Abstract: It is estimated that some 500,000 children and adults in the United States manifest one or more of the symptoms of cerebral palsy. And stem cells have shown their potential in cerebral palsy treatment.
If 15-year-old Patrick passes in front of you right now, you can hardly imagine that he was suffering from cerebral palsy when he was a baby.
Patrick was born and looked normal, but he couldn't grasp things with his left hand. When he started crawling, his parents found that only his right leg was moving and his left leg was just dragging. All these changes happened when he was 6 years old. Professor Joanne Kurtzberg of Duke University conducted a groundbreaking study, and the family did not hesitate to let Patrick join in the program. The umbilical cord blood preserved at birth returned to Patrick's body again after being cryopreserved for many years.
Now, this child is as normal as other children. Patrick can exercise, walk, and run with his brothers. His improvement has exceeded the expectations of physical therapy (PT) and occupational therapy (OT).
Cord Blood and Stem Cells
Since the Danish scientist Knudtzon discovered hematopoietic stem cells in umbilical cord blood in 1974, scientists have been concerned about its hematopoietic function. In the 21st century, the role of other stem cells in umbilical cord blood has gradually been emphasized.
Studies have shown that cord blood contains many types of stem cells, including hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), very small embryonic-like stem cells (VSELs). These stem cells are the biological basis for the further application of cord blood in regenerative medicine.
Recent studies have shown that cord blood MSCs can be induced to differentiate into osteoblasts, chondrocytes, adipocytes, nerve cells, liver-like cells, etc. under certain conditions. VSELs have a variety of cell characteristics from HSCs to cardiomyocytes. Umbilical cord blood EPC has an outstanding angiogenesis effect, and at the same time, it shows a good synergistic effect when combined with MSCs.
Cerebral palsy is generally caused by brain damage before or during childbirth, which can lead to lifelong disability. The main symptoms of cerebral palsy are backward motor development, abnormal muscle tone, abnormal posture, and abnormal nerve reflexes. Pre-clinical data indicate that the persistent neuroinflammatory response is the cause of further damage caused by cerebral palsy. Scientists are trying to use stem cells to break the vicious circle of inflammation and damage, such as cord blood MSCs.
It is speculated that the mechanism of action of umbilical cord blood MSC in treating cerebral palsy is as the followings.
After brain tissue is damaged, various chemokines are released to attract MSCs to gather. At the same time, ischemia and hypoxia also lead to increased local permeability, which is conducive to MSCs’ crossing the blood-brain barrier.
·Differentiated and substitution
MSCs differentiate into various types of cells in the local microenvironment, replacing and repairing damaged nerve cells.
·Accelerate nerve regeneration
MSCs can secrete a variety of neurotrophic factors, which may inhibit cell apoptosis, promote angiogenesis, increase blood vessel density, improve cerebral circulation and oxygen supply in the injured area, thereby playing an important role in the process of nerve regeneration and repair.
·Activate neural stem cells
At the same time, these cytokines may promote the proliferation and differentiation of endogenous neural stem cells and migrate to damaged areas.
Most importantly, umbilical cord blood MSCs can play an anti-inflammatory effect by regulating the paracrine and cytotoxic effects of T cells, B cells, dendritic cells, neutrophils, and macrophages, and thus break the vicious circle of inflammation and damage.
“In the US clinical trial database, dozens of clinical trials of umbilical cord blood for the treatment of cerebral palsy can be found. The Duke University study that Patrick participated in was completed in 2017,” said a scientist in the field of stem cell therapy development at Creative Biolabs.
The results of this two-year phase II clinical trial showed that one year after intravenous infusion of autologous cord blood, the motor function of children with cerebral palsy in the high-dose group (a single dose exceeding 2.5×107 cells per kilogram of body weight) was improved, which was even 30% higher than the anticipation.
Currently, Duke University is working on another clinical trial of cord blood/umbilical cord MSCs for the treatment of cerebral palsy, and the results are expected to be announced in 2021.
Globally, perinatal stem cells such as cord blood and umbilical cord are increasingly used in the treatment of cerebral palsy. With the advancement of biotechnology, it’s believed that cerebral palsy can be totally cured effectively.