|Scientists have been able to recreate a subtype of white blood cells called T cells that are important in our body’s defenses against infection / Photo by Shutterstock.com|
Scientists have been able to recreate a subtype of white blood cells called T cells that are important in our body’s defenses against infection. Human T cells seek and destroy cells that have become cancerous or infected with germs. The creation of the synthetic version of T cells can pave the way for the production of drugs that are more effective in treating autoimmune diseases and even cancer. It also will help scientists gain more knowledge about the behavior of human immune cells.
The findings were published in the journal Advanced Materials.
A team effort
Led by Dr. Alireza Moshaverinia, an assistant professor of prosthodontics at the UCLA School of Dentistry, the research team was composed of scientists from the dental school, the UCLA Samueli School of Engineering, and the department of chemistry and biochemistry in the UCLA College. They were able to produce artificially made T cells that function as real human blood cells, able to boost a host’s immunity by signaling to other cells to initiate activation and regulation, thus producing an inflammatory response to the foreign invader.
"The complex structure of T cells and their multifunctional nature have made it difficult for scientists to replicate them in the lab," Moshaverinia said in an article published in Science Daily. "With this breakthrough, we can use synthetic T cells to engineer more efficient drug carriers and understand the behavior of immune cells."
Natural T cells are said to be difficult to use in research because they're very delicate, and their survival lasts only days after being extracted from humans and other animals.
"We see this study's findings as another tool to attack cancer cells and other carcinogens," said Mohammad Mahdi Hasani-Sadrabadi, an assistant project scientist at UCLA Samueli.
Until recently, bioengineers hadn't been able to mimic the complex nature of human T cells. But the UCLA researchers were able to replicate their shape, size, and flexibility, which enable these cells to perform their basic functions of targeting and homing in on infections.
Moshaverinia said other scientists can use the same process to create various types of artificial cells, such as natural killer cells or macrophages, for research on specific diseases or to find treatment.
Then in the future, this approach can help scientists develop a database of a wide range of synthetic cells that mimic human cells.
Natural T cells play a key role in the immune system. They are very smart and adaptive, but much more complex to mimic. They first mature in the thymus gland in the neck. When infection enters the body, they flow through bloodstreams to reach the infected areas. Because they must squeeze between small gaps and pores, T cells have the ability to deform to as small as one-quarter of their normal size. They also can grow to almost three times their original size, which helps them fight off or overcome the antigens that attack the immune system.
Natural T cells
With the researchers successfully mimicking the shape and function of human T cells, Moshaverinia stated that this may help reduce the use of laboratory animals for conducting clinical researches and drug trials.
To mimic the T cell form, the researchers used a microfluidic system, which focused on the behavior, control, and manipulation of fluids, typically on a sub-millimeter scale. A mixture of mineral oil and alginate biopolymer (a gum-like substance made from polysaccharides and water) created microparticles of alginate, which replicate the form and structure of natural T cells. They then collected the microparticles from a calcium ion bath and adjusted their elasticity by changing the concentration of calcium ions in the bath.
To give the synthetic cells the same abilities as their natural counterparts, the researchers coated the synthetic T cells with phospholipids to copy human cellular membranes. Then, using a chemical process called bioconjugation, they linked the T cells with CD4 signalers, the particles that activate natural T cells to attack infection or cancer cells.
Once they had created T cells with the proper physical properties, the researchers needed to adjust the cells' biological attributes to give them the same traits that enable natural T cells to be activated to fight infection, penetrate human tissue, and release cellular messengers to regulate inflammation.
Moshaverinia pointed out that in regular immunotherapy, the patient’s own immune cells are extracted from the blood, expanded in the laboratory, and modified genetically. They are then and injected back into the patient. Based on the modification, these T cells can circulate through the body and help cure cancer or other diseases.
However, with the new development, researchers no longer need human T cells but can make particles that are fully synthetic and programmed to deliver multiple therapeutics at once.
“We can regulate fate (e.g., degradation) of these particles in order to eliminate any potential unwanted side effects. These synthetic T cells can also be used as a model to better understand physical behavior of natural T cells and help researchers deal with them more effectively,” she added.
|The researchers coated the synthetic T cells with phospholipids to copy human cellular membranes / Photo by Shutterstock.com|
Moshaverinia said the behavior of synthetic T cells in the body also needs to be evaluated in-depth to confirm the possibility of using these particles for clinical applications.
“We are planning to develop and optimize a wide range of artificial cells, including other immune cell types, and see how we can manipulate them to deliver different therapeutic cargos,” said Moshaverinia.
The ability to synthesize such artificial cells can help researchers develop in vitro biomimicry models that could improve their understanding of immune cell behavior and optimize the design of effective drugs for the treatment of illness like cancer and autoimmune diseases.
After engineering cells with the correct physical properties, the team altered the cells to give them the same attributes that enable human T cells to be activated to penetrate tissue and to release cytokines for the control of inflammation.
This breakthrough will eventually lead to further steps in experimentation of other cells in the body, paving the way to promote genetically enhanced tissues. The process will aid in providing a functionally working artificial system committed to fighting diseases and infection.