Stem cell patch advances

28th June 2016

Posted By Paul Boughton

The collagen cell carrier consists of a dense network of long, intact collagen type I fibres from bovine skin. As a stable, biocompatible matrix it immobilises therapeutic stem cells at infarcted heart tissue

Dr Jessica Daecke reports on how stem cell patches could represent a new therapy for heart diseases

Chronic ischemic cardiac diseases such as heart infarction can today be treated only paselliatively but there is no therapy available that restores function that has been lost. Cell-based therapeutic approaches, carried out by injection of stem cells into the heart suggest beneficial effects on cardiac function but are still hampered by the quick loss of the injected cells from the region of damage within hours.

Now a cooperation of academia and industry partners in Germany and Spain brings forward an enhanced solution to immobilise therapeutic adipose-derived stem cells (ADSCs) cells at the site of damage: by seeding on a thin and highly biocompatible collagen membrane that can be sutured directly to the heart muscle. 

The impacts of this advanced therapy medicinal product (ATMP) were investigated in a rat and a preclinical swine model for chronic myocardial infarct. “One week after suturing the collagen cell carrier loaded with ADSCs to the site of damaged cardiac tissue, one quarter of cells had engrafted in the heart muscle, while in the group where ADSCs had been administered by injection, implanted cells were lost completely,” says Felipe Prosper of the University of Navarra. “And most importantly, after four months the volume of blood pumped from the heart ventricle had increased by 15% - significantly more than in the control groups.”

The researchers ascribe the improved heart function to several effects. Firstly, they observe enhanced vascularisation near the infarcted zone. Secondly, cardiac tissue remodelling, usually occurring after infarction and leading to stiff, fibrotic tissue is reduced significantly, the mechanical behaviour resembling healthy hearts.

These positive effects are assumed to be caused by secretion of proteins by the ADSCs that stimulate regenerative processes in the damaged tissue. Though this paracrine mechanism has also been related to other types of stem cells, ADSCs represent an abundant and well accessible source of adult stem cells and, for the cooperation partners, are best suited to further analyse and define cell qualities relevant for cardiac therapy.

Unique characteristics

The distribution of secreted factors to the region where they are required is favoured by unique characteristics of the collagen cell carrier (CCC) used as carrier for these ADSCs that set it apart from other collagen products: 

* Low thickness (20µm)

* Good permeability

* Tear resistance and high elasticity to enable suturing and adaptation tightly to the pumping heart.

These pre-requisites ensure a minimal and barrier-free distance between ADSCs and the injured tissue. 

When compared with chemically cross-linked and thus stiffer material, it was also observed that the CCC underwent a timely and smooth biodegradation process. Importantly, it triggered only a mild inflammatory reaction that was even lower than for the suturing material used to fix the membrane.

But Dr. Prosper’s group found that the CCC may not only offer “passive” favourable conditions to let the ADSCs do their job. “Just by culturing ADSCs on the collagen membrane we observed an altered gene regulation that may ultimately lead to the beneficial effect on unwanted cardiac tissue remodelilng.” For this, the interaction with the CCC may positively influence ADSC signalling and- secretion for this therapeutic purpose.

The improved cell engraftment and presumably favourable composition of ADSCs secretion mediated by the collagen carrier drastically reduced the number of cells required for implantation. Accordingly, 50 million ASDCs were sufficient to gain positive outcome. Therefore the hazard of unwanted cell spreading to other organs and the adverse risks related such as tumorigenesis are minimised, which are important issues in cell-based therapies.

“These very promising results persuaded us to build up a facility to produce CCCs under strictly controlled clean room conditions in medical grade quality and to proceed now to clinical studies. This new facility will contribute to the clinical development of this and other ATMPs as well as enable the improvement of medical devices in cooperation with existing partners,” says Lluís Quintana from Viscofan BioEngineering, the company developing special collagen products for R&D and now advancing towards the medical market. 

“Together with our partners we envision a real regenerative therapy for patients suffering from chronic cardiac dysfunction resulting from an infarct. By regenerating heart pumping function the quality of life can be significantly improved – leading to less fatigue, more activity, higher patient independence and ideally less mortality related to cardiac insufficiency,” Quintana states. “Our studies will also hopefully bring forward the field of ATMPs, which is currently underrepresented due to high economical risks, complexity of the products and lack of predictable and clear regulatory guidance. By advancing this therapy and by developing similar approaches for other medical indications we intend to contribute to turn Europe into a point of reference in regenerative medicine.”

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Dr Jessica Daecke is with Viscofan BioEngineering

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