Are We Close to a Stem Cell Therapy for Heart Failure?
Discover the potential and progress of cell therapies in cardiology and the technologies leading the way.
Complete the form below to unlock access to ALL audio articles.
Cell therapy is transforming the treatment landscape for many diseases previously believed to be untreatable. While oncology holds the largest market share, today, cell therapies are being explored for a wide range of indications, including autoimmune, neurodegenerative and cardiovascular diseases.
Key advances in the understanding and genetic engineering of cells have led to a series of cell therapy approvals. Despite this, challenges such as cell sourcing, isolation and expansion, as well as the cost and accessibility of these therapies, continue to pose significant challenges.
Dr. Ibon Garitaonandia, MBA, is the chief scientific officer at CellProthera, a clinical-stage biotech developing stem cell therapy for ischemic heart disease. In this article, Garitaonandia discusses some of the challenges of developing cell therapies for cardiology and introduces ProtheraCytes®, a stem cell preparation with the potential to regenerate cardiac tissue.
Cell therapy manufacturing challenges
Cell therapies come with a host of unique challenges that begin with the initial sourcing of the donor cells. “The quality of harvested cells is very important for a successful therapy because factors such as the patient’s age, disease state and comorbid conditions can affect the viability and functionality of the cells,” Garitaonandia told Technology Networks. “There is inherent donor-to-donor variability that can affect the cell yield.”
These challenges continue into the expansion of cells, where maintaining a cell’s regenerative properties and genetic stability is key, requiring precise culture conditions.
“New automated technologies are being developed to improve the yield of cell expansion, enhance the purity and viability of the cell product, reduce variability and increase reproducibility in cell production,” Garitaonandia explained.
In addition, adherence to stringent regulatory standards throughout the production process is vital to ensure the safety and efficacy of the final product. This includes establishing robust production practices that comply with Good Manufacturing Practice (GMP).
“Collaboration between regulatory bodies, industry and academia is key to developing comprehensive guidelines that ensure the quality and safety of cell therapies,” said Garitaonandia.
The inherent complexity of manufacturing cell therapies impacts their cost, and as a result, these life-saving therapies are often limited to a smaller patient population.
“Automation and improved bioprocessing techniques can significantly lower production costs,” Garitaonandia stated. “For instance, at CellProthera, we have developed an automated, closed platform – called the StemXpand system – for GMP-compliant simultaneous expansion of multiple clinical batches. The company has received ISO 13485: 2016 certification for the development of the StemXpand system, which leverages StemPack single-use cell-culture kits and StemFeed medium for optimized CD34+ cell expansion.”
“Additionally, economies of scale achieved through centralized manufacturing facilities can make these therapies more affordable and accessible,” he continued.
Developing a successful stem cell therapy for heart failure
Given these challenges, what does a successful cell therapy for heart disease look like? Garitaonandia states that the critical success factors are the “cell type used, the dose, the route of administration and the patient selection.”
Previous studies have tested the possibility of using stem cell-derived cardiomyocytes; however, this has been shown to cause arrhythmia in animal models. Other cell therapies for acute ischemic heart disease have used bone marrow-derived mononuclear cells, but while this approach has shown promise, the results have been inconsistent. Garitaonandia believes “This is likely due to the fact that they contain a very low percentage of CD34+ cells (0.5–1%). Our therapy is based on administering CD34+ cells, which have angiogenic properties that promote the regeneration of the ischemic lesion.”
Clinical studies, such as the PreSERVE-AMI study, showed that the benefits of CD34+ cells in a post-acute myocardial infarction (AMI) setting are dose-dependent. For example, one study showed that a threshold of 10 million CD34+ cells was required to significantly improve the left ventricular ejection fraction and reduce infarct size.
It’s not just the dosage of the therapy that’s important, but also the delivery method. “Previous clinical studies delivering the cells through the intracoronary and intravenous routes had low retention rates and therefore, inconsistent results,” said Garitaonandia. “The transendocardial injection of CD34+ cells is associated with higher retention rates – up to five times higher retention rate than the intracoronary injection.”
Finally, the right patient population must be chosen. “Administering the therapy shortly after the AMI has been shown to have the best results, because once the lesion becomes fibrotic, it is more difficult to repair. We have also observed that patients with multiple risk factors and the presence of microvascular obstruction are the best responders,” continued Garitaonandia.
New hope for heart attack patients
With these considerations in mind, CellProthera developed ProtheraCytes – stem cells derived from autologous expanded CD34+ cells designed to regenerate damaged tissue following a heart attack.
Galien Forum 2025: A New Era of Collaboration and Patient-Centered Healthcare
At the Galien Forum 2025, experts discussed the future of healthcare, focusing on collaboration and patient-centered care.View Listicle
To manufacture ProtheraCytes, CD34+ cells are harvested from the peripheral blood of the patient after mobilization from the bone marrow. These cells are then purified and expanded using CellProthera’s StemXpand system, ready to be sent to the clinic for injection.
“We have shown that ProtheraCytes secrete paracrine factors that induce angiogenesis and the revascularization of post-ischemic myocardial lesions,” Garitaonandia explained. “These paracrine factors also enhance the proliferation of resident cardiomyocytes, thus reducing fibrosis and attenuating remodeling effects. ProtheraCytes secrete growth factors such as vascular endothelial growth factor and exosomes containing miRNAs with angiogenic, anti-fibrotic, anti-apoptotic and anti-inflammatory properties. ProtheraCytes also have the capacity to differentiate into endothelial cells and promote angiogenesis in vitro and in vivo.”
CellProthera was recently named the winner of an International Society for Cell & Gene Therapy (ISCT) Stem Cell Engineering Abstract Award for its presentation on the positive results of its Phase 1/2b study of ProtheraCytes.
The Phase 2 clinical trial was the first to test transendocardial injection of expanded CD34+ cells in severe AMI patients. CellProthera recruited 33 patients to the ProtheraCytes treatment group versus 16 patients who were included in the standard of care control group. The study’s goal was to test the treatment's safety and evaluate the efficacy profile of ProtheraCytes from randomization to 6-month follow-up.
The results of the trial were positive, Garitaonandia said: “The transendocardial injection of ProtheraCytes was feasible and there were no unexpected serious adverse events related to ProtheraCytes.”
“The treatment may improve remodeling as suggested by favorable changes at 6 months of secondary endpoints.”
The next step for this therapy on the path to market will be a Phase 3 trial in the USA and Europe to evaluate the long-term effects of ProtheraCytes versus the standard of care in a post-AMI setting. The company recently announced a partnership with CELLforCURE by SEQENS, as its contract development and manufacturing organization partner for the Phase 3 trial.
