Treating a Damaged Liver: Bone Marrow CD45 Cells are Superior to Mesenchymal Stem Cells


Scarring of the liver, otherwise known as “liver fibrosis” usually results when the liver is constantly assaulted by inflammation. Conventional treatments for liver fibrosis are usually not very effective. Therefore, mesenchymal stem cells (MSCs) is an attractive alternative due to their ability to suppress inflammation. Unfortunately, transplanted MSCs tend to show poor survival in the scarred liver, and they have an additional tendency to stimulate the formation of new scar tissue. These characteristics have bred skepticism among many investigators.

New work by Asok Mukhopadhyay and his colleagues from New Delhi, India has compared bone marrow (BM)-derived cells with MSCs as a treatment for liver fibrosis. They used CCl4 to induce liver fibrosis in laboratory mice. Then they treated liver-damaged mice with either BM-CD45 cells or fat-based MSCs.

Liver tests and tissue samples of both sets of mice clearly showed that the BM-CD45 cells did a much job attenuating liver scarring than did the fat derived MSCs. Interestingly, the anti-scarring capacity of the BM-CD45 cells was compromised by the presence of MSCs.

Why did the BM-CD45 cells do a better job? The bone marrow cells expressed rather high level expressions of matrix metalloproteinases. These enzymes chopped through scar tissue and also suppressed the hepatic stellate cells, which are responsible for making the scar tissue in liver. Apparently, the BM-CD45 cells induced the die off of the stellate cells. MSCs, however, released two growth factors (TGFβ and IGF-1) that are known to activate hepatic stellate cells, and promote the formation of scar tissue. As an added bonus, transplantation of CD45 cells led to functional improvement of the damaged liver, and this functional improvement seems to the result of improved liver repair and regeneration.  Thus transplanted MSCs were pro-scarring while transplanted BM-CD45 cells were pro-regeneration, at least in the liver.

To summarize the results of these experiments, BM-derived CD45 cells appear to be a superior candidate for the treatment of liver fibrosis. The structural and functional improvement of CCl4-damaged livers was substantially better in animals that received transplants of BM-CD45 than those who received fat-derived MSCs.

Umbilical Cord Blood Cells Combined with Growth Factors Improves Traumatic Brain Injury Outcomes


Approximately 2 million Americans experience a traumatic brain injury every year. Most of these are individuals who employed in high-risk jobs such as the military, firefighting, police work and others types of essential but highly dangerous jobs. No matter how small the injury, individuals who have suffered a traumatic brain injury (TBI) can suffer from a whole host of motor, behavioral, intellectual and cognitive disabilities over the short or long-term. Unfortunately, there are few clinical treatments for TBI, and the few we have are rather ineffective.

In order to design better, more effective treatments for TBI, neuroscientists at the Center of Excellence for Aging and Brain Repair, Department of Neurosurgery in the USF Health Morsani College of Medicine, University of South Florida, have used umbilical cord stem cells in combination with growth factors to treat TBIs in mice.

This study investigated the ability of several strategies, both by themselves and in combination with other therapies, to treat rats with a laboratory form of TBI. In particular, the USF team discovered that a combination of human umbilical cord blood cells (hUBCs) and granulocyte colony stimulating factor (G-CSF), a growth factor, was more therapeutic than either administered alone, or each with saline, or saline alone.

“Chronic TBI is typically associated with major secondary molecular injuries, including chronic neuroinflammation, which not only contribute to the death of neuronal cells in the central nervous system, but also impede any natural repair mechanism,” said study lead author Cesar V. Borlongan, PhD, professor of neurosurgery and director of USF’s Center of Excellence for Aging and Brain Repair. “In our study, we used hUBCs and G-CSF alone and in combination. In previous studies, hUBCs have been shown to suppress inflammation, and G-CSF is currently being investigated as a potential therapeutic agent for patients with stroke or Alzheimer’s disease.”

In previous studies, Borlongan and his team showed that G-CSF can mobilize stem cells from bone marrow and induce them to home to and infiltrate injured tissues. While there, the cells promote neural cell self-repair. Cells from human umbilical cord blood also have the ability to suppress inflammation and promote cell growth.

“Our results showed that the combined therapy of hUBCs and G-CSF significantly reduced the TBI-induced loss of neuronal cells in the hippocampus,” said Borlongan. “Therapy with hUBCs and G-CSF alone or in combination produced beneficial results in animals with experimental TBI. G-CSF alone produced only short-lived benefits, while hUBCs alone afforded more robust and stable improvements. However, their combination offered the best motor improvement in the laboratory animals.”

“This outcome may indicate that the stem cells had more widespread biological action than the drug therapy,” said Paul R. Sanberg, distinguished professor at USF and principal investigator of the Department of Defense funded project. “Regardless, their combination had an apparent synergistic effect and resulted in the most effective amelioration of TBI-induced behavioral deficits.”

This particular study examined motor improvements or improvements in movement, but the USF group suggested that future combination therapy research should also include analysis of cognitive improvement in the laboratory animals with TBI.

In short, umbilical cord cell and growth factor treatments tested in animal models could offer hope for millions, including U.S. war veterans with traumatic brain injuries.

Post-script:  On Twitter, Alexey Bersenev made some very helpful observations about this paper.  In this paper, the authors used whole human umbilical cord blood.  They did not attempt to separate any of the different cell types from the cord blood.  Now when such whole blood is used, it is easy to assume that the stem cells in the blood that are doing the regenerative work.  However, as Alexey graciously pointed out, you cannot assume that the stem cells are responsible for the therapeutic effects for at least two main reasons:  1)  the number of stem cells in the cord blood is quite small relative to the other cells; 2) some of the non-stem cells in the blood turn out to have therapeutic effects.  See here and here.  I have seen some of these papers before, but I did not think much of them.  Therefore, until the cell populations in the umbilical cord blood are dissected out and studied, all we can say with any confidence is SOMETHING in the cord blood is conveying a therapeutic effect, but the identity of the therapeutic culprit remains unclear at this time.