According to the official website of the Department of Health and Ageing of the Australian Government, the Australian government will invest 55.24 million US dollars in the research and development of stem cell therapy and infrastructure construction recently. The main purpose is to alleviate difficult-to-treat diseases such as osteoarthritis and rheumatoid arthritis through the research and development of new treatment methods.

Osteoarthritis and rheumatoid arthritis have always been the most difficult problems among bone and joint diseases. Patients may suffer from joint pain and deformity, which seriously affects their daily life. In recent years, with the emergence of regenerative therapies such as stem cells, new hope has been brought to such patients!

A Brief Introduction to Osteoarthritis and Rheumatoid arthritis

Osteoarthritis

Osteoarthritis (OA), also known as "senile arthritis" or "degenerative arthritis", is a chronic degenerative joint disease characterized by secondary bone hyperplasia and degenerative changes in articular cartilage. It can occur in multiple joints of the body, with the knee joint being the most common.

Knee osteoarthritis (KOA) is one of the most common types of osteoarthritis (OA), mainly characterized by damage to cartilage and subchondral bone. Patients may present with manifestations such as joint pain, stiffness, limited movement, and joint deformity. Intra-articular injection of mesenchymal stem cells (MSCS) with immunomodulatory properties provides a non-invasive treatment option for patients with osteoarthritis, which helps relieve pain and promote cartilage regeneration.

Rheumatoid arthritis

▲ Image source: "Shutterstock"

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Common symptoms include joint pain, joint swelling, joint stiffness, etc. It is often accompanied by joint dysfunction, and in severe cases, it can even lead to progressive disability.

At present, there is no very good treatment method. In clinical practice, symptomatic treatment mainly relies on corticosteroids, antirheumatic drugs, etc. However, long-term use of antirheumatic drugs may lead to drug resistance in patients, thereby resulting in poor treatment effects.

Mesenchymal stem cells can differentiate into various tissues such as cartilage, muscle, tendon, ligament and bone, and can regulate immune responses and promote regeneration. They have great application potential in the treatment of rheumatoid arthritis and can help improve the severity of rheumatoid arthritis.

Important research on stem cell treatment of osteoarthritis and rheumatoid arthritis

Stem cell therapy for osteoarthritis alleviates pain and inflammation, and increases the thickness of articular cartilage

▲ Screenshot from "BMC"

"Stem Cell Res Ther" reports a Phase II clinical study on "the application of allogeneic adipose-derived mesenchymal stem cells in the treatment of knee osteoarthritis". A total of 40 patients with knee osteoarthritis (KOA) were enrolled in this study and divided into two groups: the stem cell group [20 patients, given allogeneic adipose-derived mesenchymal stem cells (AD-MSC)] and the placebo group (20 patients, given normal saline). After one year of follow-up after treatment, the results showed that:

1. Inflammation is relieved

In the stem cell group (i.e., patients treated with AD-MSCs), the levels of hyaluronic acid and cartilage oligomeric matrix protein in the serum were significantly decreased (P<0.05). The levels of serum inflammatory markers decreased sharply after 3 months (P<0.001). The expressions of CD3, CD4 and CD8 showed a downward trend during the 6-month follow-up (P<0.05), (P<0.001), and (P<0.001), respectively.

2. Symptom relief

①WOMAC Knee Joint Function Score Scale: Compared with the placebo group, the total WOMAC score of patients in the stem cell group decreased significantly. After 6 months of stem cell treatment, the average score dropped by more than 70% (see the figure below for details).

▲ Image source: "Stem Cell Res Ther"

② VAS score for knee pain: Compared with the placebo group, the VAS score of patients in the stem cell group showed a significant downward trend (see the figure below for details), indicating that the pain symptoms of the patients were significantly alleviated.

▲ Image source: "Stem Cell Res Ther"

③SF-36 Quality of Life Scale: By comparing the score results of the SF-36 scale, the health status of patients in the AD-MSCs group was significantly improved (see the figure below for details).

▲ Image source: "Stem Cell Res Ther"

Note: PF- Physical Function RP- Body Role BP- Body pain GH- General Health VT- Vitality SF- Social Function RE- Emotional Role MH- Mental Health.

