“Scientists have developed a tiny scaffold of stem cells to fill holes in the brain caused by stroke,” BBC online has reported. The website says that within a week, tiny biodegradable balls loaded with stem cells have replaced areas of damaged tissue in mouse brains. But the BBC cautions that “there is still a long way to go in stem cell therapy for stroke survivors”.
The laboratory study underpinning this story has further refined the technology behind microscopic, biodegradable “scaffolds”, which could potentially be used to carry neural stem cells to the site of stroke-related brain damage following stroke. MRI imaging was also used to ensure that the particles were delivered to the correct place, and to assess the effects of the grafts over time.
This technology has been tested in mice, and there are still questions about the long-term viability of these grafts, which have no blood supply. It is also possible that there might be negative effects from the scaffold material breaking down in the brain. However, this work will be of great interest, and it sets new directions for further research. More testing and refinement of the technology will be needed before studies in humans are conducted, and before any potential for treating humans brain damage is truly understood.
Dr Ellen Bible and colleagues from Kings College London and the University of Nottingham carried out this laboratory study. The work was supported by a Biotechnology and Biological Sciences Research Council project grant and the Charles Wolfson Charitable Trust Foundation. The study was published in Biomaterials, the peer-reviewed science journal.
This was a laboratory study investigating the use of a microparticle scaffold to deliver neural stem cells into brain cavities caused by tissue damage.
A stroke occurs when blood supply to the brain is disrupted, leading to disintegration of brain tissue and areas of damage, which can often affect brain function. This damage to brain tissue often results in a cavity. Studies in animals have shown that some function can be recovered by transplanting neural stem cells into the region of stroke damage, but recovery is never complete and some cavity remains.
The researchers hypothesised that neural stem cells might improve tissue repair in the damaged area if they have structural support in the cavity, rather than simply being introduced in a cell mixture. Their challenge was to improve the design of existing scaffolds made from PLGA [poly(D,L-lactic acid-co-glycolic acid)] and to investigate the effects of these scaffolds carrying neural stem cells into the brains of mice that had suffered strokes.
There were several parts to the researchers’ experiment. Firstly, they optimised the development of very small PGLA particles that could carry stem cells. They maximised cell attachment by depositing particular chemicals on the surface of the particles investigating how well they carried neural stem cells.
In the second part of the experiment, the researchers examined the effects of stem cell scaffolds on mouse brain cells in culture. In the third part of their investigation, they injected the stem cell-loaded scaffolds into the brains of mice that had experienced stroke-like damage.
Brain imaging was used to guide the insertion of the scaffolds and to assess the impact of these on the brain lesions over time. After imaging, the mice were humanely killed and their brains were sliced and dissected.
At one day after transplant, stem cells were seen either in the middle of the lesion or at the edge. Some cells had migrated into surrounding tissue.
While the stem cells were initially structured as a tightly packed mass of cells, these became more dispersed and web-like over time. Researchers found that the scaffold particles allowed stem cells to migrate, while simultaneously providing them with structural support to encourage integration with tissue at the edge of the lesions. Differentiation of the stem cells into neural cells was evident, and although there was some inflammation in the region, this only seemed to occur at the edges of the lesion.
Importantly, the researchers say that there was no evidence of any blood supply developing around the graft, so the long-term survival of these newly forming cells is questionable. To guarantee survival, small blood vessels must be present.
The researchers say they have demonstrated that suitable scaffold particles can be successfully manufactured, and that these scaffolds have been shown to attach neural stem cells. They also conclude that they have determined the optimum size for these particles, to ensure that the greatest density of stem cells can be carried.
The researchers add that they have used imaging to develop systems to ensure that the scaffold particles are precisely delivered into the brain lesion and to understand the impact of the scaffolds over time.
The researchers say that in order to overcome the problem of blood supply to the graft, they could develop particles that transport substances that would encourage extension of blood vessels (angiogenesis).
This set of laboratory studies sheds more light on the potential application of microparticle scaffolds to carry stem cells to regions of cellular damage. The researchers have refined the PLGA stem-cell delivery system, using brain imaging to ensure appropriate delivery of stem cells and to monitor progress of stem cell transplants in the mice with stroke-like damage. However, it is still early-stage research.
The scientists say that it is important to examine whether the degradation of PLGA particles or their longer term presence in brain tissue has any negative effects on brain cell function and behaviour. Although there was no evidence of this in their study, they only examined mice up to one month after transplantation.
Another important point is the establishment of a blood supply to the grafted tissue. The researchers speculate on ways that this may be achieved, i.e. through the use of VEGFs (chemicals that encourage growth of blood cells), but this has not been tested in this study.
This important research does indeed “bring new hope to patients suffering from stroke and other debilitating neurological conditions”, but any human application is some time away. Further laboratory studies and rigorous human testing of potential treatments must come first.