STEM CELL THERAPY

Aside from many of the treatments listed on this website, publications have highlighted the need for a new treatment [2].  In addition, current existing medical treatments for osteoarthritis aim to suppress associated symptoms but many of them do not repair the damaged tissue. Stem cell therapy is now considered an alternative therapy that can potentially treat the underlying cause of OA by repairing the worn cartilage in patient’s joints as well as providing pain relief [42].

Overall, there is a misconception of the words “Stem Cells”. When mentioned, the most common relation of the terms “stem cell” goes back to aborted baby foetus for the purposes of cloning. This is not the case.

Stem cells are not black and white, the treatment protocols vary significantly.

Stem cells have evolved significantly beyond their initial years prior to the 1990’s. 20+ years in development, we know now stem cell sources can be obtained from right about anywhere in the human body. Aborted foetuses are becoming phased out of clinical use due to the unethical nature of obtaining the cells.

Types of Stem Cell Treatments

Currently there are 4 main types of Stem Cell Therapies available

  1. Body Fat (Adipose Tissue)
  2. Bone Marrow
  3. Blood
  4. Cord Blood or Fetal Cells (Embryonic Cells) – NOT IN AUSTRALIA

Top 3 methods obtained provide us with what is generally now known as “Adult Stem Cells”. Typically adult stem cells are considered ethically less dangerous compared to embryonic stem cells [46]. The Australian medical regulations are strict, ethical guidelines must be met. Individuals can rest assured Embryonic Cells will not be used in clinical patient applications.

Cell Separation Methods

The cell separation method is extremely important. There are 3 main methods of cell separation as listed below;

  • Enzymatic separation
  • Mechanical disruption
  • Ultrasound assisted separation

However, it is not as simple as this. There are thousands of varying protocols that expand on these methods.

Mechanical and ultrasound (external only) separation methods are the safest ways to split stem cells from tissue since there are no other agents included in the process. Collagenase and lecithin are common enzyme based separation methods used. Enzymes like collagenase are used to breakdown connective tissue; this is how they separate stem cells from other tissues. There is a potential for this enzyme to be left-over in the stem cell injection process, this could lead to destruction of connective tissue within the joint [42]. Therefore mechanical or ultrasound cell separation is considered to be less manipulative and safer.

Cultured or Fresh Cells?

The next step in understanding stem cell treatments is grasping the culturing process. When the tissues are broken down, the complete stromal vascular fraction (SVF) is left behind. The SVF contains multiple cell strands that are beneficial to our bodies, such as;

  • mesenchymal stem cells & haematopoietic stem cells
  • pericytes – adipocytes – fibroblasts – endothelial cells
  • vascular progenitors
  • endothelial progenitor cells – haematopoietic progenitors

It is important to understand, SVF has the ability to home to areas that are inflamed in the human body. Areas of inflammation are typically areas that are damaged and require repairs. Therefore, SVF can repair multiple tissues and multiple areas with a single treatment [42], [52], [55].

From this point, the technician can decide to either use the whole SVF or the technician can separate just 1 type of stem cells from the SVF and grow them in a laboratory to multiply the cell numbers. This is the process known as the cell culturing.

Culturing cells may create DNA replication stress, the effect of replication stress can lead to incomplete DNA replication. Furthermore, the process of replication stress can drive what is known as tumorigenesis and lead to genetic mutations within the cells [49], [57]. Once cells have been cultured, their homing ability becomes significantly compromised [58]. This means their repairs are best targeted to a localised area, addressing a simple and specific issue.

Stem cells do not need to be cultured unless there is a specific single purpose they are being used for OR the cell numbers are very low to begin with. In many cases, the risks of using cultured cells can be avoided by utilising a method of cell collection that provides very high numbers of total SVF.

The final step is to define “autologous” and “allogeneic”. This is simple, autologous means they are your own cells, taken from your body and injected back into you. Allogeneic refers to cells that are taken from someone else and donor matched to the next patient. Autologous is much safer since there are no risks of immune rejection.

Body Fat Stem Cells (Adipose)

Adipose simply indicates these cells are taken from your body fat. These stem cells are now being used as an alternative treatment in the field of arthritis as well as other disorders that involve the bone, tendons and ligaments. The stem cells from body fat are currently the most desirable method to obtain these cells due to their easy of accessibility and their availability in large quantities [42].

The quantity of cells have shown to be important, one  blinded randomized clinical trial indicated that higher number of stem cells can result in improved cartilage growth [43].

In the treatment of osteoarthritis, stem cells possess the ability regenerate the damaged cartilage, resolve inflammation, and repair the surrounding supporting structure of the joints such as synovial membranes, blood vessels, tendons and ligament [42].  The primary outcome in assessed clinical publications is to control pain, improve function and formally repair cartilage where repairs are possible.

Multiple studies confirm, significant reduction in pain, significant improvements in joint function, quality of life and cartilage growth. The studies also confirm minimal side effects due to the treatment. One of the meta-analysis papers conclude stem cells from body fat have significant potential for the treatment of osteoarthritis but the population assessed has had multiple different treatments. The paper does not confidently indicate stem cells are the sole factor behind all of the improvements and it suggests larger, more consistent trials are needed for conclusive analysis [44].

The most recent systematic review that took place in 2017 indicates autologous adipose SVF can be worthwhile to try in individuals for whom medical treatment has failed and for whom surgical options are not available [42].

Overall, stem cells obtained from body fat have shown to be very effective, safe and superior compared to bone marrow cells [42], [42], [44].

