Search UMDNJContact GSBS

Featured Faculty Member

Featured Graduate Student


Hot Topics

Repair of chicken embryonic spinal cord by adult human hematopoietic stem cells

(Sigurjonsson OE et al, Proc Natl Acad Sci USA 2005;102:5227-32)
Summary by Dacia Foster and Raghav Murthy

LAY SUMMARY

A stem cell is an uncommitted cell that has the ability to give rise to different types of cells. The Hematopoetic Stem Cell (HSC) is currently one of the most studied stem cells.  They reside in the adult bone marrow, which is the thick section inside the bones, where they generate blood and replenish the immune system throughout life. While some studies have shown the capability of HSCs to form cells other than blood and immune cells, others have challenged this type of findings. Previous studied reported that only a small percentage (1-2%) of HSCs can form neuron-like cells (brain cells) when the HSCs are delivered in the right conditions.

HSC in human (hHSC) have marker that identify them, such as CD34.  A marker is an ID tag for a cell and therefore allows its identification. The scientists obtained CD34-expressing hHSCs and then injected them into chicken embryos with cut/damaged spinal cords.  A chicken embryo is at the early stage of development (before hatching). Injecting hHSCs instead of chicken HSCs is an advantage since this allows tracking of the human cells within the chicken by seeking for human markers. In this study, the authors examine the cells for human nuclear antigen.

Approximately 4-9 days after injection of hHSCs, the scientists noticed that the stem cells were developing into neurons mainly at the site where the spinal cord was damaged.  In order to prove that the newly form cells were neurons, studies were done to determine that the cells have neuron markers. These cells not only possessed these markers but their shapes were consistent with neurons. The generation of neurons was specific to damaged tissues since similar injection into normal/undamaged spinal cords showed no evidence of newly formed neurons. Therefore, when the spinal cord is damaged, there must be a change in the environment at or near the damaged site that causes the HSCs to form neurons to repair the damaged spinal cord. These results have significant clinical implications for future methods to use a patient’s own HSCs to repair neural related injury. However, as shown in this article, it is imperative that scientists should understand the chemicals released in the area around the site of injury to allow the HSCs to form neurons.

SCIENTIFIC
Hematopoetic stem cells (HSC) are the source of blood and immune cells. Throughout the adult life span, the HSCs continuously replenish the blood and immune systems while protecting themselves through self-renewal. Research studies have shown HSCs have been show to transdifferentiate into cells of ectodermal origin, specifically neurons.  In previous experiments, only 1-2% of HSCs injected intravenously into normal rodent host embryos differentiated into neurons. This article reports on an improved efficiency of HSCs to generate neurons. The generation of neurons is partly facilitated if the HSCs are placed in the proper microenvironment.

Lesions in the developing brain and spinal cord of chicken embryos normally repair themselves by the process of regulative regeneration.  In this case, neural stem cells replace the lost neurons. The authors hypothesized that the change in the microenvironment during regulative regeneration may induce HSCs to transdifferentiate into neurons. Also, the embryonic microenvironment has little or no immune response, thus the host chicken embryo would be less likely to reject the injected HSCs.  To this end, the investigators implanted CD34+ HSCs from adult bone marrow donors, into spinal cord lesions of chicken embryos. After 4-9 days, immunohistochemistry, electrophysiology, and retrograde axonal tracing techniques were used to confirm and analyze the generation of neurons from the hHSCs. 

The results showed that human HSCs were integrated in ~60% of the chicken embryos.  The neurons formed from the hHSC were verified by staining for the neural markers, MAP2 and NeuN. Discrimination between human and chicken HSCs was done by immunohistochemistry for human nuclear antigen (hNA).  Using retrograde axonal tracing, the researchers labeled both spinal interneurons and motor neurons with fluorescent dextran amines to assess the cell structure. The retrograde labeling showed the human neuronal cell morphologies to be indistinguishable from the host cell neurons. The human HSC-derived neurons demonstrated the presynaptic markers GABA and synaptotagmin. Patch clamp recordings confirmed that the human HSC-derived neurons were functional. 

When the human HSC were placed ex vivo, they did not generate neurons. Thus, the authors concluded that HSC have the ability to create neurons when placed in the proper microenvironment.  This paper supports the possibility of HSCs being able to treatment and/or regenerate neural injuries, such as a spinal cord injury. The studies form the basis for future research to identify the molecular signals that allow HSCs to generate neurons.
THE FOLLOWING CARTOON SUMMARIZES THE ABOVE DISCUSSION

Homeostasis