What is Rhematoid Arthritis (RA)?

Rheumatoid Arthritis (RA) is an autoimmune disease in which the patient’s immune system generates
cellular and antibody responses to various components of the joint such as type I collagen. As a result
of this immune response, not only does joint destruction occur, but also other complications such as
pulmonary fibrosis, renal damage, and even heart damage.
RA causes painful swelling to joints as well as destruction of the cartilage and a weakening of the
surrounding muscles, ligaments and tendons occurs, all of which can make it very difficult to move.
Some patients with RA experience persistent joint damage and pain, while others alternate between
flare-ups and periods of remission. This condition may also lead to microvascular dysfunction and
severe cardiovascular risk

A hallmark of RA joint pathology is chronic inflammation of the synovium (synovitis), which causes
cartilage and bone erosion via interplay between infiltrating inflammatory/immune cells and the
resident fibroblast-like synoviocytes (FLSs).

Current treatment modalities for RA & their Limitations:

Newly diagnosed rheumatoid arthritis is currently treated with immune suppressive agents such as
steroids, methothrexate, cyclosporine, gold, and more recently infliximab (Remicade).
Despite inducing temporary improvement, these approaches possess long-term adverse effects due to
non-specific inhibition of immune responses. When disease-modifying anti-rheumatic drugs
(DMARDs) like methotrexate are not effective, biologics like abatacept (Orencia), adalimumab
(Humira) or etanercept (Enbrel) may be recommended.
None of these treatments address the issue of damage that has already occurred to the joints or extraarticular tissues and this is where Stem cell therapy comes into picture.

Which kinds of stem cells are used to treat rheumatoid arthritis and how are they obtained?

Adult stem cells called allogeneic mesenchymal stem cells (MSCs) are used to treat rheumatoid
arthritis. These cells are harvested from human umbilical cords donated after normal, healthy births. All
mothers who donate umbilical cords undergo infectious disease testing and medical history screening
before donation is accepted.

How are mesenchymal stem cells administered for rheumatoid arthritis treatment?

They are typically given intravenously (IV) over the course of a few days.

Rheumatoid Arthritis Stem Cell Treatment Protocol

A typical 4-day rheumatoid arthritis treatment protocol involves,
• Medical evaluation and blood testing
• 6 IV injections of allogeneic umbilical cord mesenchymal stem cells

How stem cells offer benefit to patients with RA?

Mesenchymal stem/stromal cells (MSCs) have tremendous flexibility to make a variety of different cell
types, including bone, fat, muscle, cartilage, bone marrow and tendon. MSCs offer lasting benefit or at
least some relief to patients with RA as well as address microvascular complications by carrying out the
important jobs of:
• Improving blood flow
• Reducing inflammation
• Repairing and replacing damaged tissue
• Halting destructive immune system response

MSCs localise to inflamed tissue and start producing anti-inflammatory agents. These mediators act
locally and do not suppress the immune response of the patient’s whole body. Additionally, MSCs
induce the production of T regulatory cells, a type of immune cell whose function is to protect the body against immunological self-attack.

MSCs produced a significant decrease in pro-inflammatory cytokines IL-6 and TNF-α, both of which
are temporarily targeted by many current RA treatments – without the long-term side effects.
Transplanted MSCs do not lead to extensive graft rejection even when the donor and recipient are

Thus, the mechanisms through which MSCs can influence joint disease processes are diverse and
include immunosuppressive and anti-inflammatory effects, trophic/paracrine effects and direct
contribution to tissue repair.



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