June 12, 2012

As stem-cell-based therapies become the standard of care for a wide variety of diseases, improved freezing-based preservation techniques, or cryopreservation, will be necessary to increase patient access, reduce cost and enhance the safety and effectiveness of human adult stem cells. Over the last 20 years, the area of proteomics, or the study of proteins, has informed the field of stem cell research. In other words, cells are not just cells. The conditions stem cells are placed in, and the proteins they subsequently express, radically affect how they behave. Two LSU researchers are linking the fields of proteomics and stem cell biology to the field of cryopreservation in order find clues to what proteins are important in helping stem cells better survive the freezing process.

LSU Associate Professor and Louisiana Land & Exploration Company Endowed Professor of Mechanical Engineering Ram Devireddy along with Professor Jeff Gimble at the Pennington Biomedical Research Center recently received a National Institutes of Health, or NIH, grant of $370,000 to pursue a novel line of research in adipose-derived stem cell cryopreservation. This research focuses on the investigation of new protocols and protein expression states that would help stem cell therapy products such as engineered bone implants survive the freezing process required to store and ship these products.

Currently, stem cells have a relatively short ‘shelf life,’ and limited research exists that explores how freezing and storing processes affect their viability and functionality. “Our goal is to find new ways of storing stem cells such that upon unfreezing, the cells behave just like they did before we froze them,” said Devireddy.

Stem cell cryopreservation techniques have traditionally relied upon freezing aid chemicals such as dimethyl sulfoxide, or DMSO, which is not approved for use in stem-cell-based therapy products aimed for human use. A new freezing technique developed by Devireddy and Gimble uses the polymer PVP, which humans can digest, as a freezing agent to improve stem cell viability after freezing.

Devireddy and Gimble are also investigating whether inducing stressed states in stem cells can spur these cells to produce natural stress proteins that can help the cells better survive cyropreservation. “It’s like asking whether exercising would improve your survival to a car crash. The stress stimulus for the stem cells is like working out, and the freezing process is like a car crash for these cells,” said Devireddy. “We are essentially trying to toughen up the stem cells before freezing them.”

The aims of the joint research between Devireddy’s and Gimble’s laboratories are to explore the chemical keys that would improve the freezing process in stem cells, and to harness the capability of adult stem cells isolated from human fat tissue to transform into other tissue types, including bone tissue, to create new and improved bone implants. “As bone degenerates with age, bone implantation and regeneration has value to human quality of life,” said Devireddy.

Devireddy and Gimble aim to seed adipose-derived stem cells onto engineered bone-like scaffolds, mechanical structures like the supporting beams of a building, which can help these stems cells become bone cells. Collaborating LSU researcher Daniel Hayes, assistant professor in the LSU Department of Biological and Agricultural Engineering, is helping to provide the bone-like scaffolds for the project.

“A better freezing mechanism for stem cells would allow researchers to maintain a long-term and uncontaminated stock of stem cells while shipping samples to other labs for research or clinical studies without the worry of loss of cell viability and functionality,” said Devireddy. By identifying a freezing process coupled with a natural stress-related protein states that preserve the viability and stemness of stem cells, Devireddy and Gimble hope to develop “off the shelf” products for bone tissue engineering and other stem-cell-based therapies.  “The things we learn from this orthopedic-related study could have value when using stem cells for other problems requiring cosmetic, reconstructive or vascular surgery” added Gimble. 

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