Stem Cell Therapy
The promise of stem cell is becoming attractive for the one who believe that an answer to all of our problems can be found with this kind of therapy. Minimally invasive and quite simple, physicians are able to harvest from patients some pluripotent cell to introduce them in a damaged or degenerative area of the body. If you believe in the process, these injected cells will stimulate a healing process in generating new tissue. Repair will follow.
Bone marrow transplant is the most commonly used stem-cell therapy with even blood deriving from the umbilical cord has been used. We hope to be able to apply these treatments to any neurodegenerative disease or other chronic disease like diabetes and heart disease. Some scientists have bought already controversy in the field when they started to isolate and culture embryonic cells to create pluripotent stem cells especially when using cells from aborted fetuses to create human clones.
Cells can be harvested without compromising the donor site and then separated from the non-stem cell environment and rapidly “centrifuged” in machines. These cells come from the patient’s own baggage, minimizing the risk of transmission of disease or allergic reaction or rejection. Nobody will reject their own tissue.
During the last three decades, bone marrow has been used to treat conditions like Leukemia and Lymphoma because while using the current chemotherapy drugs, most of the cancerous cells are destroyed by the cytotoxic agents. Unfortunately, these agents are unable to differentiate a normal hematopoietic cell from a neoplastic cell within the bone marrow, and destroy all cells. So, it is believed that the stem cell transplant will work at reversing the destructive effect of the drugs. The new implanted cells will also generate an immune response able to facilitate the killing of the humoral cells.
In 2012, a stem cell therapeutic agent, originated from Canada (Prochymal) was used in children not responsive to steroids medication as an allogenic stem therapy based on mesenchymal stem cells (MSC) derived from bone marrow of adult donor. These cells were purified from the marrow, cultured and packaged while kept frozen prior usage.
Similarly, different hematopoietic stem cells products deriving from the umbilical cord blood were approved to treat many blood and immunological diseases. The Europeans as well approved limbal stem cells to treat burn injury to the eye.
Many orthopedic institutions have claimed a lack of funding in evaluating such way the field of regenerative medicine. In approaching degenerative arthritis, often we, orthopedists, are asked by our patients about unconventional way of treating a painful knee or hip crippling their activities. When stem cell therapy is mentioned as a mode of treatment, physicians have also to face the insurances companies hiding behind the inconclusive evidence of the science supporting the facts.
The average re-imbursement for a stem cell injection for an arthritic joint, cost Medicare more than a Total Knee Replacement itself. More, the patient may be responsible of the extra charges. A study at the NIH on more than 280 patients receiving stem cell therapy will, hopefully, in a near future bring some lights on regenerative medicine.
Stem cell therapy bring hope at the end of the tunnel. We may find a “cure” for degenerative arthritis of joints and a reparative process, rendering more mobile an adult population of “Baby boomers”. The promise of a new treatment for musculoskeletal disease and tumors with stem cell therapy is exciting but remain years away from the actual clinical trials. We must be committed to science. This mode of treatment is slowly becoming well-accepted in musculoskeletal. care. It is emerging and promising.
Stem cell are being studied for other reasons as well. Molecules and exosomes released from the stem cells are being used to make new medications. Stem cell secretome (Pancrine) produced by stem cells may be able as well to help in auto-immune and inflammatory diseases.
It requires a large numbers of high quality stem cells to perform a culture in the goal of producing a pure population of tissue specific stem-cells in-vitro. These cultures are routinely performed in thousands of laboratories worldwide and the substrate requires a dramatic adaptation for the surviving cells because they all lack an extracellular matrix. We have taken samples via arthroscopic punches from patella healthy cartilage or tibia plateau to send them to specific laboratories for in-vitro culture. Three weeks later, another arthroscopic procedure of the knee is done to implant the cultured cartilage and fill up the desired defect.
Researches have been conducted on brain degeneration like Parkinson, Amyotrophic lateral Sclerosis and Alzheimer’s diseases as well as Multiple Sclerosis. Neural stem cell become progenitor cells and then migrate within the brain to maintain the neuron population for olfaction (smell). Recently, I read on the net that the University of VA was conducting studies on the use of Ultrasound in the treatment of early patient suffering of Alzheimer’s. One will have to ask the investigators to stipulate on what criteria they allow a physician to assert a case of Alzheimer’s in a mild case of Dementia since the diagnosis is generally made on a post mortem specimen.
