Osteoarthritis affects an estimated 250 million people worldwide and is increasingly becoming younger. Although there are a variety of treatments (such as medications, lifestyle improvements, physical therapy, etc.) to reduce the tissue damage of osteoarthritis, it is mainly to improve the symptoms, and it is difficult to prevent the disease from continuing to progress. Once the disease is terminal, few other effective treatments are available until joint replacement is needed.

However, with the development of regenerative medicine in recent years, in addition to the umbilical cord mesenchymal stem cells and autologous fat stem cells that we are familiar with, another "magical" stem cell has gradually entered people's field of vision, which is the "dental pulp stem cells" that can repair cartilage damage and is expected to become the "terminator" of osteoarthritis.

Osteoarthritis know how much

"Osteoarthritis (OA)" belongs to a chronic degenerative joint disease, also known as "degenerative arthritis", which is characterized by gradual and irreversible damage/degeneration of key cartilage tissues (including articular cartilage, meniscus, etc.), accompanied by joint inflammation and joint bone changes. Patients may have joint pain, stiffness, swelling, deformity, limited activity and other manifestations, and even severe cases may be due to the loss of joint function, and there is a certain risk of disability.

Osteoarthritis is more common in the elderly, women who often wear high heels, sedentary office workers, drivers and other groups. Its occurrence may be related to aging, obesity, cold, repeated joint weight-bearing/injury and other factors.

Amazing dental pulp stem cells: from discovery to clinical application

History of research and development of dental pulp stem cells

The researchers found that teeth can form restorative dentin after injury, which suggests that there is a resident stem cell population in the dental pulp. In 2000 and 2003, dental pulp stem cells (DPSCs) were found in human permanent teeth and baby teeth respectively. Over the past 20 years, we have witnessed tremendous advances in clinical research on dental pulp stem cells.

The concept and advantages of dental pulp stem cells

Dental pulp stem cells (DPSC) are stem cells (SHED) from human deciduous teeth that can differentiate into other specific cells, such as fat cells, muscle cells, bone cells and chondrocytes (see figure below), and are a suitable source of stem cells for cell regeneration therapies such as cartilage regeneration.

Among them, human dental pulp stem cells (hDPSC) are a kind of mesenchymal stem cells isolated from dental pulp with self-renewal ability and pluripotent differentiation potential, and have the following advantages:

1、hDPSC can, under certain conditions, differentiate into a variety of types of tissue cells, contribute to the regeneration of hyalocartilage and fibrocartilage.

2、compared with traditional mesenchymal stem cells (MSC), hDPSC can secrete a variety of immune factors (such as transforming growth factor β1 (TGFβ1), hepatocyte growth factor (HGF)), and has strong immunomodulatory properties.

3、the preparation of hDPSC is less invasive than other MSCS and more convenient to use.

4、the infusion of hDPSC has a good effect on maintaining bone homeostasis, and is expected to become an effective tool for the treatment of osteoarthritis, rheumatoid arthritis, osteoporosis and other bone diseases.

What are the traditional treatments for osteoarthritis?

Drug therapy

1、local medication: the symptoms of mild can be local topical non-steroidal anti-inflammatory drugs (NSAIDs) ointment, latex agent, etc., to relieve the symptoms of local joint pain; If the symptoms are slightly severe, drugs such as hyaluronic acid and corticosteroids can be injected into the joint cavity to relieve pain, among which hyaluronic acid can also lubricate the joint and protect the joint cartilage.

2、Systemic medication: Commonly used include oral non-steroidal anti-inflammatory analgesics (such as etacoxib, celeoxib, etc.), or take cartilage protectants (such as glucosamine, etc.) to relieve symptoms.

Other non-surgical treatment methods

1、physical therapy: commonly including massage, acupuncture, heat therapy, etc., to promote local blood circulation, reduce inflammation.

2、general treatment: patients with osteoarthritis should try to reduce long-term running, jumping, excessive climbing stairs and other unreasonable movements; At the same time, adequate rest is required; Those with large weight base should lose weight appropriately.

Surgical treatment

If the above treatment is ineffective and the symptoms are more severe, surgical treatment such as knee replacement can be considered. However, surgical treatment also has disadvantages such as large trauma, difficulty in locating the prosthesis, and greater pain. Therefore, it is urgent to develop new treatment methods with less trauma and better effect than non-surgical treatment.

Why can dental pulp stem cells treat osteoarthritis?

Dental pulp stem cells can inhibit the activation of macrophages in vitro osteoarthritis

Dental pulp stem cells (hDPSCs) can significantly inhibit the expression of inflammatory molecules CD11b and CD86 in osteoarthritis macrophages, and reduce the number of macrophages in osteoarthritis (see Figure b below).

Inhibition of osteoarthritis macrophages in the absence of intercellular contact

Dental pulp stem cells block mRNA and secretion levels of macrophage-derived immune factors (TNF-α, IL-12b). And increased IL-10 expression in the absence of direct cell-to-cell contact (see Figure C below).

Osteoarthritis macrophages were partially inhibited by inactivating the MAPK pathway

The p38/MAPK, ERK/MAPK, JNK/SAPK pathways in macrophages are significantly activated in A time-dependent manner by the patient's synovial fluid (OASF), and dental pulp stem cells can partially inhibit macrophages in osteoarthritis by inactivating these MAPK pathways in macrophages (see Figure A below).

Dental pulp stem cells can reduce the damage of articular cartilage

Preclinical studies showed that 10 weeks after the injection of dental pulp stem cells (hDPSC), the results showed:

1、Degree of joint damage and repair: The articular surface was smoother in the hDPSC treated group than in the untreated group. In addition, no significant articular cartilage injury was observed in the hDPSC group, while large osteophytes were observed around the tibial plate in the untreated group.

2、Histological results: HE staining showed that hDPSC administration reduced tissue erosion in the sharp joints of OA (see figure below).

3、Pathology score: Quantitatively, the high hDPSC group had significantly lower pathology scores than the other two experimental groups (see figure below).

Small series message

Osteoarthritis is a complex disease involving the whole joint. As the disease progresses, it not only causes cartilage damage, but also may involve many tissues such as synovium, ligament and tendon. Traditional non-surgical treatment has limited efficacy and can not prevent the progression of the disease. Although knee replacement can solve the problem from the root, but the trauma is larger, the recovery is slow, and it is not suitable for all serious patients.

The stem cell therapy represented by dental pulp stem cells helps delay and control the progression of the disease, promote the regeneration of joint tissue, or will create a new chapter in the treatment of osteoarthritis!

Reference material：

[1]Mahdavi-Jouibari F,et al.Hopes and opportunities of stem cells from human exfoliated deciduous teeth (SHED) in cartilage tissue regeneration[J].Frontiers in Bioengineering and Biotechnology,2023, 11: 1021024.

https://www.frontiersin.org/articles/10.3389/fbioe.2023.1021024/full

[2]Li P L,et al.Clinical-grade human dental pulp stem cells suppressed the activation of osteoarthritic macrophages and attenuated cartilaginous damage in a rabbit osteoarthritis model[J].Stem Cell Research & Therapy, 2021, 12(1): 260.

https://stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02353-2

[3]https://www.stemsave.com/StemsaveBlogs/index?p=osteoarthritis-treatment-utilizing-dental-pulp-stem-cells