Bone Marrow or Umbilical Cord Stem Cells Treat Refractory Lupus-Related Kidney Disease


Autoimmune diseases are those diseases in which the patient’s own immune system attacks his or her own tissues. the treatment of such diseases requires giving patients drugs that suppress the immune system. Such drugs have potent side effects and taking such drugs long-term can also predispose patients to cancers and other types of inimical conditions.

One particular type of autoimmune disease, Systemic Lupus Erythematosis, otherwise known as SLE or just Lupus, results from an immune response against components inside our cells. The recognition of these proteins and other substances by our immune system causes massive cell damage and death. However, lupus is a very individual disease. In some patients, the disease manifests by producing butterfly-like lesions on the face.

Lupus butterfly rash (from http://emedicine.medscape.com/article/332244-overview)
Lupus butterfly rash (from http://emedicine.medscape.com/article/332244-overview)

In others, a severe arthritis in several joints results. In other lupus patients, the liver undergoes progressive degradation and scarring. Still others have severe heart problems, and others have scarring and progressive damage to the kidneys. In other patients a combination of symptoms and organs are affected. Some cases of lupus are sporadic and mild, but others are fulminant and relentless. The particular disease a person shows is completely individual.

In some lupus patients, the kidneys experience lupus nephritis (LN), which is inflammation of the tissues of the kidney. In some patients, drug treatments with corticosteroid drugs like prednisone, or other drugs like hydroxychloroquine (Plaquenil), also can help control lupus. Other drugs include powerful immune suppressants such as cyclophosphamide (Cytoxan), azathioprine (Imuran, Azasan), mycophenolate (Cellcept), leflunomide (Arava) and methotrexate (Trexall), all of which have lists of side effects that include increased risk of infection, liver damage, decreased fertility and an increased risk of cancer. However in a percentage of LN patients, drug treatments simply do not work, and these conditions are known as refractory LN.

A new clinical trial has examined the ability of mesenchymal stem cells from bone marrow or umbilical cord tissue to treat refractory LN. This Chinese study examined 81 patients with active refractory LN. The mesenchymal stem cells (MSCs) used in this study were “allogeneic,” which means that they were taken from someone other than the patient. Such treatments have been shown to successfully treat patients with other types of autoimmune diseases (see Figueroa FE, et al., Biol Res. 2012;45(3):269-77).

In this single-center clinical trial, Fei Gu and Dandan Wang and others from the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China enrolled 81 Chinese patients with active and refractory LN from 2007 to 2010. These patients received by intravenous administration either allogeneic bone marrow- or umbilical cord-derived MSCs at a dose of 1 million cells per kilogram of bodyweight. All 81 patients were then monitored over the course of one year with periodic follow-up visits to evaluate kidney function and to determine if the patients were experiencing any adverse events from the stem cell treatments.

During the year-long follow-up, 77 of the 81 patients survived ( survival rate of 95%) and 49/81 patients (60.5%) achieved remission. Eleven of 49 (22.4 %) patients showed a “renal flare,” which means that their symptoms and kidney inflammation returned by the end of 12 months after having previously experienced complete remission.

Kidney function jumped during this time. The main measure of kidney function is a test called the glomerular filtration rate or GFR. This measures how well the kidney filters materials per unit time. GFR in these patients improved significantly 12 months after the stem cell treatment (mean ± SD, from 58.55 ± 19.16 to 69.51 ± 27.93 mL/min). Two other measures used to determine the severity of lupus in a patient (Systemic Lupus Erythematosus Disease Activity Index or SLEDAI score), and the activity of lupus within the kidney (British Isles Lupus Assessment Group or BILAG scores) also decreased consistently, showing that the severity of the disease decreased and the severity of the disease within the kidney also decreased after the stem cell treatment (BILAG scores – 4.48 ± 2.60 at baseline to 1.09 ± 0.83 at 12 month and the SLEDAI scores – 13.11 ± 4.20 at baseline to 5.48 ± 2.77 at 12 months).

If that is not convincing, get this: the doses of prednisone and immunosuppressive drugs required by these patients were tapered. In other words, patients were able to eventually get off their drugs sometime within this year-long period. Is that cool or what!! No transplantation-related adverse events were observed.

Thus, the authors conclude, “Allogeneic MSCT resulted in renal remission for active LN patients within 12-month visit, confirming its use as a potential therapy for refractory LN.”

Now this treatment is NOT a cure. Several patients still experienced renal flares one year after treatment, and not all the patients experienced remission. Therefore, this is not a treatment for everyone. Identifying which patients will be helped by these treatments might require microarray analyses, but the bottom line is clear – some patients are definitely helped by MSC treatments.

Granted this is a small study and it is not a controlled study – these stem cell-treated patients were not compared to anything else. However it is a very hopeful beginning. There were no adverse side effects and 60% of the patients experienced remission, and that is definitely good news

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Published by

mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).