John Murphy, MDLinx, 09/28/2015
Researchers have developed a stem-cell loaded hydrogel that sticks for days to the wall of a beating heart. The hydrogel acts as a “synthetic stem cell niche” for accelerating tissue repair after myocardial infarction, according to a study published online September 4, 2015 in Biomaterials.
Although stem cell therapy offers the promise of “organ repair on demand,” using stem cells in the heart itself has not yielded much success because very few of the transplanted cells survive, said the study’s corresponding author M. Roselle Abraham, MBBS, MD, assistant professor of medicine at the Johns Hopkins University School of Medicine and medical director of the Johns Hopkins Hypertrophic Cardiomyopathy Center of Excellence, in Baltimore, MD.
Earlier experiments that injected stem cells into the heart wall showed that, when the heart beats, the cells are pushed out into the lungs before they get a chance to adhere to the wall, Dr. Abraham said.
Additionally, stem cells don’t survive long out of culture—their metabolism slows, causing them to die in several hours unless they are given the opportunity to attach to tissue.
“If we could inject fewer cells soon after heart attacks and coax them to proliferate following transplantation, we could limit scar formation and be more successful with re-growing new heart muscle.” Dr. Abraham said.
In this investigation, the researchers developed a novel “metabolic scaffold” that prevents stem cells from being pumped out of the heart while also promoting their viability for days, not just hours.
The cardio researchers teamed with biomedical engineers in the Translational Tissue Engineering Center at Johns Hopkins University School of Medicine to develop a hydrogel that combines serum with hyaluronic acid. By mixing these two components, the researchers created a sticky gel that functions as a synthetic stem cell niche—it encapsulates stem cells while nurturing them and rapidly restoring their metabolism.
In vitro testing showed that stem cells encapsulated in the hydrogel not only survived at levels near 100% but proliferated and thrived for days. The stem cells in hydrogel also showed markedly higher production of growth factors involved in cardiac regeneration, when compared with stem cells suspended in a solution.
Next, the researchers injected the stem cell-hydrogel into the beating hearts of living rats and found that about 73% of the cells were retained after an hour, compared with 12% of stem cells that were suspended in solution. Over the next 7 days, the number of regular solution-based stem cells continued to decline while stem cells in the hydrogel increased in number, resulting in a higher density of blood vessels.
In rat models of heart attack damage, the hydrogel-based stem cells improved pumping efficiency of the left ventricle by 15% after 4 weeks, compared with 8% from stem cells in solution. Even injections of the hydrogel on its own significantly improved heart function and increased the number of blood vessels in the region of the heart attack, the researchers found.
These results show that the stem cell-hydrogel is an ideal candidate for clinical translation in humans, the authors concluded.
Researchers have developed a stem-cell loaded hydrogel that sticks for days to the wall of a beating heart. The hydrogel acts as a “synthetic stem cell niche” for accelerating tissue repair after myocardial infarction, according to a study published online September 4, 2015 in Biomaterials.
Although stem cell therapy offers the promise of “organ repair on demand,” using stem cells in the heart itself has not yielded much success because very few of the transplanted cells survive, said the study’s corresponding author M. Roselle Abraham, MBBS, MD, assistant professor of medicine at the Johns Hopkins University School of Medicine and medical director of the Johns Hopkins Hypertrophic Cardiomyopathy Center of Excellence, in Baltimore, MD.
Earlier experiments that injected stem cells into the heart wall showed that, when the heart beats, the cells are pushed out into the lungs before they get a chance to adhere to the wall, Dr. Abraham said.
Additionally, stem cells don’t survive long out of culture—their metabolism slows, causing them to die in several hours unless they are given the opportunity to attach to tissue.
“If we could inject fewer cells soon after heart attacks and coax them to proliferate following transplantation, we could limit scar formation and be more successful with re-growing new heart muscle.” Dr. Abraham said.
In this investigation, the researchers developed a novel “metabolic scaffold” that prevents stem cells from being pumped out of the heart while also promoting their viability for days, not just hours.
The cardio researchers teamed with biomedical engineers in the Translational Tissue Engineering Center at Johns Hopkins University School of Medicine to develop a hydrogel that combines serum with hyaluronic acid. By mixing these two components, the researchers created a sticky gel that functions as a synthetic stem cell niche—it encapsulates stem cells while nurturing them and rapidly restoring their metabolism.
In vitro testing showed that stem cells encapsulated in the hydrogel not only survived at levels near 100% but proliferated and thrived for days. The stem cells in hydrogel also showed markedly higher production of growth factors involved in cardiac regeneration, when compared with stem cells suspended in a solution.
Next, the researchers injected the stem cell-hydrogel into the beating hearts of living rats and found that about 73% of the cells were retained after an hour, compared with 12% of stem cells that were suspended in solution. Over the next 7 days, the number of regular solution-based stem cells continued to decline while stem cells in the hydrogel increased in number, resulting in a higher density of blood vessels.
In rat models of heart attack damage, the hydrogel-based stem cells improved pumping efficiency of the left ventricle by 15% after 4 weeks, compared with 8% from stem cells in solution. Even injections of the hydrogel on its own significantly improved heart function and increased the number of blood vessels in the region of the heart attack, the researchers found.
These results show that the stem cell-hydrogel is an ideal candidate for clinical translation in humans, the authors concluded.