (iPSC) technology by developing a transient reprogramming method that generates high-quality iPSCs free of aberrant epigenetic memory. This addresses a significant limitation of conventional iPSC reprogramming using viral vectors, which tends to retain somatic cell memory and dysfunction. The authors utilize a doxycycline-inducible piggyBac transposon system to express reprogramming factors for 36 hours. This transient expression was sufficient to reset the somatic cell epigenome and establish a pluripotent state. The resulting tiPSCs (transient iPSCs) were functionally equivalent to embryo derived ESCs based on transcriptome analysis, differentiation capacity, and ability to generate “all-iPSC” mice via tetraploid complementation. Notably, DNA methylation analysis revealed the tiPSCs had erased somatic memory and acquired an epigenome closely resembling that of ESCs, unlike conventional virally derived iPSCs. This indicates that the short reprogramming window allowed the complete resetting of epigenetic aberrations acquired during somatic cell differentiation. The transient technique also generated IPSCs free of exogenous reprogramming genes, avoiding permanent genetic modification. This study presents a significant technical innovation that improves iPSC quality and removes epigenetic artifacts associated with previous techniques. The ability to generate high-quality iPSCs free of aberrant epigenetic memory and somatic cell dysfunction will enhance the functionality of iPSC-derived cells for regenerative therapies. Conventional iPSCs retain some epigenetic memory that can impair differentiation or cause abnormal function. The ability to rapidly generate high-quality, integration-free iPSCs will benefit stem cell research and potential therapeutic applications. This transient approach could become the new gold standard protocol for iPSC generation. I read the complete article.    Overall, by improving iPSC quality and removing safety concerns over genetic modification, this new transient reprogramming paradigm represents a major step forward for the clinical translation and adoption of iPSC-based regenerative medicine. Resolving prior technical issues brings the field closer to realizing the potential of iPSCs for diverse therapeutic applications. I've included the shorter review below. JP https://lnkd.in/etewNs94

Kidney models-on-a-chip. Developing advanced drug screening tools is crucial for the advancement of personalized medicine and the creation of more effective treatments through disease modeling. Kyoto University, Japan. 20 September 2024. Key: Assessment of Drug Transport and Nephrotoxicity; Patient derived stem cells. Excerpt: The kidney's proximal tubules are essential for reabsorbing critical substances from the bloodstream before urine formation. Traditional in vitro models have struggled to accurately replicate this, often failing to express key transport proteins like organic anion transporters -- OAT1/3 -- and organic cation transporter 2 -- OCT2. A team at Kyoto University has developed a human iPS cell-derived kidney organoid-based proximal tubule-on-chip -- OPTECs-on-Chip -- that mimics in vivo renal physiology more closely than ever before. This model exhibits enhanced expression and polarity of essential renal transporters, making it a powerful tool for assessing drug transport and nephrotoxicity. "Our OPTECs-on-Chip demonstrates significant improvements in the expression and functionality of OAT1/3 and OCT2 transporters compared to previous models using immortalized cells," explains lead author Cheng Ma from KyotoU's Graduate School of Engineering. Note: "Listening to the needs of pharmaceutical companies to develop the high-function kidney chip is the best way for us to integrate MPS technology into drug development," explains team leader Ryuji Yokokawa at KyotoU's Department of Micro Engineering. "We demonstrated that our OPTECs-on-Chip not only assesses nephrotoxicity but also quantifies transcellular substrates transported specifically by OAT1, OAT3, and OCT2. This highlights the benefits of using iPS cell-derived cells and a microfluidic system to replicate in vivo cellular transport mechanisms," add co-author Minoru Takasato at the RIKEN Center for Biosystems Dynamics Research, together with Toshikazu Araoka of KyotoU's Center for iPS Cell Research and Application. Yokokawa's team anticipates applying their MPS model as a screening tool for developing new drugs by evaluating the transport and nephrotoxicity of various membrane proteins. "Our model has significant potential for drug screening and personalized medicine," notes Yokokawa. "By incorporating patient-derived stem cells, we can develop personalized assessments for renal transport and disease modeling." Refer to enclosed announcement to access direct link to published research. https://lnkd.in/eMpWBVnW

