Mesenchymal Stromal Cells, Cellular Therapy, and Lupus

Cellular therapy, such as Mesenchymal Stromal Cells, might succeed where other lupus treatments fail for people with SLE. 

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease. Autoimmune diseases involve body’s natural inflammatory response, which the body uses to fight disease, except in this case it is turned against the body’s own cells.  SLE has the potential to harm and hinder any organ in the body, and so has a huge list of possible symptoms. Every person with SLE is different and symptoms and range from mild to severe.

Lupus is usually treated with medications that suppress the immune system. Although immunosuppressants and corticosteroids can leave people with lupus vulnerable to infections and have nasty side effects, they can also prevent flares and bring lupus symptoms down, sometimes sending the lupus into remission! Medications can be a massive relief for people with lupus, and enable millions of people to live normal, productive lives. However, not everyone with lupus find success with the usual gold-standard medications.

In their case, alternative and cutting-edge therapies such as Mesenchymal Stem Cells (MSCs) may be the answer.

Cellular Therapies for Refractory Lupus

Lupus that doesn’t respond to other treatments is known as “refractory lupus.” Cellular therapies are a new field for lupus with the potential to succeed where immunosuppressives and biologic medications  fail. 

Cellular therapies involve the injection of modified human stem cells in order to treat disease. Often, these cells are taken from the person they will be administered to, grown in a lab, and modified. Once there are enough cells and have the properties they need, they are then injected into the body, ideally close to where they can do the most good. 

Mesenchymal Stromal Cells (MSC) are a particular type of hematopoietic stem cell found throughout the body. Hematopoietic stem cells are the parents of both immune and blood cells, and mesenchymal cells can become connective tissue, replacing organ tissue damaged by SLE. Because they are found in bone marrow, blood, skin, and fat, MSCs are easy to extract from the body and grow in the lab. Bone marrow cells are the most common source of MSCs. After extraction, they are grown in a lab for 1-5 days and then purified so that only MSC cells are present. They can be injected locally or systemically, that is – at the point of symptoms or into the body in general.

Cellular therapies are already being used where other medications fail and stem cell therapy, including MSCs, may be a lifesaver for people with refractory lupus if the clinical trials pan out.

How do Mesenchymal Stem Cells Work?

MSCs can differ based on the tissue they are sourced from, but all MSCs have similar properties. MSCs inhibit the immune system, protect the nervous system, and regenerate tissues throughout the body. 

Inflammation is a process: When muscle or skin tissue is damaged or antibodies react to something they target, inflammatory particles are released that alert the immune system. The immune system then sends over cells appropriate to the damage or pathogen, such as T-cells and B-cells. But that’s not all – The body is also set to a higher level of sensitivity to these pathogens, like an alert level.  It becomes more likely to react to injury, pathogens or – in the case of autoimmune disease – attack its own cells. Immunosuppressives prevent the cycle from happening in the first place, a sort of blanket lockdown on the whole body. MSCs, however, act on the source – they come in at the earliest stages of this cycle.

MSCs in the body home in on damaged cells by following chemical signals left by the damaged tissues – they essentially sniff it out. MSCs then travel in between cells, breaking down and then reforming the connective membrane between them (also known as the basement membrane,) to where it is needed. 

Also, some of the cells that originate from MSCs also modulate immune responses, which are out of balance in lupus. When exposed to cytokines, the alarm bells of the immune system, these cells produce nitrous oxide (NO) which inhibits T and B cells, the cells that are involved with lupus.

Do MSCs Work for Lupus?

One of the things these stem cell therapies have in their favor is that nothing foreign is introduced into the body. The cells are taken from a patient’s own body! Literally, the patient heals themselves.

However, as a new field, the efficacy and mechanisms of action of these therapies are still being investigated, as well as their limitations and side effects.  However, things look promising: MSCs have been used for Crohn’s disease, which is a chronic inflammatory disorder in the gastrointestinal tract. They may also have use in treating heart disease and even cancer. It’s not yet clear whether MSC treatments heal the organs, regulate the immune system, or both, but these therapies are showing a lot of promise in clinical trials, reducing symptoms and improving health. 

The MSCs of people with lupus are actually slightly different from normal. They die off faster and are less effective at suppressing inflammation. The reason for this is unclear, but they still effect inflammation and may still be a boon for lupus warriors. Other experiments show a boosting of anti-inflammatory effects of immunosuppressive drugs and a reduction in side effects. Even when they are unable to survive the injection process, the MSCs still decrease antibody production and increase the presence of regulatory T-cells, which police the immune response and are responsible for making the immune system work properly. 

According to reviews, MSC therapy shows a 5 year survival rate of 84% for lupus. 34% of patients with lupus enter clinical remission and systemic lupus symptoms seem to be reduced as measured by SLEDAI, blood tests, and proteinuria. 

SLEDAI is an accurate and reliable measurement of lupus-related activity that includes laboratory tests. Though it doesn’t measure severity and does not, itself, describe whether the patient improved or declined, it is an objective, science-based way to determine the state of lupus in a person’s body at that time.

Currently, MSC therapy is being tested in a phase-2 Clinical Trial, triple blind controlled assessment of MSC versus Placebo in SLE patients receiving Standard of Care Therapy for Severe Renal Disease. No adverse effects have been noted in clinical trials, and there was no change in blood or organ function. So – at present – MSCs are safe to use for SLE. People taking MSCs had reduced symptoms throughout the body, including the kidneys, skin, and blood, and even entered remission.

Overall, several review papers have concluded:

“Although the processing of MSCs is a costly process with complicated steps for safety and quality control (208), this therapy still has great potential, particularly for patients with refractory diseases.”