I’m back with a post-holiday double edition of RMNU🔬! I cover stem cell patches for failing hearts, a novel skeletal tissue that’s been (re-)discovered, an update on BlueRock’s Parkinson’s therapy, and more. Bookmark, or dive right in!
Pick of the Month(s)
Stem cell patches for failing hearts
Around the globe, around 5000 heart transplants are completed each year. Is that less than you imagined? If so, you’d be justified in expecting more; the supply of hearts simply cannot keep up with the demand created by almost 50,000 additional patients on waiting lists. Given that heart disease is the world’s leading cause of death, this is a major problem.
Last month, Jebran et al. reported a 2021 case study wherein a 46-year-old woman with heart failure received 10 off-the-shelf patches made from stem cells. These were intended as a potentially stabilizing measure, testing whether this treatment could re-muscularize her heart as she waited for a transplant. Fortunately, she received her new organ three months later, allowing the patched one to be examined by the authors.
In the past, cardiac treatments involving stem cells – or stem cell-derived muscle tissues – have resulted in complications including irregular heartbeat, tumour growth, and immune rejection. Such procedures involved either implantation or direct injection of the cell therapies into the organ.
To avoid these serious complications, Jebran et al. designed their patches, also known as epicardial engineered heart muscle allografts, to be stitched onto the outside of the heart. This means they do not fully integrate into the old tissue, though blood vessels were found to infiltrate and feed the therapeutic cells. Instead of integrating, the new cells responded to the heart’s movement, allowing the organ itself to lead the way while enhancing the overall strength of each pump. Metrics obtained from macaque data reported in the same paper included a 15 per cent increase in the heart wall’s thickness relative to controls, plus a 10 per cent uptick in the volume of blood pumped per heartbeat six months post-operatively.
The patches were made by first differentiating induced pluripotent stem cells (iPSCs) into heart muscle and connective tissue. These cells were then incorporated into a collagen gel. Because the grafts were created using materials from an allogeneic source, immunosuppressants were required. However, the authors opted for the type that might’ve already been used for the heart transplant itself (tacrolimus and methylprednisolone).
Another 15 patients have received these patches as part of an ongoing trial. In addition, new patch designs that minimize the need for immunosuppressive drugs are also being tested.
For a longer summary of this story, check out Miryam Naddaf’s piece in Nature News.
Other cardiac-themed research studies getting attention:
- Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs.
- Follistatin from hiPSC-cardiomyocytes promotes myocyte proliferation in pigs with postinfarction LV remodeling.
New textbook editions incoming: (Mostly) novel skeletal tissue discovered
Thanks to work by Ramos et al. at the University of California Irvine, we now have a new type of tissue on record: Lipocartilage. It can be found in the mammalian ear, nose, larynx and sternum. It’s best suited for flexible body parts, such as the earlobes or the tip of your nose, and is thus more pliable than tougher knee cartilage, for example. Why does the title read, “mostly novel”? Well, lipochondrocytes were first observed by Franz von Leydig – yes, the namesake of the Leydig cell – in 1854. His observation was then somehow lost to time, until now.
Functionally, lipocartilage holds promise as a positive new addition to the reconstructive toolkit. This is especially true for facial defects or elective augmentations, injuries and diseases that result in damaged cartilage: think cleft palates, a damaged larynx caused by cancer, or even rhinoplasties. Current methods in surgeries necessitating cartilage are highly invasive and/or aren’t always the best biomechanical match, including harvesting from a patient’s rib before subsequent transplant to the desired region. Silicone also tends to be used. Fortunately, the future does look brighter on this front: The authors detected lipocartilage not only in vivo, but also in human cartilage cultures grown in vitro using embryonic stem cells. This means they’re already accessible to scientists for regenerative medicine applications, and some teams will now be looking to iPSCs as a potential source.
From function to physiology, these cells are quite unique: lipochondrocytes are stable reservoirs of lipids that do not change size in response to calorie intake or diet. Fat breakdown is prevented in the cells’ vacuoles, keeping their structures consistent. Lipocartilage thus remains soft, pliable and supportive, similar to bubble wrap (according to the authors). That these cells derive their biomechanical properties from the organelles inside of them is a stark contrast to traditional cartilage, which is dependent on extracellular matrix for its sturdiness. Interestingly, even their fat comes from a different source than the well-known adipocyte: Lipochondrocytes produce their own using glucose, while adipocytes absorb dietary fat.
The team looked at rodents and human fetal tissue, but also 65 other mammalian species. Their investigation even extended to bats, where lipocartilage was found to be patterned; parallel ridges enhance the animals’ hearing by attuning them to specific sound waves. However, lipochondrocytes were not found in non-mammalian species, raising questions about why this cell type might be unique to class Mammalia.
