Singaporean Researchers Develop Faster Protocol To Harvest Secretome From Stem Cells
Researchers from
Nanyang Technological University (
NTU),
Singapore have found an easier way to harvest healing factors ie molecules that promote tissue growth and regeneration, from adult
stem cells.
Currently, scientists 'pre-condition' adult
stem cells to secrete healing factors by putting them in a low-oxygen chamber or by using biochemicals or genetic engineering.
The NTU Team (Credit: NTU)
In lab experiments, the
NTU team of materials scientists and biologists tried mimicking the physical conditions that cells find inside the body and grew a particular type of
stem cells called
Mesenchymal Stem Cells (
MSCs) on a softer surface than is normally used.
Mesenchymal Stem Cells (
MSCs) grown on the softer surface, known as hydrogel, increased their secretion of healing factors, known as the
secretome, compared to normal growing surfaces.
This new method of growing
MSCs on hydrogel, a three-dimensional network of polymers with high water content, could potentially be scaled up for mass production of healing factors by biotech companies.
The research findings were reported 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.
MSCs are present in the human body in many tissues, muscles and organs. When they detect tissue damage, they produce healing factors to speed up repairs.
Past studies by the same team showed that when bioengineered
secretome was applied to mice skin wounds, after five days wounds had closed by an average of 71 percent. Mice which did not have the
secretome applied had wound closures of 60 percent after five days.
The NTU team showed in their latest study that the
secretome improved blood vessel formation by up to 60 percent in a chicken egg (chorioallantoic) membrane model over three days, compared to a chicken egg membrane with no
secretome applied.
The new discovery of the pathway that stimulates MSCs to produce therapeutically active
secretome was made 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 recognised "for their discoveries of how cells sense and adapt to oxygen availability."
Other medical scientists have used this concept of oxygen starvation to artificially stress mscs. This in turn activates a major switch, known as Hypoxia-inducible factor 1-alpha (HIF 1-α), that promotes tissue blood vessel growth and repair.
The researchers from
NTU
took these studies one step further and showed that by adjusting the softness of the hydrogel on which the
MSCs were cultured, to as soft as fat tissue, they could activate the HIF 1-α signalling under normal oxygen conditions, without any additional biological or pharmacological agents.
The team believes that using the materials' stiffness to manipulate
MSCs oxygen-sensing metabolism could be useful in the development of advanced cell culture materials that are able to improve the production and therapeutic potential of the
MSC secretomes. Such a development would be advantageous to the biopharmaceutical companies that are currently exploring the development of new
MSCs-based cell-free therapies.
Prof Tay told
Thailand Medical News, "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."
The research team now plans to study in further detail why biomimicking soft surfaces would cause stress to the
MSCs and aims to translate the use of the biomaterials-engineered
MSCs secretome to the treatment of chronic wounds and vascular diseases in humans.
References:
Haibo Yang Et Al. Materials Stiffness‐Dependent Redox Metabolic Reprogramming Of Mesenchymal Stem Cells For Secretome‐Based Therapeutic Angiogenesis, Advanced Healthcare Materials (2019). DOI: 10.1002/adhm.201900929
Haibo Yang et al. Soft Material Approach to Induce Oxidative Stress in Mesenchymal Stem Cells for Functional Tissue Repair, ACS Applied Materials & Interfaces (2016). DOI: 10.1021/acsami.6b09222
