Enzyme biofactories to enhance cord blood transplants

October 22, 2020

A new way of producing an enzyme called fucosyltransferase VI (FTVI) in the lab could help enhance the therapeutic potential of cord blood transplants.

Cord blood is currently used to treat more than 80 life-threatening conditions, ranging from cancer and immune deficiency to metabolic and genetic disorders. The therapy is predicated on the idea that stem cells in the cord blood will traffic to the bone marrow, where they can help rebuild a healthy blood and immune system that has been damaged by disease. But cord blood stem cells are not naturally adept at this process--which is why several drugmakers have turned to FTVI as a way of enhancing the cells' homing ability.

FTVI is an enzyme involved in tagging cells with sugar molecules in a way that alters migration patterns in the body. In clinical trials, cord blood stem cells treated with FTVI showed enhanced engraftment following infusion into cancer patients. Yet most commercial sources of FTVI available today have only limited enzymatic activity. Plus, they tend to be made using various expression systems that either produce enzymes with low activity or are costly and generate low yields.

Seeking a better manufacturing platform, a team led by Jasmeen Merzaban at KAUST engineered yeast cells and silkworm larvae to express the human version of FTVI. Working with collaborators in Japan, KAUST researchers from several teams came together to devise a purification scheme for obtaining the enzyme at high yields; they then tested how efficiently the end-product could alter human stem cells.

The researchers showed that their yeast- and silkworm-derived FTVI far outperformed commercial sources of the enzyme made in standard expression systems. "Now, these enzymes can be used ex vivo on stem cells to enhance their migration toward the bone marrow during a transplant," Merzaban says.

Alternatively, researchers could take advantage of the new yeast- and silkworm-produced FTVI for drug screening efforts. First author of the study, Asma Al-Amoodi, points out that many metastatic cancers exhibit enhanced activity of FTVI and similar enzymes. "We could envision using such enzymes to screen for small molecule inhibitors that block metastasis," she says.
-end-


King Abdullah University of Science & Technology (KAUST)

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.