New blood vessels from human stem cells
doi:10.1038/nindia.2013.93 Published online 17 July 2013
A new technique to repair damaged blood vessels promises to bring new hope to diabetics. Many diabetes patients end up with damaged blood vessels in their limbs leading to traumatic limb amputations. The new technique developed by a joint research team from the US and India has been successful in growing new blood vessels in mice.
The researchers used endothelial cells (ECs), a type of blood vessel-forming cells isolated from human induced pluripotent stem cells (hiPS) from healthy donors. The hiPS have potential to grow into different types of cells.
"The ability to regenerate or repair blood vessels could make a crucial difference in the treatment of cardiovascular diseases and other conditions caused by blood vessel damage, such as the vascular complications of diabetes, particularly type 2 diabetes," Rekha Samuel, a co-author of the study from Centre for Stem Cell Research, Christian Medical College, Vellore, told Nature India.
In earlier studies, the same group of researchers had used cord blood-derived endothelial precursor cells (EPCs) or human embryonic stem cells (hESCs) to form blood vessels with the help of supporting cells known as mesenchymal precursor cells.
There have been ethical issues concerning the use of hESCs. Besides, the chance of accessing the patient's own cord blood is remote. The discovery of hiPS provided a potential inexhaustible source of vascular cells that can avert such immunological and ethical concerns.
However, the potential of hiPS-derived ECs had not yet been explored in a noninvasive animal model. So the researchers isolated a special kind of hiPS cell lines that express three marker proteins (CD34, KDR and NRP1). They isolated these stem cells from healthy human donors.
These hiPS with specific markers have a potential to form EPCs that ultimately form ECs. But the team found that hiPS-derived ECs alone cannot form new blood vessels. The ECs need help from a type of supporting cells called mesenchymal precursor cells (MPC) from mice to form new blood vessels.
Therefore, they co-implanted hiPS-derived ECs with MPCs in immunodeficient mice. After a couple of weeks, stable vascular networks were prominent. Microscope-aided analyses showed that the engineered vessels demonstrated red blood cell (RBC) velocity and flux comparable to capillaries and exchange vessels in the adjacent mice brain tissues.
Four weeks after implantation, 68% of the mice formed functional blood vessels. Five of these mice had RBC velocities comparable to those of normal capillaries. The engineered vessels lasted 280 days in mice.
To test the feasibility of using this in a disease model, the researchers isolated similar hiPS cells from patients of type 1 diabetes. They co-implanted such hiPS-derived ECs with MPCs in mice with weak immune system. After two weeks, the engineered tissues from patients formed clear vascular networks and such vessels showed good perfusion of red blood cells up to four months.
"In addition, in the disease model, the engineered vessels were not leaky," Samuel says.
These vascular cells will have broad applications in regenerative medicine since blood vessels are essential for any functional organs as recently shown in the generation of functional liver in mice, Samuel says.
- Samuel, R. et al. Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells. P. Natl. Acad. Sci. USA (2013) doi: 10.1073/pnas.1310675110