Patient suffering from stroke and traumatic brain injury do present with cell death. Studies in animal with spinal cord injury are also being conducted with stem cells. Unfortunately, stem cells which have studied heart conditions have shown only modest improvements in the cardiac function following the use of autologous bone marrow stem cell therapy. Adipose derived stem cells are occasionally used as well. It is not well known how the mechanism works but it is anticipated that the secretion of growth factors is enhanced, stimulating a neovascularization in the area of damaged cardiac muscle. Further studies will need to bring light on the subject.
Many discrepancies were noted in a 2014 meta-analysis using bone marrow stem cells for heart disease with major adverse reactions reported. Trials like Time, Boost 2, STEM1 to improve Left Ventricular function in people who has suffered from a myocardial infarction, has not bought any positive conclusions nor that the desired changes were noted on MRI evaluation.
In Hemato-pathology, diseases of the hematopoietic cells can be also diagnosed rendering the deficient immune system to recognize foreign antigens. Research using both hematopoietic adult stem cell and embryonic stem cells have provided some insight in the treatment of these diseases. Mature red blood cells can be generated by hematopoietic stem cells which are the precursors of red blood cells. These cells are grown together with stromal cells creating an environment that mimics the condition encountered in the bone marrow. Erythropoietin as a growth factor, can be added to help in the differentiation.
Scientists at King’s College in London, found a way to “cultivate” a complete tooth in mice and they remained confident to be able, one day, to apply the technology on humans when stem cells from a patient would be able to be implanted into the gums and generate a tooth in less than a month. The tooth will then be attached to the jawbone fully able to release chemicals stimulating nerve and blood vessels integration.
Corneal stem cells have been implanted into damaged eyes to restore vision. The cells were harvested from aborted fetus. At the Queen Victoria Hospital in Sussex, England, a team of specialists restored the sight of 30 patients in 2005. They were using adult stem cells taken from the patient itself, or a relative or even a cadaver.
People suffering from Type 1 Diabetes Mellitus has none or little functional beta cells producing Insulin in the pancreas and recently, scientists have been able coax embryonic stem cells to tum into beta cells in the lab. Once those cells transplanted, they would be able to replace the deficient beta cells in the pancreas of a diabetic patient and hopefully produce the desired insulin.
In Orthopedics, mesenchymal stem cells are injected in joints, bone and muscles. These cells derived from adult stem cells. They are used in trauma for cartilage repair, osteoarthritis, intervertebral disc surgery, rotator cuff surgery and other musculoskeletal disorders. We are actively using these specialized cell in our armamentarium in the field of tissue engineering and regenerative medicine.
Recently, I participated in a wound care course and I was surprised to see how stem cells were used to stimulate the growth of human tissues. If in an adult, most wounded tissues heal by scar tissue, the stem cells now have been recognized to stimulate the growth in human. In wounded fetal tissue, the tissue is replaced by regenerated tissue through the activities of the stem cells. Others have seeded the stem cells through the wound to stimulate differentiation in the tissue bed. This technique of seeding is still being investigated but has already gained an interest in cutaneous wounds and skin cancer.
Human embryonic stem cells have been cultured and mixed with porcine ovarian fibroblasts to stimulate a differentiation into germ cells (oocytes-spermatozoa), for gene expression analysis. Human embryonic stem cells have also been stimulated to form spermatozoid-like cell to potentially treat azoospermia. In an adult mouse, in 2012, oogonial stem cells were isolated from an adult mouse and human ovaries in the goal of forming mature oocytes with the possibility in treating Infertility. Sperm can be produced from high genetic individuals who died before reaching sexual maturity.
In patients with HIV/AIDS, the immune system is destroyed by the virus as reported by the loss of CD4 and T cells in the peripheral blood and the lymphoid tissues. Scientists have been looking at an alternative approach to boost the immune system through the implantation of autologous, gene modified hematopoietic stem cells.
Stem cells are thought to mediate repair by many mechanisms:
1- Providing an anti-inflammatory effect.