For more on this story, check out Aguayo and Selleri’s Science Perspectives piece.
BlueRock’s bemdaneprocel heads to Phase III
You might recall my coverage of BlueRock Therapeutics’ stem cell therapy for Parkinson’s disease (PD), bemdaneprocel, posted last year. They had just received the U.S. Food and Drug Administration’s (FDA) RMAT designation following positive results in a Phase I clinical trial with 12 participants. At the time, they were slated to initiate their Phase II trials; this is no longer the case, as they’ve just been authorized to head into Phase III given the positive data thus far. If the trial goes well, regulatory submissions for marketing authorization will follow, as this jump to Phase III is intended to bring the drug to market sooner (should it perform as expected).
A quick refresher: BlueRock’s protocol involves the reprogramming of embryonic stem cells to dopamine precursor cells, which are subsequently implanted into the patient’s brain. Their therapy was found to be well-tolerated with no major safety concerns over the course of a 24-month follow-up period (with immunosuppressant drugs administered for the first year). While this trial was not necessarily designed to assess efficacy, as Phase I is mainly for safety and dosing, patients did appear to improve with regard to exploratory clinical endpoints – particularly those in the group receiving a higher dose.
Moving into the next phase of study now, exPDite-2 (which does not yet appear to be in the registry) is a double-blind trial designed to assess the efficacy, safety and overall impact of bemdaneprocel. Approximately 102 participants with moderate PD are anticipated.
Notably, this trial will be the first Phase III study involving an allogeneic pluripotent stem cell-based therapy for PD. Read Bayer’s full release here.
See also the following headline from their iPSC-based competitors, Aspen Neuroscience:
First FDA-Approved Mesenchymal Stromal Cell Therapy
This past December, the FDA approved Ryoncil (remestemcel-L-rknd), an allogeneic bone marrow-derived mesenchymal stromal cell (MSC) therapy developed to treat steroid-refractory, acute graft-versus-host disease (GVHD) in pediatric patients.
You may or may not be surprised to hear that the U.S. is not the first country to approve this drug; in fact, Canada granted Prochymal – as it was called back then – conditional approval back in 2012, and in doing so was considered the world’s first regulatory authority to approve a stem cell-based therapy (though again, it was conditional pending further data). New Zealand also conditionally approved the drug that year. Despite these green lights, subsequent clinical use seems to have been limited. Osiris ultimately licensed the intellectual property and sold the drug to Mesoblast for US$50 million in 2013. Mesoblast worked to optimize manufacturing, and rebranded the drug as Ryoncil.
On the other hand, in Japan, the product was licensed to JCR Pharmaceuticals Co. Ltd. and branded as TEMCELL. It was here that the drug’s first full, non-conditional approval was handed down in 2015.
The drug’s approved indication is acute GVHD, which is a serious complication that usually occurs in the first 100 days following an allogeneic stem cell transplant. Donor stem cells develop into the recipient’s new immune system, but aberrantly attack healthy cells as though they’re foreign, causing damage to tissues and organs. Some patients never develop GVHD, but it can occur in up to 40 per cent of cases, ranging from mild to severe. The skin, liver and intestines are often affected, but other organs may be targeted as well. To combat the disease, MSCs produce strong anti-inflammatory effects, modulating the pathological immune response.
For more, check out the FDA’s release linked above, or this summary from the American Association for Cancer Research.
Phase I trial of stem cell transplants for spinal cord injury: Results
The data are officially in from a Phase I clinical trial testing the safety and feasibility of neural stem cell transplantation in the treatment of chronic thoracic spinal cord injuries, which often result in partial or full paralysis. Martin et al. published their results in Cell Reports Medicine just before the holidays last year. Four patients with chronic spinal cord injuries received six bilateral injections of fetal-derived neural stem cells capable of forming neurons and their support lineages, including astrocytes and oligodendrocytes. These particular stem cells were chosen for their preclinical track record of promoting repair without leading to unwanted complications, such as tumour formation. Following surgery, participants were followed for five years.
Two patients demonstrated neurological improvements following treatment, including higher motor and sensory scores, and enhanced electromyography activity in muscles that had previously been considered dormant. Some participants’ pain scores also improved. However, overall mobility and independence scores did not see significant enhancements, emphasizing the need for further research and variable optimization. Of course, being a Phase I trial, only safety and tolerability were meant to be assessed either way, but these early neurological results may hint at therapeutic potential. The researchers are now moving towards a Phase II clinical trial to ascertain the transplant’s true efficacy.
