Long-Term Safety of Umbilical Cord MSCs for Lupus

Mesenchymal stem cells (MSCs) are multipotent cells that can be derived from different sources, including adult and fetal tissues. They can be derived from bone marrow, fatty tissue, cord blood, umbilical cord, placenta, amniotic fluid, synovium, and dental pulp. 

There are currently over 300 clinical trials evaluating MSCs therapeutic utility in a variety of diseases including osteoarthritis, wound healing, cardiovascular disease, and also different autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, and multiple sclerosis. 

New research study on the long-term safety of Umbilical cord MSCs 

A research study published in the journal Clinical and Experimental Medicine by Dandan Wang and colleagues aimed to evaluate the long-term safety of allogeneic umbilical cord mesenchymal stem cells (UC-MSCs) transplantation for patients with refractory systemic lupus erythematosus (SLE). 

The study included 9 SLE patients, who were refractory to steroid and immunosuppressive drugs treatment and underwent MSCs transplantation in 2009. They had 1 million allogenic UC-MSCs per kilogram of body weight infused intravenously at days 0 and 7. 

The research team excluded patients from the study if they had the following conditions:

• Infection: Including pneumonia, pulmonary tuberculosis, hepatitis, skin infections, central nervous system infection.
• Heart failure. New York Heart Association functional classification III or IV. 
• Hepatic failure, respiratory failure, or renal failure.
• Pregnant or lactating woman. 

UC MSCs were prepared by the Stem Cell Center of Jiangsu Province, which is the National Stem Cell Institute in China and a member of the International Society for Cellular Therapy (ISCT). The Stem Cell Center was also certified by the American Association of Blood Banks (AABB).

All the patients were allowed to report any discomfort at any time to the doctors after MSCT. The possible adverse events, including immediately after MSCs infusions, as well as the long-term safety profiles, were evaluated by taking routine blood tests, liver function, electrocardiogram, chest radiography, and serum levels of tumor markers, including alpha fetal protein (AFP), cancer embryo antigen (CEA), carbohydrate antigen 155 (CA155), and CA199, were determined before and 1, 2, 4 and 6 years after MSCT.

The only adverse events reported were mild dizziness and warm sensation 5 minutes after the infusion, and symptoms disappeared quickly. 

There was no change in peripheral white blood cell count, red blood cell count, and platelet number. Also, liver functional analysis showed that serum alanine aminotransferase, total and direct bilirubin, and glutamic-oxalacetic transaminase remained in normal ranges after the therapy. No newly onset abnormality was detected on EKG or chest radiography, and no rises of serum tumor markers were observed. 

Conclusions

According to the researchers, their present study has the limitation of having a small number of patients. But the results of this and other studies using UC-MSCs have shown no major adverse effects, which demonstrates that the treatment is safe and no tumor-related adverse events related to the therapy in a 6-year observation. There is of course a need for larger studies with a large number of patients treated with MSCs and a longer follow-up time is needed before widespread clinical application of MSCs in SLE therapy. 

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Source:

Wang, D., Niu, L., Feng, X., Yuan, X., Zhao, S., Zhang, H., … Sun, L. (2016). Long-term safety of umbilical cord mesenchymal stem cells transplantation for systemic lupus erythematosus: a 6-year follow-up study. Clinical and Experimental Medicine, 17(3), 333–340. doi:10.1007/s10238-016-0427-0

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https://www.medschool.umaryland.edu/research/areas-of-excellence/excellence-in-stem-cell-research/