What are the two approaches to stem cell therapy for arthritis?

There are two potential approaches of stem cell-based cartilage repair and regeneration. The first is ex vivo cartilage tissue engineering, in which a replacement tissue is constructed in vitro – meaning outside the body in a laboratory using stem cells combined with scaffold using specific environmental stimuli. embryonic-stem-cell

The second is in vivo cartilage regeneration via stem cell therapy using its anti-inflammatory and immunosuppressive effects.  Stem cells are concentrated and injected locally into the affected joint. Stem cells can be applied systematically as well. So… which is better? Find out in our next episodes.

Great video…  http://youtu.be/ESeleN5WqJ0

Are all stem cells alike?

Although stem cells isolated from different tissues show similar physical characteristics, it is not clear whether these are the same stem cells, and they clearly show different abilities as far as proliferation and differentiation potential in response to stimulation with various growth factors.msc20

A study that compared human stem cells derived from bone marrow, periosteum, synovium (joint lining), muscle, and fat revealed that synovium-derived stem cells had the highest capacity for cartilage transformation, followed by bone marrow-derived and periosteum-derived stem cells. So clearly… there is a difference among stem cells.

This difference is important since some stem cells may be better suited for arthritis treatment than others.

Great video…  http://youtu.be/Qq3bpWXt8w0

Could this possibly be the ideal treatment system for osteoarthritis cartilage repair?

Is there an ideal repair system for osteoarthritis?  Mesenchymal stem cells (MSCs) are the non-blood-derived stem cells found in various adult tissues.  They have the following desirable properties: they are easy to obtain; they grow rapidly in vitro while maintaining their differentiation potential; this characteristic allows for culture expansion to get larger quantities for therapeutic use.  MSCs also have potent immunosuppressive and anti-inflammatory effects. Also, by secreting various growth factors, MSCs can influence the joint environment and exert protective effects.mesenchymal-stem-cell

In addition, MSCs have the ability to proliferate in an uncommitted state while retaining the potential to differentiate along various cell lines such as cartilage, bone, and fat in response to appropriate stimuli.

There a number of issues though in how best to harness the potential of these remarkable cells. Stay tuned!

Here’s the video…http://youtu.be/EMU3i7NgmUk

Is mosaicplasty effective for osteoarthritis?

mosaicplastyOne 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.

 

Great video…  http://youtu.be/SYxqajicO_E

 

Why is microfracture not acceptable for treating osteoarthritis!

Some orthopedic surgeons feel  that -microfracture- punching a lot of holes  in a joint is needed to get a good result.

microfracture_0One 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.

Repairing cartilage in osteoarthritis… the role of stem cell matrix

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.
msc5
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.

Great video…
http://youtu.be/oGpcLAuaW04

Why is knee cartilage so hard to repair? Even stem cells need help …

Rebuilding cartilage isn’t like building a house.

Damaged cartilage in the adult has a limited capacity to repair itself for the following reasons:

cartilage-damage1. There are no blood vessels

2. There are very few cartilage cells – chondrocytes- available to make new cartilage

3. The few available chondrocytes don’t multiply nor do they travel

4. The cartilage matrix- the “stuff” that makes up most of cartilage turns over very slowly

5. There are no stem cells to make new cartilage

6. The osteoarthritic joint is a hostile environment that makes stem cell differentiation and growth difficult.

7.Chronic inflammation may suppress stem cell transformation into cartilage

Here’s a great video…

 

Why stem cell “injections” don’t work!

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…

bone-marrow-stem-cellWrong!  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.

 

Here’s a great video…

Which is better for cartilage repair…stem cells or chondrocytes?

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.

mscMesenchymal 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.

Great video
http://youtu.be/i3SfWSRqPeQ

Can you heal damaged cartilage? … maybe… with stem cell help!

When joint cartilage is damaged for any reason, it forms cracks,

called fibrillations.  If severe enough,  cartilage damage can expose

underlying bone.  This is called subchondral bone.

Why does this happen?  Well… it’s because cartilage

lacks a blood supply.  It can’t provide reparative 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.

Chondrocytes also don’t multiply very fast.

So… bottom line, once cartilage is injured, unless something is

done to provide it with cells to heal, it will continue to degrade.

This is the bad news.

msc13 The good news is that stem cells can

repair cartilage damage when administered properly.

Great video…

 

For more information contact the Arthritis Treatment Center

Cartilage repair and stem cell scaffolds

Stem cell arthritis treatment depends on a number of important factors.

These include the mesenchymal stem cells themselves, growth factors, and a scaffold.

Stem cell therapy for arthritis requires all of these to be successful.

The stem cells and growth factors are self explanatory.

The scaffolds are a critical piece of the machinery.

stem cell scaffoldPeptides are amino acids which are the building blocks of proteins.

They can be assembled into scaffolds and have the advantages of

being both reproducible as well as functional.

Great video

For more information contact the Arthritis Treatment Center

 

Are synthetic scaffolds the key to stem cell cartilage repair for osteoarthritis?

