3D Substrates Recreate An Environment Where Heart Cells Grow Inside the Human Body

Highlights:

• Cardiomyocytes grown in a heart-like environment mature more quickly and with improved functionality when compared to stem cell derived cardiomyocytes.
• The heart-like environment is created by a 3D substrate that recreates the environment in which heart cells grow inside the human body.
• The heart muscle cells grown in these heart molds are also less likely to be rejected by the patient's body.

Growing heart muscle cells in a heart-like environment in vitro allow the cells to mature more quickly and with better functionality, shows new study. The heart like environment is provided by three-dimensional substrates that mimic the natural heart environment. The cells grown in these mold are also less likely to be rejected by the patient's body during transplantation. The study is published in the journal Advanced Functional Materials.

A normal heart beats about 2.5 billion times during the average lifetime of a person. The constant action of contraction and relaxation can sometimes cause strain on the heart muscle resulting in heart problems.

These weak heart muscle cells called cardiomyocytes are usually repaired by injecting healthy cardiomyocytes into the damaged heart muscle. The healthy cardiomyocytes are derived from pluripotent stem cells (PSC). Using biochemical signals these stem cells can be reprogrammed to become any type of cell in the body including heart muscle cells.

The problem with reprograming pluripotent stem cells into cardiomyocytes

Converting PSCs into cardiomyocytes occurs in a two-dimensional setting, usually in petri plates. However, in-vivo, the growth environment plays a large role in the way the cells develop. Due to lack of an appropriate growth environment, PSC derived cardiomyocytes are underdeveloped and do not gain their full potential functionality.

"Unfortunately stem cell therapeutics don't have high success rates partly because the cells are not mature and fully functional. The maturation and functionality are essential," says Parisa Pour Shahid Saeed Abadi, assistant professor of mechanical engineering working on creating heart cell growth environments.

Induced pluripotent stem cell-derived cardiomyocytes using substrates

To provide the right growth environment to PSCs, Abadi and team have developed three-dimensional substrates that create a heart-like environment for the cells. Cardiomyocytes grown in these 3D substrates or molds mature more quickly, have improved functionality and are less likely to be rejected by patients' bodies.

The biomechanical properties of the substrates simulate the actual heart environment; one with lots of pressure and specific forces acting on the growing cells. This pressure leads to more robust cardiomyocytes. Photolithography and re-flow processing were used to pattern the substrates at the micron and submicron levels to approximately resemble the natural physical forces cells experience.

"The mechanical properties of substrates play an important role in the cell behavior because the mechanical cues that cells sense in the actual (heart) environment is unique," Abadi says. "We are using biochemical and biomechanical cues to enhance the differentiation and maturation. If we don't take advantage of the physical cues and only rely on chemical cues, the process suffers from low efficiency and batch-to-batch inconsistency."

The team hopes to improve the substrate preparation methods to stimulate electrical conductivity between cells. Since cardiomyocytes need to communicate with each other during their growth, this inclusion is thought to make the cells closer to cardiomyocytes in vivo.

Reference:

1. Mending broken hearts with cardiomyocyte molds - (http://www.sciencenewsline.com/news/2018031321180056.html)

Source: Medindia