One way that surgeons use to repair cartilage is like plugging in an appliance. Mosaicplasty- or osteochondral transplantation, is a procedure where osteochondral plugs (plugs of cartilage and underlying bone) are taken from a non-weight-bearing area of the knee and plugged into a damaged area. The problem is that the donor site continues to hurt for a long time, and many chondrocytes-cartilage cells- die at the margins of the plug.
Some orthopedic surgeons feel that -microfracture- punching a lot of holes in a joint is needed to get a good result.
One attempt to make new cartilage, particularly in younger individuals has been microfracture. This technique involves drilling holes and fracturing the subchondral bone multiple times. What occurs then is that fibrin clots form, blood vessels invade, and a few stem cells are recruited from the fractured bone marrow resulting in scar tissue that is biomechanically inferior to hyaline cartilage. As a result it wears away more quickly.
This is not considered a good therapy for osteoarthritis for many reasons including the long term recuperation, the morbidity surrounding the procedure itself, and the production of poor quality fibrocartilage instead of better quality hyaline cartilage.
Stem cells need something to cling to if they’re going to become cartilage. The something is called a matrix or scaffold. So what are the ideal properties of a scaffold? Tissue engineering… cartilage repair for osteoarthritis treatment is extremely involved. A good scaffold or matrix is important.
They need to be bio-compatible so inflammation doesn’t damage the host. Second, they need to have a three dimensional shape to allow the cell differentiation and multiplication. Third, they need to be porous to allow diffusion of nutrients and oxygen as well as passage of cells. Fourth, the scaffold should permit adhesion or sticking of the stem cells to it. Fifth, the scaffold should participate in the growth process by releasing growth factors. Sixth, the matrix should stick to the host tissue. Seventh, the scaffold must maintain its shape during the growth phase, and also degrade during the remodeling phase. Eighth, the scaffold should be able to be implanted using minimally invasive procedures.
One of the popular misconceptions is that just shooting some stem cells into a joint will heal osteoarthritis… that that is all the arthritis treatment needed…
Wrong! Nothing could be further from the truth. Here’s why…
The success of cartilage regeneration with stem cells rests on a four-legged stool. The first, of course, is the stem cell preparation. The second are the multiple growth factors needed to stimulate stem cell growth and proliferation. The third is a scaffold for the stem cells to adhere to. If the scaffold doesn’t allow stem cell adherence and help supply the proper nutrients, the stem cells will die. The fourth is injury induction in the area that needs to be healed. Without a target, the stem cells don’t know where to go. Without all four critical factors, the procedure is not going to work.
Much has been made of the role of chondrocyte repair in the orthopedic literature. While results have been encouraging for smaller full thickness lesions in young athletes, the role of chondrocytes in treating osteoarthritis is less clear. And as further work is done with chondrocytes, optimism has waned because of complications related to the procedures, long time recovery period, and more than expected chondrocyte death.
Mesenchymal stem cells are easy to obtain and proliferate-multiply- rapidly, given the right growth factors. They can be found in bone marrow, muscle, fat, periosteum, umbilical cord blood, synovium, and placenta. In addition, they can be coaxed into becoming a number of different types of tissue including muscle, cartilage, and bone. Besides escaping from the immune regulation of the host, they also have immunoregulatory effects. Multiple studies have shown their ability to differentiate into good quality cartilage in the presence of osteoarthritic joints.
The key constituents of a system required for knee osteoarthritis stem cell treatment are stem cells, growth factors, and a scaffold. Polysaccharides are sugars that play an important role in the structure of matrix material- the stuff that holds cells together. These polysaccharides are being studied as possible stem cell frameworks for osteoarthritis treatment. These polysaccharides can be turned into gels rapidly and therefore can be injected into a damaged joint easily. Among these are agarose and alginate which are derived from algae. Hyaluronic acid is already being used as a palliative osteoarthritis treatment but is also considered a possible stem cell additive.
When joint cartilage is damaged, it begins to degrade and form cracks, called fibrillations. If severe enough, the cartilage damage can expose underlying bone. Why does this happen. Well… it’s because cartilage lacks a blood supply. It can’t supply stem cells from the blood or bone marrow to help with healing. Even cartilage cells-the chondrocytes- really can’t move to help since they’re trapped inside their matrix. So… bottom line, once cartilage is injured, unless something is done to provide it with cells to heal, it will continue to degrade.
A team of researchers from Scotland has used a novel 3D printing technique to arrange human embryonic stem cells (hESCs) for the very first time. It is hoped that this breakthrough, which was published in the journal Biofabrication, will allow three-dimensional tissues and structures to be created using hESCs, which could, amongst other things, speed up and improve the process of drug testing.
In the field of biofabrication, great advances have been made in recent years towards fabricating three-dimensional tissues and organs by combining artificial solid structures and cells; however, in the majority of these studies, animal cells have been used to test the different printing methods which are used to produce the structures.
Co-author of the study, Dr Will Wenmiao Shu, from Heriot-Watt University, said: “To the best of our knowledge, this is the first time that hESCs have been printed. The generation of 3D structures from hESCs will allow us to create more accurate human tissue models which are essential for in vitro drug development and toxicity-testing. Since the majority of drug discovery is targeting human disease, it makes sense to use human tissues.”
In the longer term, this new method of printing may also pave the way for incorporating hESCs into artificially created organs and tissues ready for transplantation into patients suffering from a variety of diseases.
Comment: This may have a huge impact on the ability to treat diseases such as arthritis.
Investigators are trying to understand two important properties of stem cells:
why can embryonic stem cells multiply for a year or more in the laboratory without differentiating, but most non-embryonic stem cells cannot; and
what are the factors in living organisms that normally regulate stem cell proliferation and self-renewal?
Finding the answers to these questions may make it possible to understand how cell proliferation is regulated during normal embryonic development or during the abnormal cell division that leads to cancer. This information will also help scientists grow embryonic and non-embryonic stem cells more efficiently in the laboratory.
And this will help us more clearly understand how to use stem cells more safely in human arthritis and osteoarthritis treatment.
Cartilage damage is irreversible. To date, only reconstructive surgical procedures such as joint replacement are the only option available for significant cartilage loss.
Cell therapy, using transplantable stem cells with scaffolds, can possible regenerate new cartilage matrix. The potential of mesenchymal stem cells to differentiate into chondrocytes (cartilage cells) with the aid of the proper environment and growth factors makes these cells very attractive for tissue engineering purposes.
The combination of three key ingredients… stem cells, growth factors, and a framework is required.