2- Recruiting other cells like endothelial progenitor cells for tissue growth.
3- Supporting the remodeling tissue
4- Inhibiting apoptosis
5- Differentiating bone from cartilage or ligament from tendon.
The efficacy of the stem cell population can be affected by the method of delivery. Stem cells have low immunogenicity but are able to secrete chemokines that alter the immune response and promote tolerance of the new tissue. The ability to grow up functional adult tissues and indefinitely in culture, creates new opportunities for drug search in humans and animals.
As we have stated, most stem cells used for regenerative therapy are generally harvested from the bone marrow or the adipose tissue. The mesenchymal stem cells are the one to differentiate them in bone, cartilage, tendons or ligaments as well as muscle or nerves. It is generally thought that bone marrow derived stem cells are preferred for bone cartilage, ligament or tendon repair.
There has been new interest in the use of extraembryonic mesenchymal stem cells from the umbilical cord, the yolk sac and the placenta of different animals which hopefully can show more differentiation in their ability to form tissues of ectodermal or endodermal origin.
There are also controversies in using human embryonic stem cells on the fact that the techniques used, require the destruction of the blastocyst. There are additional controversies on a philosophical, moral or religious basis. Other stem cells research does not destroy the human embryo and such research involve the adult stem cells and the amniotic stem cells introduced as pluripotent stem cells
The Geron Corporation was given clearance by the FDA in 2009, for the first clinical trial of an embryonic stem cell based therapy on humans. A drug “GRNOPC1” was used on people with acute spinal cord injury but the trial was discontinued. The Bio Time Cie has since acquired the right to continue the clinical trial.
Veterinarian studies performed on animals like horses, dogs and cats have benefited from the development of mesenchymal stem cell treatments in regenerative medicine to cover areas like myocardial infarction, stroke, bone and cartilage damage, osteoarthritis, muscle dystrophy in animals and humans.
Bone has a unique healing process and within four weeks of placing the scaffold, newly bone begins to integrate and mix with the old bone to provide full union in 32 weeks. Stem cells have been successfully injected in the femoral head of dogs suffering of Legg-Calve-Perthes disease or Avascular Necrosis. Autologous stem cell-based treatments for ligament, tendon osteoarthritis Osteochondrosis etc. have been successful in animal as well.
Stem cell therapy in the United States is being touted as a miracle cure for little skin defect to spinal repair. We have tried to oversee for you, some areas where this therapy is being applied. Promising studies in knee degenerative arthritis are bringing scientific backing to the benefits of such treatment. Osteoarthritis being a major cause of disability, a combination of stem cell preparations is seen on the market with the goal of maintaining and heal tissues by replenishing damaged and dying cells.
It is expected that by the year 2030, 3 million Americans will undergo Total Knee Replacement.
If stem cell therapy is able to reduce pain. by repair of damaged cartilage, the baby boomers will be able to improve their quality of life and hopefully, avoid any surgical treatment. Adult stem cells can be extracted from bone marrow or fat though simple methods and injected under image guidance to the joint with successful results. There is ongoing research to fine tune the technique. This is a noninvasive procedure, and rarely painful.
The average cost for a stem cell treatment is between 3500 and 5000 dollars. Most insurance companies will not cover the cost of the injections but this will start to change when the effectiveness of such procedure can be proven. The procedure is done in one visit and the injections can last a little less than 3 hours.
In conclusion, osteoarthritis is the main cause of joint pain in humans and animals. Horses and dogs are usually affected by this disease during their lifetime. If mesenchymal stem cells are still being researched, adipose-derived mesenchymal cells have already made an impact in the treatment of osteoarthritis because of their noninvasive harvesting. For muscle repairs, stem cells are also successfully used but for the heart, after myocardial infarction, more work will be needed to generate cardio-myocytes more contractile, once they are produced by the mesenchymal cells.
Veterinarians have used primary mesenchymal stem cells in spinal cord trauma. This kind of treatment stimulates scar tissue at the site of the injury, allowing the dogs to be able to support their own weight while recovering.
Stem cell therapy and other biological interventions are becoming an accepted part of musculoskeletal care. We will have to be ready to offer such alternative to our patients. Stem cell therapy is there to stay and you better get use to it.
Maxime Coles MD
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