A team of scientists has been able to engineer “stable and functional” blood vessels in mice using induced pluripotent stem (iPS) cells taken from humans. The blood vessels lasted for 280 days in the brain of the mice. The scientists are from Massachusetts General Hospital, Boston, and Harvard Stem Institute, Harvard University.
The skin cells of healthy people and those with Type I diabetes were used to produce iPS cell lines, and, in turn, the blood vessels. The results of the study are published online on July 16 in the Proceedings of the National Academy of Sciences (PNAS) journal.
This work is proof of concept demonstration that vascular precursor cells — endothelial precursor cells and mesenchymal precursor cells from iPS cells — can be used to engineer blood vessels. While endothelial cells form the inner lining of blood vessels, mesenchymal cells provide structural stability.
3 specific markers
“The method of deriving these two cells from iPS cells was by using three specific markers. The way we did it enabled us to engineer blood vessels in vivo [inside the mice] using sophisticated microscopy and mouse models,” said Dr. Rekha Samuel, Professor of Pathology at the Centre for Stem Cell Research, CMC, Vellore, Tamil Nadu. She was in Boston as a post-doctoral fellow in Dr. Rakesh K. Jain’s (one of the co-authors) laboratory with a DBT fellowship.
Clinical applications will become possible only once the safety and body’s immune response to the lab-created vessels are studied in detail.
To begin with, the two precursor cells (endothelial precursor cells and mesenchymal precursor cells) are mixed in a particular material in the lab. “This proteinaceous material provides the environment for the two cells to grow and connect in a dish,” explained Dr. Samuel. “This is called engineered construct.”
The engineered construct was then transferred onto the brain and dorsal skin of the mice and visualised with a microscope through a glass cover slip. It was also subcutaneously injected into the backs of the animals. The mice with subcutaneously injected construct were sacrificed (killed) after two weeks. Even within this short period, it had formed blood vessels and connected with the animals’ vessels. The presence of mouse RBCs in the engineered vessels is proof that blood had flowed through them.
More permeable vessels
“We were able to study the construct in the brain non-invasively every day for 280 days,” she said. “It allowed us to measure the functionality of the construct and understand the differences between the vessels of the host and the construct.” For instance, the engineered vessels were more permeable compared with vessels of the mice. In the case of skin, the construct was studied for 30 days. “Endothelial cells are different in different organs. [Hence], vessels with organ-specific endothelial cells are needed,” stressed Dr. Samuel. “So we need the best way to create the vessels to make it translational [taking it to clinical use].”
This study holds great promise to restore blood flow, especially in the case of Type II diabetic patients with ischemia in the foot. According to her, about 20 patients with diabetic foot problems are seen per week at CMC, of which, four end up in amputation.