Bone Marrow Stem Cells

Cells taken from the patient’s bone marrow can be extremely useful in situations where the patient is lacking adequate body fat stores. Studies look with joint disorders such as avascular necrosis, after an average of seven years post treatment with bone marrow cells, 94 of the 116 patients did not require a joint replacement [47].  In another controlled study with 13 patients suffering from bone necrosis of the femoral head, the patients whom received stem cells showed significant reduction of pain and disease progression as opposed to patients who received placebo [47].

Blood Derived Stem Cells

Blood derived stem cells are usually known as the “Cheap Method” of obtaining stem cells. As a general note, the stem cell counts in your blood are much lower than Bone Marrow and significantly less than Body Fat derived stem cells [50]. Therefore it is necessary to culture these cells.

The cultured cells can then be implanted back into the arthritic joint and blood derived stem cells can be effective when cultured; their main purpose will be to help a defective cartilage at the early stages of arthritis. Improvements gained from blood derived stem cells can decrease as OA progression develops past the lower grades.

Embryonic Stem Cells (Fetal Cells)

Embryonic stem cells were the very first stem cells to be discovered by James Thomson in 1988. These cells are pluripotent, meaning they can become and repair any type of cell within your body [46]. Typically obtained from cord blood, placenta or baby fetus, this classic stem cell treatment lacks control and stability due its vast nature of differentiation. This makes embryonic stem cells very powerful but not difficult to predict, therefore they are not as safe as adult stem cells [46].

Many publications confirm embryonic stem cells have potential to repair and grow cartilage, however many of these publications still focus on work that is carried out in laboratory environment, the applications are mainly based on animal models.

For example, one study found, after 15 weeks transplantation of differentiated embryonic stem cells into rats, there were no observed adverse immune responses but cartilage production had started to occur. This and many studies conclude embryonic stem cells to be efficient and clinically translatable approach for cartilage tissue regeneration for osteoarthritis [48]. However, due to their unethical obtaining methods, lack of control and possible risks associated with rejection, embryonic stem cells are thought as “overkill” for therapeutic use in treating osteoarthritis.

 

Comparison of Stem Cell Therapies

  • Bone marrow harvest can be useful if a patient is lacking body fat or they are looking to treat a small joint with minimal cost. The cheaper cost is often related to reduce operating time in comparison to liposuction of adipose tissue.
  • Cells taken from the patients’ blood can be useful in situations where patients do not want to undergo surgery, but minimal cell counts are expected. Therefore results may not be as good in comparison to superior treatments such as bone marrow or adipose [51].
  • Adipose Derived Cells in comparison with Bone Marrow Cells have similar properties of Mesenchymal Stem Cells. However, the cellular mix from adipose tissue is superior to bone marrow [55].
  • Adipose derived cells contain approximately 100-1000 fold higher stem cell counts in comparison to bone marrow derived cells. Therefore you can obtain significantly more nucleated cells from adipose tissue as compared to bone marrow [52].
  • The percentage of stem cells in bone marrow is quite low and decreases with age [53], therefore bone marrow derived cells become less appropriate in older aged patients [54].
  • Adipose can be obtained in larger volumes compared to bone marrow, therefore high cell counts are easy to achieve.
  • Adipose cells have better application in treating patient who requires treatment to multiple joints due to the higher cell counts.
  • If the patient requires “whole body approach” or treatment to many joints, adipose derived stem cells can be injected intravenously.
  • Culturing cells can be useful if there is a defect to repair, cultured cells become less useful as the joint damage becomes “overwhelming”. This specifically applies to individuals whom have become “bone on bone” in their joints. Cultured cells are not as effective as the uncultured complete cellular mix obtained from adipose tissue.
  • Embryonic cells are not necessarily required in the treatment of osteoarthritis. Great outcomes can be achieved with adipose derived stem cells.

STEM CELL CONCLUSION

In 2016, Filardo et al., reviewed 60 different Stem Cell studies and published the results in the Journal of Orthopaedic surgery. His team’s conclusion found no major side effects and considered the treatment to be safe. They confirmed improvements clinically by the patients pain levels and joint function. In addition, the observed MRI reports indicated cartilage growth. This publication did suggest further research should be carried out in this field and this is currently a working progress [51].

In 2017 Pas et al., reviewed 5 randomised trials and 1 non-randomised trial. His review observed Bone-marrow, adipose and peripheral blood stem cells. All of the randomised trials reported superior efficacy for patient outcomes in relation to pain, function and quality of life, the longest follow up was observed for 4 years. The radiological observations (MRI’s) favoured the stem cell injections and reported improved healing rates. This review also found no serious adverse events [45].

Chiari et al., advised stem cells are becoming increasingly more important in the field of regenerative medicine. These cells are already being used in a clinical setting appear to be very safe. His group concludes, stem cells have the ability to repair cartilage and joint dysfunction [46].

The most recent systematic review took place in 2017 by Pak et al., this indicates stem cell treatments can be worthwhile to try in individuals for whom medical treatment has failed and for whom surgical options are not available [42].

All of the literature reviews focus on the proven benefits of stem cell treatments for osteoarthritis; however they are all in agreeance about the lack of formal randomized trials. A few trials are not considered to be enough, the data from one trial to another ends up being completely different, even though all of the trials confirm improvements with good safety. Despite the successful results reported by these articles, stem cells have not yet  become readily accepted as a mainstream medical treatment [42], [45], [46], [51].

Further information from Macquarie Stem Cells – click here.

Read about more treatment options for osteoarthritis on this page.

 

All references can be found in our list of references page here.