Rheumatoid Arthritis is a long-term (chronic) inflammatory condition that, over time, can damage not just your joints but also other body systems—nerves, blood vessels, heart, eyes, lungs, and skin. 

As an autoimmune disorder, RA develops when your immune system (the body's natural defenses) attacks body tissues, especially in your joints. Over time, the joint's lining is destroyed, causing swelling, stiffness, pain, and eventually bone damage and joint deformity. 

Severe cases of RA are a major cause of physical disabilities and can even cause psychiatric symptoms.

Nowadays, it's still unclear what causes Rheumatoid Arthritis, but clinical evidence suggests that there might be a genetic link. 

However, your genes don't cause RA. However, they might make someone prone or more likely to develop RA as a reaction to other factors, such as infections or environmental triggers.

Despite the uncertainty about what causes RA, some factors may increase the risk of developing the disease:

• Family: Having a family member with rheumatoid arthritis increases the RA risk.

• Sex: The probability of developing RA is higher in women than men.

• Age: RA is more frequent in middle-aged people, but it can develop at any age.

• Smoking: Smoking is associated with a higher risk of developing RA. Smoking can raise the risk of severe RA if you have a family history or genetic predisposition.

• Overweight: Excess weight has been associated with a higher risk of developing RA.

Rheumatoid Arthritis develops differently for each person. Some have long periods with no symptoms or just a few or milder symptoms, while others experience flares (when symptoms intensify considerably) for months at a time. However, it's important to note that most people progressively develop severe episodes in the long term.

• Your Joints: RA is a disorder that almost always affects your joints, typically starting in your hands, but other joints are also affected:

  • Elbows, wrists, finger joints, knuckles, and ankles

  • RA can also occur in your toes, hips, jaw, knees, neck, and shoulders.

Rheumatoid Arthritis’s first signs may show in a few weeks or months, and later come the typical symptoms:

• Pain: Your joints hurt when moving or not.

• Swelling: Fluid accumulates in your joints, causing puffiness.

• Tenderness: Your joint hurts to the touch.

• Stiffness: Your joints feel stiff to move, especially in the morning; the stiffness can last more than an hour.

• Redness and warmth: RA inflammation may cause the joints to be warmer and change color.

• Your Body: Rheumatoid Arthritis symptoms can affect more than your joints. RA can cause fatigue, muscle pain, low appetite, overall discomfort, bad feeling, and even depression.
  

• Skin: Bumps under the skin can appear in some people with rheumatoid arthritis. Those bumps are called rheumatoid nodules, and they can be painful sometimes. The nodules usually show on your elbows. However, they can also appear on the forearms, back of the head, tendons, and base of the spine.
  

• Heart and Lungs: Rheumatoid Arthritis complications can occur in your organs, bones, and blood vessels. RA inflammation can affect the lining around your lungs and even damage them, causing chest pain and shortness of breath. The disease progression might cause stiffening of your lung tissues, making breathing very hard.

A similar inflammatory process can occur around your heart or in its muscle, increasing your risk of heart failure and stroke.

• Eyes: Common eye complications include cataracts, dry eye syndrome, and even inflammation in the white of your eyes (scleritis).

• Other Parts of your Body: Rheumatoid Arthritis's long-term effects and the chemicals in medications used to treat it can harm other parts of your body, such as bones, immune system, muscles, nerves, blood vessels, liver, and kidneys.

The American College of Rheumatology has developed recommendations for Rheumatoid Arthritis (RA) treatment to delay or prevent the progression of the disease and reduce the loss of function or minimize joint damage. 

The treatment options may involve biological agents and other substances, such as anti-inflammatory drugs, non-steroidal anti-inflammatory drugs, immune-modulators, and, ultimately, surgery. All those are standard treatments for rheumatoid arthritis. They may have limited or even a temporary effect on pain relief and disease progression, but they cannot repair damaged tissues.

According to the clinical literature, Exosomes combined with MSCs help in autoimmune diseases by regulating the inflammatory cytokines, microenvironment, and immune cells. These processes have a potent relation with both adaptive and innate immune cells. In these cells, macrophages, Treg cells, Th17, immunoregulatory miRNAs, and CD4+Th1 are the most crucial ones. 

Exosomes-combined-MSCs help in the regulation of T-Cell subsets in cases of autoimmune diseases. Moreover, the MSCs-Exosomes also aid in reducing the levels and concentration of pro-inflammatory Th17 and TH1 cytokines such as IL-17AF, IL-12p70, and IL-6. However, the same MSCs-Exosomes help in increasing the concentration of anti-inflammatory Treg. 

Therefore, MSCs-Exosomes increase the concentration of Treg cells and the related products without changing the concentration index of the lymphocytes to maintain immunoregulation in the body. Similar effects of these cells are seen in the cases of RA (rheumatoid arthritis) and GVHD (graft-versus-host disease). MSCs-Exosomes help improve the GVHD by suppressing the differentiation of populations of the naïve T-cells. Macrophages constitute a crucial and major portion of the innate immunity of the human body, which can be regulated through the administration of MSCs-Exosomes. According to the different microenvironments, Mo (naïve macrophages) can be polarized into anti-inflammatory (M2) or pro-inflammatory (M1) to play different roles in different conditions. Along with the autoimmune conditions, this combination therapy can also help facilitate metabolic hemostasis to attenuate obesity and adipose inflammation. Moreover, MSCs-Exosomes can also promote the M1-M2 macrophage conversion to reduce the pro-inflammatory factors or effects of the macrophage M1.

Stem Cell Therapy (SCT) is the most innovative and advanced treatment option for Rheumatoid Arthritis. 

SCT's main objective is to provide patients with a satisfactory treatment that stimulates their immunity and promotes tissue regeneration in affected areas. It helps improve the associated symptoms of RA without the adverse effects and risks of the other treatment options. 

SCT is a highly effective and viable option for patients when their current intervention or other treatments do not improve symptoms.