MANAGEMENT OF OSTEOARTHRITIS WITH STEM CELLS

How stem cells modify OA pathology?


1. Along with their immunomodulatory and differentiation potential, Mesenchymal stem cells
(MSCs) have been shown to express essential cytokines including Transforming Growth Factor
beta (TGFβ), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF)
and an array of bioactive molecules that stimulate local tissue repair and regeneration.

2. MSCs are able to form cells of the mesodermal lineage, being able to differentiate towards

osteoblasts, chondrocytes and adipocytes.

What is Osteoarthritis (OA)?

Osteoarthritis is a leading cause of pain and disability across the world. With an aging population its
prevalence is likely to further increase.
OA is characterized by progressive and irreversible cartilage degeneration and osseous overgrowth.
The capacity of articular cartilage to repair is inherently poor, with the relative avascularity of cartilage,
and hence lack of systemic regulation, likely leading to an ineffective healing and reparative response.
Structurally the changes of OA are observed as combinations of the following:
• Loss of cartilage thickness
• Peri-articular bone formation (osteophytes)
• Subchondral sclerosis
• Cyst formation and,
• Peri-articular tissue changes (i.e., synovitis)

The symptoms of OA include joint pain, swelling, tenderness, stiffness, and sometimes locking, which
may lead to disability and severely affect the life quality of patients.

Current line of management of OA:

There are mainly five kinds of medications commonly used in today’s clinical treatment of OA:
• Acetaminophen
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Opioid analgesics
• Serotonin–norepinephrine reuptake inhibitors (SNRIs) and,
• Intra-articular injections of corticosteroids and hyaluronic acid

Current medical treatment strategies for OA are aimed at pain reduction and symptom control rather
than disease modification. These pharmaceutical treatments are limited and can have unwanted side
effects.

Methods used for repair of articular cartilage lesions include autologous chondrocyte transplantation,
microfracture, and mosaicplasty. These techniques are, however, limited to the repair of focal defects
and consequently lacking a reparative technique for the more diffuse pathology of OA.

Surgical total knee replacement (TKR) is the current accepted treatment of choice for symptomatic
knee OA that is not controlled by traditional conservative therapies. But Total knee replacements are
not without significant complication. Many patients continue to have knee pain and other problems
post TKR. Significant complications such as death, pulmonary embolism and infections requiring
readmission to hospital are not rare with TKR.

Sources of mesenchymal stem cells

Mesenchymal stem cells are found throughout the adult body – hence they are often referred to as
mesenchymal stromal cells. Several different tissues have been explored including bone marrow,
adipose tissue, and umbilical cord tissue (Wharton’s jelly).
Traditionally bone marrow has been used as a source of MSCs. In comparison, human adipose tissue,
due to its ease of harvest and the relative abundance of MSCs is being increasingly used for autologous
therapies.

Types of Stem cells used in Treatment of OA:

• Embryonic stem cells (ESCs)
• Induced pluripotent stem cells (iPSCs)

iPSCs are more applicable than ESCs, as they can be derived from more donor tissues with less
immunorejection, and have less ethical controversy.

Delivery modes for mesenchymal stem cells

A crucial requirement for MSC-based OA therapy is the delivery of the cells to the defect site. Direct
intra-articular injection might be possible in early stages of the disease when the defect is restricted to the cartilage layer, whereas a scaffold or matrix of some kind would be required to support the MCSs in cases where the subchondral bone is exposed over large areas.

An ability to migrate to sites of injury, inhibit pro-inflammatory pathways and promote tissue repair
through release of anabolic cytokines and direct differentiation into an array of specialized connective
tissue cells, has led to renewed focus on MSCs in the area of regenerative medicine.

FURTHER READINGS:

1. http://www.arthritisresearchuk.org/arthritis-information/arthritis-today-magazine/165-summer-2014/could-stemcell-
therapies-be-the-answer-for-osteoarthritis.aspx
2. http://www.arthritis-health.com/treatment/injections/stem-cell-therapy-arthritis

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