Lab grown stem cells could be a breakthrough for cancer treatment Scientists in Australia have made a groundbreaking discovery that could revolutionize bone marrow transplants. By utilizing patient-derived induced pluripotent stem cells (iPSC), they have successfully developed transplantable blood stem cells that closely resemble those found in human embryos. 𝐓𝐡𝐢𝐬 𝐢𝐧𝐧𝐨𝐯𝐚𝐭𝐢𝐯𝐞 𝐩𝐫𝐨𝐭𝐨𝐜𝐨𝐥 𝐞𝐥𝐢𝐦𝐢𝐧𝐚𝐭𝐞𝐬 𝐭𝐡𝐞 𝐧𝐞𝐞𝐝 𝐟𝐨𝐫 𝐝𝐨𝐧𝐨𝐫 𝐦𝐚𝐭𝐞𝐫𝐢𝐚𝐥, 𝐩𝐚𝐯𝐢𝐧𝐠 𝐭𝐡𝐞 𝐰𝐚𝐲 𝐭𝐨 𝐩𝐫𝐨𝐝𝐮𝐜𝐞 𝐛𝐥𝐨𝐨𝐝 𝐬𝐭𝐞𝐦 𝐜𝐞𝐥𝐥𝐬 𝐜𝐚𝐩𝐚𝐛𝐥𝐞 𝐨𝐟 𝐠𝐞𝐧𝐞𝐫𝐚𝐭𝐢𝐧𝐠 𝐫𝐞𝐝 𝐜𝐞𝐥𝐥𝐬, 𝐰𝐡𝐢𝐭𝐞 𝐛𝐥𝐨𝐨𝐝 𝐜𝐞𝐥𝐥𝐬, 𝐚𝐧𝐝 𝐩𝐥𝐚𝐭𝐞𝐥𝐞𝐭𝐬. “The ability to take any cell from a patient, reprogram it into a stem cell and then turn these into specifically matched blood cells for transplantation will have a massive impact on these vulnerable patients’ lives,” Professor Constanze Bonifer In the study, immune deficient mice were injected with the lab engineered human blood stem cells. They found the blood stem cells became functional bone marrow at similar levels to that seen in umbilical cord blood cell transplants, a proven benchmark of success. What sets stem cell therapy apart is its ability to continuously regenerate within the patient, providing a lasting cure. Very excited to see this work enter the clinic and its applications in the neurodegeneration and longevity fields. To learn more about the research: https://lnkd.in/dgjQyu7J https://lnkd.in/dV5tsMbY 🩸 #StemCellResearch #MedicalBreakthrough #ScienceInnovation

Today, we report a new self-organizing organoid system in Nature Biomedical Engineering that includes functional organ-specific vasculatures woven in human iPS cell-derived liver bud organoids. By devising a developmental biology-inspired protocol for liver sinusoidal endothelial progenitors, and integrating them into a multilayer air-liquid interface culture (IMALI), we achieved organoids that: • Coax hepatoblast, mesenchyme, arterial and sinusoidal progenitors entirely from iPS cells • Enable enhanced maturation via WNT2-mediated sinusoid-hepatocyte crosstalk • Form branched, perfused sinusoid-like vessels in vivo after transplantation • Secrete key coagulation factors, including FVIII, correcting bleeding in haemophilia A mice These findings offer a powerful platform to study liver vasculature development and open up new therapeutic possibilities for coagulation disorders. See full article from here: https://rdcu.be/etlBl Congrats to Norikazu Saiki, Yasunori Nio, all collaborators including Ya-Wen Chen and co-authors Institute of Science Tokyo (Science Tokyo) Cincinnati Children's The University of Osaka Mount Sinai Health System ! #Organoids #LiverResearch #StemCells #VascularBiology #Haemophilia #iPSC #RegenerativeMedicine #NatureBiomedicalEngineering

#NIH to Prioritize Human-Based Research Technologies Big news in biomedical research! The NIH is prioritizing human-based technologies to reduce animal testing, following the #FDA announcement earlier this month. #iPSCs (induced pluripotent stem cells) will be at the heart of this transformation. Why are iPSCs so crucial? They allow scientists to create realistic human #organoids and #OrgansOnAChip – miniature 3D tissues and multi-organ systems in the lab. Derived from human cells, these models offer unprecedented insights into disease mechanisms and drug responses that are far more relevant to people than traditional animal models. Beyond lab models, data from iPSC-based systems is fueling advanced #ComputationalModels and #AI, helping predict drug efficacy and toxicity with greater accuracy. This shift, supported by the new NIH Office of Research Innovation, Validation, and Application (ORIVA), promises to accelerate discoveries, improve human health outcomes, and usher in a new era of more ethical and predictive research. https://lnkd.in/gms6jsey #HumanBasedResearch #Biotechnology #DrugDiscovery #Science #Innovation #StemCells #CellTherapy #GeneTherapy

From Paralyzed to Standing, Recent Stem Cell Breakthroughs in the U.S. and Japan Offer New Hope for Spinal Injury Recovery: 🇺🇸 U.S. (Mayo Clinic) Chris Barr, an American man paralyzed from the neck down after a surfing accident, became the first patient in a Mayo Clinic clinical trial. Doctors harvested stem cells from his abdominal fat, expanded them to 100 million cells, and injected them into his spinal cord. Over five years, Barr regained the ability to walk, feed himself, and perform daily activities. In the trial of 10 patients, seven showed improved motor function and sensation, while three saw no change. The therapy is still experimental but shows potential for treating spinal cord injuries 🇯🇵 Japan (Keio University) In Tokyo, researchers at Keio University (慶應義塾大学) treated four men with recent complete spinal cord injuries using neural stem cells derived from induced pluripotent stem cells (iPSCs). Each patient received approximately two million cells injected into their spinal cord. One patient improved from complete paralysis (AIS grade A) to being able to stand and is now learning to walk. Another regained partial limb movement. Even the two who remained at grade A experienced subtle motor improvements. While the sample size is small, the results are extremely promising 👇Source articles in comments #HealthTech