An Exploration Study of Umbilical Cord Stem Cell Treatment in Lupus
Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus.
Authors: Sun L, Wang D, Liang J, Zhang H, Feng X, Wang H, Hua B, Liu B, Ye S, Hu X, Xu W, Zeng X, Hou Y, Gilkeson GS, Silver RM, Lu L, Shi S. (2010).
Arthritis & Rheumatism, epub ahead of print May 6.
What is the topic?
Stem cells are an early form of a human cell, similar to what is found in a developing embryo, which have the ability to split into new cells and give rise to many different kinds of cells in the body. In fact, stem cells can still be found in the body after a baby is born and throughout life. In animal studies, stem cells taken from the umbilical cord (which connects the mother to the baby during pregnancy) have been found to help treat a variety of diseases, including lupus. However, umbilical cord stem cells have not been given to humans before.
What did the researchers hope to learn?
The researchers hoped to determine whether umbilical cord stem cells could be given safely to people with severe and treatment-resistant lupus, and whether this might help to treat lupus.
Who was studied?
16 patients, mostly women aged 17-55 years who had lupus for an average of 65 months, participated in the study. All of the patients had failed to respond to cyclophosphamide (Cytoxan®) for at least six months or mycophenolate (Cellcept®) for at least three months. The patients were either taking more than 20 mg of prednisone per day, had low platelet counts, or had lupus nephritis (active kidney disease). Otherwise, the patients had to have good function in their bodily organs, have no serious infections, and could not be pregnant or breastfeeding in order to participate in the study.
How was the study conducted?
Stem cells were prepared by the Stem Cell Center of Jiangsu Province in China. They obtained the umbilical cords from healthy mothers in local maternity hospitals who agreed to have these materials taken for this purpose.
Prior to receiving stem cells, most of the lupus patients were given cyclophosphamide infusions for 2 - 4 days.
All 16 patients received the stem cells as an infusion in an amount that was based on their body weight.
After receiving the stem cells, all patients were given 5 - 10 mg prednisone per day and 13 patients were also given 0.6 - 0.8 g cyclophosphamide per day.
All 16 patients successfully completed the protocol and were also seen for follow-up visits at 1, 3, 6, 12, and 18 months for an evaluation of their lupus disease activity and for repeated blood tests.
What blood tests were studied in these patients?
1. Regulatory T cells: There is a special kind of white blood cell called a “T cell,” which controls how the immune system works. Some specialized T cells are called “regulatory T cells” and these are important in making the immune system calm down after inflammation. Blood tests can detect these regulatory T cells by measuring two markers called CD4 and FoxP3.
2. Cytokines: Cytokines are small proteins that circulate in the bloodstream to help regulate inflammation. Two of these small proteins include transforming growth factor beta (TGF-β) and interleukin-4 (IL-4).
3. Complement consumption: When lupus is active, some patients will use up too many of some of their inflammatory proteins called “complement proteins.” This can be looked at with a blood test that measures “complement C3,” which is often low in active lupus and especially in lupus kidney disease (active nephritis).
4. Antibodies: Blood levels of anti-double-stranded DNA antibodies were also measured at each visit, as well as other routine tests.
What did the researchers find?
Disease activity decreased significantly for all 16 lupus patients one month after they received the stem cells and the patients were even better at the 3-month follow-up visit.
One way of looking at kidney disease is to measure how much protein is spilling into the urine. This was significantly reduced in 15 patients at the 3-month follow-up visit. Eight patients showed further decreased protein in their urine at the 6-month follow-up and two patients showed reduced levels of protein in the urine for at least one year.
Six patients who had evidence of kidney damage (as determined by high creatinine levels in the blood) also showed significant improvement at the 3- and 6-month follow-up visits.
Blood levels of complement C3 were significantly increased in five patients at the 3-month follow-up visit and anti-double-stranded DNA antibody levels were significantly decreased in 13 patients at the 3-month follow-up visit.
The percentage of regulatory T cells (as determined by the presence of CD4 and FoxP3) was significantly increased at the 3-month follow-up visit in all 16 patients.
Levels of TGF-β in 13 patients were significantly increased and levels of IL-4 were significantly decreased in 12 patients at the 3-month follow-up visit (which could promote regulatory T Cells and dampen antibody production).
Severe nausea was observed in one of the 16 patients during the initial cyclophosphamide treatment. No other adverse events occurred during or after the stem cell procedures.
What were the limitations of the study?
There was no control group in this study. A control group is a group of patients that receives all of the same treatments except the one under study. To see whether stem cell treatment is effective, you would need to have a group of patients who received Cytoxan and/or steroids without the stem cell treatment and see if those who did get the stem cells did better than the patients receiving Cytoxan did. At this point, it is clear that the patients got better, but it is not clear whether that was due to the stem cells or the other treatments they received. Therefore, further studies with more patients followed for longer periods and compared against those receiving standard treatment will be necessary to determine the long-term safety and effectiveness of umbilical cord stem cells in treating lupus.
What do the results mean for you?
We have been hearing about stem cell treatment for lupus for a long time, but some of the procedures used in the past involved very severe depletion of the immune system, which could be extremely dangerous. This may be a less drastic way to approach the treatment of lupus with stem cells. So far, in this early study, it seems to have been well-tolerated. This paves the way for further studies that might really determine the potential of this treatment, whether it is reasonably safe, and whether it might be effective.