A simple way to obtain regenerative factors of stem cells in the laboratory has been found

A research team from Nanyang Technological University (NTU), Singapore, has found a simple way to isolate therapeutic factors (molecules that promote tissue growth and regeneration) from adult stem cells.

Currently, scientists are preparing mature stem cells to isolate regenerative factors by placing them in a low-oxygen chamber, as well as using biochemical methods and genetic engineering.

NTU researchers in their laboratory experiments tried to mimic the physical conditions in which cells are in the body. In a new work, scientists used mesenchymal stem cells (MSCs) grown on a hydrogel, which was a softer surface than is usually used in similar techniques.

Under such conditions, there was a significant increase in the production of MSC factors, compared with stem cells cultured on conventional growth surfaces.

This method of growing MSCs on a hydrogel, a three-dimensional structure consisting of polymers with a high water content, can potentially be used for mass production of regenerative factors by biotechnological companies.

The results were published in Advanced Healthcare Materials by a multi-disciplinary team comprising NTU Assistant Professor Dalton Tay from the School of Materials Science and Engineering, and NTU associate professors Andrew Tan from the Lee Kong Chian School of Medicine and Newman Sze from the School of Biological Sciences.

In the human body MSCs are present in various tissues and organs. Their characteristic feature is the ability to find the damage zone and secrete biologically active products (secretome), in particular, various growth factors and cytokines, promoting regeneration.

Earlier studies of the same group showed that when using an artificially created secretome to heal skin lesions in mice, wounds were tightened by an average of 71% after five days. In the control group of animals that did not receive secretome treatment, wounds healed by 60% over the same time period.

In a recent study, the NTU group showed that secretome improved blood vessel formation by 60% in the membrane (chorioallantois) of a chicken egg over three days compared to the membrane of a chicken egg without treatment with the secretome.

The mechanism that stimulates the production of the therapeutically active MSC secretome was identified by the winners of the 2019 Nobel Prize in Physiology or Medicine, Dr. William G. Kaelin Jr, Sir Peter J. Ratcliffe and Prof Gregg L. Semenza, who were recognized “for their discoveries of how cells sense and adapt to oxygen availability”.

Other scientists have used this concept of oxygen starvation to create artificial stress for MSCs. This activates the main switch, known as the hypoxia-inducible factor 1-alpha (HIF 1-α), which promotes the growth and restoration of blood vessels in the tissue.

NTU scientists have improved on these studies and have shown that by adjusting the softness of the hydrogel on which MSCs are cultured so that it is as soft as adipose tissue, it is possible to activate the transmission of HIF 1-α signals under normal conditions of oxygen content, without any additional biological or pharmacological agents.

Researchers believe that using the rigidity of materials to manipulate the oxygen-sensitive metabolism of MSCs may be useful in developing advanced cell culture materials that can improve the production and therapeutic potential of MSCs secretome. Such a development would be beneficial for biopharmaceutical companies, which are currently studying the development of new cell-free treatments based on MSCs.

“Our goal is to make MSCs produce the same healing factors in the lab as they do in the body during tissue repair, and that these might then be made into serums or incorporated into tissue patches that when applied to injuries, would increase the speed of healing”, – said Prof. Tay.

The team now plans to look more closely at the reason why soft-surface biomimicry would cause stress in mesenchymal stem cells. Also, scientists intend to use MSCs secretome, created with the help of biomaterials, in the treatment of chronic wounds and vascular diseases in patients.