3. Thickness of articular cartilage

MRI showed that the thickness of the articular cartilage of the tibia and femur in the AD-MSCs group slightly increased, especially the changes in the posterior and anterior tibia regions were significant (P<0.01 and P<0.05). Among them, the changes of one patient before and after the injection of AD-MSCs are as follows:

① The thickness of the anterior lateral tibia (TLA) : 2mm respectively (before stem cell injection) vs 2.08mm (one year after injection);

② The thickness of the central lateral tibia (TLC) : 1.76 mm (before stem cell injection) vs 1.79 mm (one year after injection), respectively;

③ The thickness of the posterior lateral tibia (TLP) : 1.64 mm (before stem cell injection) vs 1.72 mm (one year after injection), respectively;

④ Anterior medial tibia (TMA) thickness: 2.24 mm (before stem cell injection) vs 2.26 mm (one year after injection), respectively;

⑤ Central thickness of the medial tibia (TMC) : 2.51 mm (before stem cell injection) vs 2.65 mm (one year after injection), respectively;

⑥ Posterior medial tibia (TMP) thickness: 1.85 mm (before stem cell injection) vs 1.84 mm (one year after injection), respectively.

MRI comparison images of the tibial condylar cartilage of this patient before the injection of AD-MSCs and one year after the injection

▲ Image source: "Stem Cell Res Ther"

The above results indicate that intra-articular injection of AD-MSCs for the treatment of osteoarthritis is safe and feasible. Both MRI results and clinical examinations show that the regeneration of articular cartilage in the treatment group is obvious and the improvement degree is significant.

After stem cell therapy for rheumatoid arthritis, joint swelling and tenderness improved

▲ Screenshot from "BMC"

The Journal Stem Cell Research & Therapy recently reported an I/IIa clinical study (NCT03691909) on the treatment of rheumatoid arthritis (RA) using "autologous adipose-derived mesenchymal stem cells (AD MSCs)". A total of 15 rheumatoid arthritis patients aged between 18 and 65 years were enrolled in this study. After receiving autologous adipose-derived mesenchymal stem cell treatment, the results showed:

1. Count of swollen joints

Compared with the baseline before treatment, the count of swollen joints (measured based on the ACR 66/68 joint assessment) was significantly reduced in each follow-up. At the end of the 52nd week of follow-up, the score of the swollen joint improved significantly. The median dropped sharply from 12.0 (IQR 8.0-19.0 before stem cell therapy) to 1 (IQR 0.0-3.0 at 52 weeks of stem cell therapy), as detailed in the following figure.

▲ Image source: "Stem Cell Research & Therapy"

2. Score of tender joints

Compared with the baseline before treatment, the tender joint score decreased significantly in each follow-up. At the end of the 52nd week of follow-up, the tenderness joint score (measured based on the ACR 66/68 joint assessment) improved significantly. The median dropped sharply from 20.0 (IQR 11.0-36.0 before stem cell therapy) to 1.0 (IQR 0.0-4.0 at 52 weeks of stem cell therapy), as detailed in the following figure.

▲ Image source: "Stem Cell Research & Therapy"

The above results indicate that a single intravenous injection of autologous adipose-derived mesenchymal stem cells can safely and effectively improve joint function in patients with active rheumatoid arthritis.

Editor's Note

Osteoarthritis and rheumatoid arthritis have long been major problems in the field of bone and joint diseases. Moreover, the current clinical treatment methods are limited, mainly focusing on symptomatic treatment. This is also one of the important opportunities for Australia to invest heavily in the research and development of new therapies this time.

In recent years, with the continuous development of regenerative medicine, stem cell therapy, which has functions such as anti-inflammation, immune regulation, and self-repair, has gradually shown great application potential in the treatment of osteoarthritis and rheumatoid arthritis, helping to improve clinical symptoms, delay or prevent the progression of diseases, and enhance the quality of life of patients! The editor also hopes that with the continuous deepening of research and development in various countries, more new therapies will be introduced in the future, benefiting more patients with bone and joint diseases!