Neonatal Stem Cells for Research and Clinical Applications

I recently attended a lecture presented by Dr. Suzanne Pontow, Co-Director of the California Umbilical Cord Blood Collection Program at the UC Davis Health System and a Stem Cell Research Program Supervisor at the Institute for Regenerative Cures. The lecture titled “Neonatal Stem Cells: A Window to Perinatal Health and Resource for Regenerative Medicine” discussed both research and clinical applications for neonatal stem cells and the California Umbilical Cord Blood Public Bank set for launch in Mid-2012. I will break the talk into a two-blog series; Part I will cover the research and clinical use of the neonatal cells and Part II will cover the new California Umbilical Cord Blood Public Bank.

The University of California, Davis Institute for Regenerative Cures is a $62 million dollar institute supported by the California Institute for Regenerative Medicine*. The philosophy behind the UC Davis Institute is to bring together physicians, research scientists, biomedical engineers and other experts to work in disease teams all with a focus on moving research into clinical trials. There are 14 disease teams that address every major area of the human body and the Institute has planned or initiated clinical trials in retinal occlusion, heart attack, peripheral vascular disease, bone repair and Huntington’s disease. The Institute is also home to one of the largest GMP (Good Manufacturing Practice) facilities for stem cells in the nation. It has 7,000 square feet of space with a suite of six specially designed rooms created to safely process cellular and gene therapies for clinical trials.

A major research tool for the Institute is the use of neonatal stem cells both in research and clinical applications. The neonatal stem cells are collected from placental tissues and cord blood. The stem cells are made up of mesenchymal and hematopoietic cells, which are multipotent cells. Multipotent cells can differentiate into many types of cells, but not all. For instance hematopoietic stem cells can differentiate into several types of blood cells and mesenchymal cells can differentiate into different bone cells, cartilage cells or fat cells, but they are limited to differentiation into these areas. However, both hematopoietic and mesenchymal cells can be induced into a pluripotent state from which they can become any type of cell in the human body.

Researchers at the Institute study neonatal cells in a number of ways. One way researchers use these cells is to compare the neonatal cells of a newborn with any health problems they may have had at birth to see if there is a link on a cellular level. They are also studying the environment of these cells in the placenta to find better ways to culture stem cells. Perhaps the most revealing studies done on these cells are when researchers create “disease in a dish” scenarios. Dr. Pontow described one example where researchers worked with a group of at risk newborns. At risk newborns are babies that either have a genetic disease or have a sibling with a genetic disease and are at risk of developing that disease in the future. Researchers isolated hematopoietic stem cells from the cord blood of newborns at risk for Huntington’s disease. The cells were cultured, induced into a pluripotent state and were differentiated into neurons. By studying these neurons they could see if the neurons were developing normally and they could examine how the neurons responded to various drugs as a way to look for cures or to slow progression of the disease. This “disease in a dish” model is applicable across a wide range of disease types and allows researchers to conduct extensive research about a disease without invasive patient procedures.

In clinical application, researchers at the Institute use neonatal cells for tissue engineering and to improve or create new treatments for genetic diseases and traumatic injuries. One study was described in which they used a mouse model to find a treatment for peripheral artery disease. The neonatal cells used for this study were mesenchymal cells derived from Wharton’s Jelly. Wharton’s Jelly is a tough, gelatinous substance that protects and insulates umbilical blood vessels. Cells are extracted by cutting the Wharton’s jelly into pieces and letting the cells come out; cells must be passaged 3-4 times to get rid of extraneous cells. As soon as the cells were cultured and ready for transplant, researchers removed a portion of the mouse’s femoral artery. In the control group, mice were injected with buffer only. In the experimental group, mice received the mesenchymal cells derived from Wharton’s Jelly within 48 hours of the surgery. After 21 days, the control group showed some blood flow was restored, but none down to the foot. In the experimental group, the mice had full blood flow restored all the way to the foot after 21 days. This study is of particular importance to diabetics, who are at high risk of peripheral artery disease and often have difficulty getting blood flow to the feet, sometimes resulting in necessary amputation.

Neonatal cell studies are of great importance when it comes to finding treatments for disease. These cells are readily available, easy to harvest and are “youthful”, which according to Dr. Pontow means that they “last longer in culture and go through more successful divisions than adult derived stem cells.” These advantages make neonatal cells an attractive research and therapeutic tool and with the creation of The California Umbilical Cord Blood Collection Program, there should be more of these cells available for both applications.

* The California Institute for Regenerative Medicine (CIRM) was established after California voters approved Proposition 71 in 2004. The Proposition allocated $3 billion in funding for Stem Cell Research in California.

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