“There’s a very good chance that this study will eventually have a major impact on many disorders that afflict humankind,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal where the study is published. “These scientists have basically used the body’s repair mechanisms to make new tissues through bioengineering. In years to come, starfish and salamanders will have nothing on us!”
A new method discovered by Yale scientists could be a major milestone in the science of human tissue regeneration and engineering. Because of their discovery, new evidence is provided to support a major shift in the paradigm of the accepted science of tissue engineering from the concept that cells added to a graft pre-implantation are the building blocks of tissue, to a new concept that engineered tissue constructs can actually mobilize the body’s own reparative mechanisms. This includes complex tissue regeneration.
“We believe that through an understanding of human vascular biology, coupled with technologies such as tissue engineering, we can introduce biological grafts that mimic the functional properties of native vessels and that are capable of growing with the patients,” said Christopher K. Breuer from Yale University School of Medicine.
Breuer and colleagues conducted a three-part study in mice, beginning with two groups. The first expressed a gene that made all its cells fluorescent green. The second was normal.
The first part of the study involved extracting bone marrow cells from the mice that expressed green cells, the researchers added them to previously designed biodegradable scaffolds. They then implanted the grafts into the normal mice. The bone marrow-derived mononuclear cells (BMMCs) improved the performance of the graft, but there was a rapid loss of green cells. The cells developed in the new vessel wall were noted to be normal. This suggests that the seeded cells promoted vessel development but they did not turn into vessel wall cells themselves.
In the second part of the study, the team tested whether the cells produced in the host’s bone marrow might be a feasible source for new cells. They replaced the bone marrow cells of a female mouse with those of a male mouse before implanting the graft into a group of female mice. The new vessel was formed by cells of the female, so they did not come from the male bone marrow cells.
The final section of the study involved implanting a segment of vessel from the male attached to the scaffold into a female host. They then found that the side of the graft next to the male segment developed with male vessel wall cells while the side attached to the female host’s vessel formed from female cells. This proves that the cells in the new vessel must have migrated from the adjacent normal vessel. Breuer and his colleagues demonstrated that bone marrow is not a significant source of endothelial or smooth muscle cells that comprise the neovessel and that the adjacent vessel wall is the main source of these endothelial and smooth muscle cells that form 93% of proximal neotissue.
These findings have important implications regarding fundamental mechanisms underlying neotissue formation; in this setting, the tissue-engineered construct functions by mobilizing the body’s innate healing capabilities to “regenerate” neotissue from preexisting committed tissue cells.
“New Method for Engineering Human Tissue Regeneration.” Science Daily. Science Daily LLC, 13 May 2011. Web. 17 May 2011. http://www.sciencedaily.com/releases/2011/05/110512161932.htm.