Priming Cocktail for Cardiac Stem Cell Grafts


Approximately 700,000 Americans suffer a heart attack every year and stem cells have the potential to heal the damage wrought by a heart attack. Stem cells therapy has tried to take stem cells cultured in the laboratory and apply them to damaged tissues.

In the case of the heart, transplanted stem cells do not always integrate into the heart tissue. In the words of Jeffrey Spees, Associate Professor of Medicine at the University of Vermont, “many grafts simply didn’t take. The cells would stick or would die.”

To solve this problem, Spees and his colleagues examined ways to increase the efficiency of stem cell engraftment. In his experiments, Spees and others used mesenchymal stem cells from bone marrow. Mesenchymal stem cells are also called stromal cells because they help compose the spider web-like filigree within the bone marrow known as “stroma.” Even though the stroma does not make blood cells, it supports the hematopoietic stem cells that do make all blood cells. ¬†Here is a picture of bone marrow stroma to give you an idea of what it looks like:

Immunohistochemistry-Paraffin: Bone marrow stromal cell antigen 1 Antibody [NBP2-14363] Staining of human smooth muscle shows moderate cytoplasmic positivity in smooth muscle cells.
Immunohistochemistry-Paraffin: Bone marrow stromal cell antigen 1 Antibody [NBP2-14363] Staining of human smooth muscle shows moderate cytoplasmic positivity in smooth muscle cells.
Stromal cells are known to secrete a host of molecules that protect injured tissue, promote tissue repair, and support the growth and proliferation of stem cells.

Spees suspected that some of the molecules made by bone marrow stromal cells could enhance the engraftment of stem cells patches in the heart. To test this idea, Spees and others isolated proteins from the culture medium of bone marrow stem cells grown in the laboratory and tested their ability to improve the survival and tissue integration of stem cell patches in the heart.

Spees tenacity paid off when he and his team discovered that a protein called “Connective tissue growth factor” or CTGF plus the hormone insulin were in the culture medium of these stem cells. Furthermore, when this culture medium was injected into the heart prior to treating them with stem cells, the stem cell patches engrafted at a higher rate.

“We broke the record for engraftment,” said Spees. Spees and his co-workers called their culture medium from the bone marrow stem cells “Cell-Kro.” Cell-Kro significantly increases cell adhesion, proliferation, survival, and migration.

Spees is convinced that the presence of CTGF and insulin in Cell-Kro have something to do with its ability to enhance stem cell engraftment. “Both CTGF and insulin are protective,” said Spees. “Together they have a synergistic effect.”

Spees is continuing to examine Cell-Kro in rats, but he wants to take his work into human trials next. His goal is to use cardiac stem cells (CSCs) from humans, which already have a documented ability to heal the heart after a heart attack. See here, here, and here.

“There are about 650,000 bypass surgeries annually,” said Spees. “These patients could have cells harvested at their first surgery and banked for future application. If they return for another procedure, they could then receive a graft of their own cardiac progenitor cells, primed in Cell-Kro, and potentially re-build part of their injured heart.”

Big Strides in Stem Cell Treatments for Neonatal Lung Diseases


Bernard Thébaud works at the Ottawa Hospital Research Institute (OHRI) and Children’s Hospital of Eastern Ontario (CHEO), and is also a member of the Ottawa Stem Cell Initiative. Dr. Thébaud has proposed a new therapy that utilizes umbilical cord stem cells to treat a lung disease called bronchopulmonary dysplasia (BPD), which was previously thought to be untreatable.

Th√©baud described BPD in this way: “BPD is a lung disease described 45 years ago in which we have made zero progress. And now, with these cord-derived stem cells there is a true potential for a major breakthrough. I am confident that we have the talent and the tools here at CHEO and OHRI to find a treatment for BPD. These findings published today are helping us get there.”

Every year, BPD affects ~10,000 premature newborns in Canada and the US. The lungs of infants with BPD are not developed enough to function properly, and consequently the baby has to be placed on a ventilator in order to receive sufficient quantities of oxygen. Mechanical respirators, however, are very hard on such young, friable lungs, and the lungs then to fray and this prevents them from developing properly. The longer the baby stays in the neonatal intensive care unit, the greater the degree of multiorgan damage (retina, kidneys, and the brain). Therefore, the baby needs oxygen to survive, but the very act of giving them oxygen eventually hastens their death.

Th√©baud’s research team used new-born rats that were given oxygen soon after their premature birth. Some were given stem cell treatments and others were not. These experiments produced five new findings:

1) Mesenchymal stem cells (MSCs) from human umbilical cord can protect the lungs when injected into the lungs as the animals were put on oxygen.
2) MSCs had a tendency to stimulate repair of the damaged lungs when injected two weeks after the animals were put on oxygen.
3) The medium in which the MSCs were grown (conditioned medium) was injected into the lungs instead of the cells, this medium had the same reparative and protective effects as the cells themselves. ¬†This suggests that it is the cocktail of growth factors and other supportive molecules secreted by the MSCs that provide their healing properties. ¬†Such a mechanism, in which the cells secrete molecules that affect nearby cells and tissue, is known as a “paracrine” mechanism.
4) When examined six months after treatment (the equivalent of 40 human years), the treated animals had better exercise performance and more normal lung structure.
5) MSC administration did not adversely affect the long-term health of the laboratory animals. None of the MSC-treated animals had any tumors and MSCs given to control animals that did not have BPD were also normal six months later.

Thébaud would like to conduct a pilot clinical (Phase I) study within two years with around 20 human patients in order to determine if this treatment is feasible and safe. If the treatment turns out to be safe, Thébaud would like to initiate a randomized controlled (Phase II) clinical trial.

See Maria Pierro et al., “Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia,” Thorax 2012: DOI:10.1136/thoraxjnl-2012-202323.