Mesenchymal Stem Cells in the treatment of Systemic Lupus …

by Neil Riordan, P.A., Ph.D.

Neil Riordan, P.A., Ph.D.

There are four different types of lupus erythematosus, a group of diseases commonly referred to simply as "lupus." Systemic lupus erythematosus(SLE) is the most common and serious form.

Professor Lingyun Sun and his colleagues have written five key articles about the treatment of Systemic Lupus Erythematosus (Lupus) with mesenchymal stem cells. I had the pleasure of meeting Professor Sun on a trip to China in 2010. Dr. Sun is at Nanjing University Medical School, in Nanjing, China.

The first of the series1, published in 2009, firstly described benefits of mesenchymal stem cells (MSCs) in a mouse Lupus model. From the positive outcomes they saw in that model, they then went to humans and treated a series of 4 people who were not responding to treatment with cyclophosphamide and steroids for more than six months. Both the mice and humans were treated with donor bone marrow mesenchymal cells that were grown in the laboratory. The lupus patients received a single intravenous (IV) infusion of 1 million cells per kilogram of body weight. For an average sized person the dose would have been 70 million cells.

The patients were tapered off of their cyclophosphamide during the six months following the treatment and remained on a relatively low dose of prednisilone (10 mg per day) for six more months. The net result was that the patients' kidney function, survival, and disease remission improved in the MSC treated patients.

Also of note from this study was that the Lupus patients' own bone marrow MSCs were cultured and they were found to be impaired compared to matched controls. The particular impairment was in the cells' capacity to form bone. They describe this impairment as "an osteoblastic niche deficiency." This deficiency comes along with impaired ability to produce T-regulatory cells key cells for keeping the immune system in check cells that are often decreased in number in patients with autoimmune diseases.

The second article2 in 2010 followed 15 Lupus patients who were treated with again bone marrow MSCs that were cultured in the laboratory. To be included in the study patients had to have severe SLE. To qualify as severe they needed to have a Systemic lupus erythematosus disease activity index (SLEDAI) score >8, refractory low blood platelets, or severe lupus-related kidney disease (lupus nephritis). As with the first publication, patients received a single intravenous infusion of 1 million mesenchymal stem cells per kilogram of body weight. The net result of the study: There were no serious side effects; SLEDAI scores significantly improved at 1, 3, 12, and 24 months; protein in the urine (secondary to kidney disease) significantly improved at 1, 3, 12, and 24 months; and the percentage of the immune-regulating T-regulatory cells significantly increased at 1 week, 3 months and 6 months after treatment.

In the next article3, Sun used donor umbilical cord-derived mesenchymal stem cells instead of bone marrow-derived. In our laboratory experience umbilical cord MSCs can undergo approximately twice the number of "doublings" as their adult-derived bone marrow counterparts. Since the doublings are logarithmic, the actual number of cells that can be grown from a single umbilical MSC is more than 99 percent more than from adult bone marrow. Simply put, umbilical cord MSCs are more potent than MSCs taken from an adult. The patients in this study were refractory to standard treatment and had life-threatening visceral involvement. The take home from this study was: "Significant reduction in disease activity was achieved in all patients, and there has been no recurrence to date and no treatment-related deaths." As with the previous bone marrow MSCs study there was significant improvement in the SLEDAI scores and kidney function, and a significant increase in the number of T-regulatory cells.

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