Synthetics have the advantage of known rates of degradation, ability to keep shape, and reproducibility.

synthetic-scaffoldsThe down side is that the adhesiveness of stem cells may not be as good as natural materials.

Examples of these synthetic materials include various polymers such as

poly lactic-co-glycolic acid and poly ethylene glycol. Initial studies using

these materials as scaffolds has looked very promising.

Good video…

http://youtu.be/yN3w1p7NNIA

For more information contact the Arthritis Treatment Center

 

Stem cell knee repair… sugar as a scaffold

msc-8_0The 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.

Great video…

For more information contact the Arthritis Treatment Center

 

Why cartilage injury is so devastating!

cartilage-damageWhen 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.

The end result is arthritis…

Irreversible… or is it?

Great video…

http://youtu.be/yOfis8wS9Ow

For more information contact the Arthritis Treatment Center

Natural biomaterial scaffolding for stem cells- collagen, fibrin, silk

There are a number of natural biomaterials that have been used in experiments in tissue engineering.

Protein-based compounds include collagen, fibrin, fibrinogen, and silk.  Collagen seems to be the most

popular of these.  It can be transformed into a 3 dimensional matrix.  Stem cells are attracted to the

msc5scaffold and form blood vessels inside it.  Multiple studies have demonstrated that the use of these 3-D

collagen scaffolds along with stem cell seeding may have utility in the construction of ligaments, cartilage,

and bone. Fibrin, while not studied as much as collagen, also appears to have promise. Silk, used as a

3-D scaffold also has promise. Meinel and colleagues demonstrated that human mesenchymal stem

cells combined with silk scaffolds produced more cartilage than comparable collagen 3D scaffolds.

Silk has tensile strength that makes it attractive for engineering connective tissue.

Great video… http://youtu.be/62I_VhTVAx4

For more information contact the Arthritis Treatment Center

So…cartilage… what is it? And why is it so important?

Cartilage is a highly specialized tissue that protects the ends of long bones

from shear forces exerted by mechanical loads.  It also reduces joint friction.

Cartilage consists of cells called chondrocytes that are situated inside an

extracellular matrix which is made up of collagen which gives cartilage shape

and strength and proteoglycans that give cartilage the capacity to resist compression.

To get a good idea of what cartilage looks like, picture grapes inside a Jello mold.

cartilage_0

Cartilage has no nerves and no blood vessels.

When cartilage is damaged it has no capacity to repair itself.

That’s the BIG problem!

Great video…

http://youtu.be/yuDv4Xfd0lw

For more information contact the Arthritis Treatment Center

3-D Printer Makes Stem Cells!

From the Institute of Physics…

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.

msc11In 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.

Great video…

 http://youtu.be/PAbi5oHtacQ

For more information contact the Arthritis Treatment Center

Plasticity… How does that Help You If You Have Osteoarthritis of the Knee?

The blood contains cells with many forms and functions.

The ultimate source of these cells is called the hematopoetic

stem cell or HSC for short. One essential feature of an HSC is

self- renewal, the ability to divide and still remain a stem cell.

 

HSCs can also differentiate into more mature cells and this

transformation is conducted through a complex process

driven by protein messengers, called cytokines as well as by

growth factors.  The best known source for HSCs is

bone marrow. Along with HScs in the marrow are other stem

cells, the mesenchymal stem cells or MSCs.

msc10

Multiple experimentshave shown that HSCs are very plastic,

meaning they can be coaxed into helping with the regeneration

and repair of non-blood tissue. This has spawned the idea that “adult”

HSCs and MSCs, if placed in the proper environment

can serve as a “repair shop” for connective tissues such

as cartilage, muscle, and tendon, ligament, and bone.

Great video…

 

For more information contact the Arthritis Treatment Center

Historical perspectives on stem cells

Work by Friedenstein and colleagues

published in the 1970’s provided groundbreaking

information on the potential  for bone marrow cells

to differentiate into stem cells.

What the investigators did was to culture bone

marrow cells.  bone-marrow-stem-cell

They then removed cells that didn’t appear

to adhere to each other.  After further culture, they

found that the most adherent cells were spindle

shaped and resembled cartilage and bone.

Other groups confirmed the findings and they found

that these cells were multipotent and could

differentiate into bone cells, cartilage cells,

fat cells, and muscle cells.  The name they gave

to these multipotent cells was “mesenchymal stem cells.”

And the rest is history…

A video reiteration…

http://youtu.be/KNVPo-RfkOA

For more information go to Arthritis Treatment Center

Where are mesenchymal stem cells found?

msc9Mesenchymal stem cells, the cells that have the potential to repair

are located in a number of areas including deciduous teeth (baby teeth),

the periosteum (the surface) of bone, fat, bone marrow, and the synovium-

the lining of joints.

A study published in Arthritis and Rheumatism showed that the stem cells

found in the synovial membrane were able to proliferate

in culture and may maintain their differentiation potential.

The authors concluded these synovial membrane stem cells

may play a regenerative role in arthritis.

Other studies have demonstrated the same properties for different tissues.

Nice video…

http://youtu.be/Rj1WHCpG-Gw

For more information go to Arthritis Treatment Center