Genetically Engineered Bone Marrow Stem Cells Reverse Ischemic Cardiomyopathy

Muhammad Ashraf is a professor of Pharmacology at the University of Illinois in Chicago.  Dr. Ashraf and his colleagues have published some very fine papers that have examined the ability of stem cells to heal the heart after a heart attack.  Recently, Ashraf’s team examined the ability of a particular population of bone marrow cells, characterized by the presence of the Sca-1 protein on their cell surfaces, to heal the heart after a heart attack.  In particular, Ashraf’s group genetically engineered Sca-1-positive cells to secrete a cocktail of growth factors, and then they tested the ability of such cells to heal a damaged heart.

Sca-1 is a protein that is found on the surfaces of hematopoietic stem cells and other cell types as well.  Therefore, selecting Sca-1 cells will not necessarily give you a pure cell population.  However, such cells can be readily isolated and genetically engineered to make these growth factors.

Ashraf and his coworkers isolated Sca-1 cells from the bone marrow of mice that expressed a glowing green protein.  These cells were then genetically engineered with plasmids (small circles of DNA) to express the growth factors Insulin-like growth factor-1, vascular endothelial growth factor, hepatocyte growth factor, and stromal cell-derived factor-1alpha.  All four of these growth factors have been shown to play supportive roles in the healing of the heart after a heart attack.

When these genetically engineered Sca-1-positive cells were co-cultured with other cells and then grown in low oxygen conditions, the genetically engineered cells prevented the other cells from dying.  The genetically engineered cells are grew faster in culture than their non-genetically engineered counterparts.  When the culture medium in which these genetically engineered cells were grown was used to grow umbilical vein endothelial cells (UVECs), those UVECs showed increased rates of growth.  This suggests that the genetically-engineered Sca-1 cells secreted growth factors into their culture medium and these growth factors are the reason these cell grow faster than non-genetically engineered Sca-1 cells.

When these same cells were injected into the heart tissue of mice that had suffered from heart attacks, they were able to survival over twice as well as non-genetically engineered Sca-1 cells.  When the laboratory animals that received the injections of genetically engineered Sca-1 cells were put down 4 weeks after their stem cell treatments, their hearts were removed, sectioned and examined in detail.  These examinations clearly showed that hearts from those mice that had received injections of genetically-engineered Sca-1 cells had increased blood vessel densities.  There was an additional surprise, since the injected Sca-1 cells were taken from green-glowing mice, they also glowed green.  Green-glowing cells were shown to express Cx43 (the protein that links heart muscle cells together and lets them beat in harmony) and be connected to host heart muscle cells.  This suggests that a bone marrow cell population can actually electrically connect with a heart muscle cell, which is something bone marrow cells are not supposed to be able to do.  Mind you, the number of connected cells was small, and they could be doing this simply as a result of cell fusion.

Additionally, injection of genetically-engineered Sca-1 cells also decreased the infarct size in the hearts of these mice.  The size of the infarct in the treated mice was less than half that of the untreated mice.

This shows that Sca-1 cells from bone marrow have the capacity to augment recovery of the heart after a heart attack, and that this ability is further increased through the co-administration of growth factors.  Using such a system in human patients will require the determination of the precise dosage of these growth factors, since using genetically engineered cells in human patients will probably not be approved in the near future.