It should be noted that one of the patients in this trial passed away; I didn’t see this in the UCSD release, but it bears mentioning. This was the one serious adverse event recorded in their trial. The participant died of sepsis, likely related to a sacral ulcer 30 months post-transplant. The authors don’t attribute this to the stem cells or the transplant surgery; a reasonable conclusion, given that patients with neurological disorders (and especially spinal cord injuries) have a 25-85 per cent lifetime risk of developing a pressure injury such as that one. However, the authors cannot rule out that the immunosuppression required for the study protocol contributed to the ulcer and infection.
I will keep an eye out for data from Phase II as it rolls in!
Additional recommendations
Modified human mesenchymal stromal/stem cells restore cortical excitability after focal ischemic stroke in rats. So many headlines about this paper – a great addition to your reading list!
Japanese researchers test pioneering drug to regrow teeth. Particularly excited about this one. Imagine a world where losing an adult tooth isn’t a big deal; no more implants, no more bridges – just grow yourself a new one.
Candidate stem cell isolation and transplantation in Hexacorallia. Regenerative medicine… for corals. It still counts.
Black and Asian cancer patients less likely to survive UK stem cell transplant than white peers. This piece in The Guardian covers the following research paper: The impact of patient ethnicity on haematopoietic cell transplantation outcome: a retrospective cohort study on the UK experience
Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages. See Krystal Jacques’ upcoming coverage of this story for Signals!
Pluripotent stem-cell-derived therapies in clinical trial: A 2025 update.
Synthetic organizer cells guide development via spatial and biochemical instructions.
Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals.
Intermittent fasting triggers interorgan communication to suppress hair follicle regeneration.
Maternal gut microbiota influence stem cell function in offspring.
Self-organization of the hematopoietic vascular niche and emergent innate immunity on a chip.
Refractory myasthenia gravis treated with autologous hematopoietic stem cell transplantation.
Suppression of thrombospondin-1–mediated inflammaging prolongs hematopoietic health span.
Systemic factors associated with antler growth promote complete wound healing.
MRI-guided focused ultrasound for treating Parkinson’s disease with human mesenchymal stem cells.
Investigation of the osteogenic effects of ICA and ICSII on rat bone marrow mesenchymal stem cells.
Advancing ex vivo functional whole-organ prostate gland model for regeneration and drug screening.
OpenAI has created an AI model for longevity science.
Molecular and cellular dynamics of the developing human neocortex.
Bone marrow niches orchestrate stem-cell hierarchy and immune tolerance.
Long-range Atoh1 enhancers maintain competency for hair cell regeneration in the inner ear.
Years after donating a kidney, Alabama woman receives one from a pig.
Extracellular fluid viscosity regulates human mesenchymal stem cell lineage and function.
Baby with spina bifida has promising future after fetal surgery with stem cells.
Stem cell therapy for knees 2025: fact-check, costs, risks.
Updated 2025 List of FDA-Approved Cell and Gene Therapies.
Regenerative properties of bone marrow mesenchymal stem cell derived exosomes in rotator cuff tears.
Exosomes Are Being Hyped as a ‘Silver Bullet’ Therapy. Scientists Say No.
Industry updates from the field of stem cell research and regenerative medicine in December 2024.
Metabolic Reprogramming of Neural Stem Cells by Chiral Nanofiber for Spinal Cord Injury.
Delivery of Prime editing in human stem cells using pseudoviral NanoScribes particles.
This Next Generation IVF Startup Facilitated The Birth Of A Baby For The First Time.
Stroke-induced neuroplasticity in spiny mice in the absence of tissue regeneration.
Myoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injury.
Stem-cell therapy during Kasai effective, safe in biliary atresia: Trial.
Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells.
Attenuation of skin injury by a MARCO targeting PLGA nanoparticle.
Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis.
An injury-induced mesenchymal-epithelial cell niche coordinates regenerative responses in the lung.
The World’s First Crispr Drug Gets a Slow Start.
Aurion’s regenerative eye disease med improves vision in phase 1/2 trial.
Spatial transcriptomic clocks reveal cell proximity effects in brain ageing.
Oscillatory fluid flow enhanced mineralization of human dental pulp cells.
The nuclear matrix stabilizes primed-specific genes in human pluripotent stem cells.
NAC regulates metabolism and cell fate in intestinal stem cells.
Timely TGFβ signalling inhibition induces notochord.
Mesenchymal Stem Cells-Derived Extracellular Vesicles for Osteoporosis Therapy.
Lentiviral Gene Therapy with CD34+ Hematopoietic Cells for Hemophilia A.
Other notable FDA approvals and RMATS
FDA approves Humacyte’s off-the-shelf artery implant for vascular trauma repair.
FDA approves mini version of RECELL GO for smaller wounds.
Lyla El-Fayomi
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