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FAQ Stems Cells/Stem Cell Therapy

  1. What is a stem cell?

Stem cells are our own body’s ancestor cells which can – in theory – become building cells for any organ of the body. Stem cells begin to develop as soon as the blastula, that little ball of becoming-baby cells in the womb starts to elongate and differentiate into organs.

  1. What is the purpose of stem cells?

When the body is injured, it puts out certain “I am hurt” signals called inflammatory cytokines which attract potentially healing cells through the blood stream to the area of injury. In theory, every area of the body has access to these cells, since every area of the body except the cornea has its own blood supply. Every organ of the body so far investigated has its own version of stem cells – even the teeth, although so far the process has been limited to the spontaneous replacement of “baby” teeth with “adult” teeth. We have not yet seen re-growth of an adult tooth.

So far stem cell therapy in one form or another has been used medically for a multitude of conditions, with variable success.

Injection into painful arthritic joints has the most experience behind it – both animal experiments and human treatment.

Stem cells have been injected into painful knee joints, even sometimes with injured or missing cartilage, with excellent results in both pain reduction and restoration of the cartilage.[1]

  1. Where and how are stem cells produced?

Every organ tested to date has shown to have a certain number of organ-specific cells which can be coaxed or forced into becoming mature cells of that organ – kidney for kidney, muscle for muscle, even nerve for nerve/brain.

Some places in the body have more immature cells which can become (differentiate) into multiple types of cells. Cells in the bone marrow can be persuaded to become blood cells of many types. They have also been shown to produce muscle, or cartilage, or bone, or even nerve cells. Cells in the fatty tissues of the body produce cartilage, bone and nerve cells as well.

  1. How does the healing process occur?

The healing process often starts by injury to a blood vessel. Every place in the body – except the cornea –is well supplied with capillaries. Some of the capillaries are so small that red blood cells have to squeeze themselves into interesting shapes in order to get through the tiny tunnel. Platelets are attracted to the site of injury. They are activated by compounds secreted by injured tissues, producing factors which induce clotting at the area of wounding. Thus when we are wounded, most of the time we do not bleed to death, but rather begin to heal the wound immediately.

Why do we need to treat anything with stem cells? Why doesn’t the body just do its thing and heal?

Why is a big question. Often the body does “do its thing”, for example when the skin is cut, the body closes the wound – albeit with a scar. When a bone is fractured, the body speeds up building of bone at the site of the fracture, and healing occurs.

When the normal healing process does not occur, we can be of assistance by encouraging healing through a medical procedure called stem cell therapy.

  1. What is the procedure for “stem cell therapy”?

Stem cells are harvested from various places in the body – blood, adipose (fat) tissue and/or bone marrow. The tissues are then washed to eliminate anything used in the harvesting procedure that is not made by the body. The washed stem cells may then be inhaled into the lungs using a nebulizer (in the case of severe COPD) or re-injected into the body in various locations such as painful joints, injured ligaments or tendons.

One excellent method, currently under negative scrutiny by the FDA, involves separating the stem cell containing fraction of adipose tissue from the fat cells themselves, and infusing only the stem cell fraction (called the Stromal-Vascular Fraction or SVF) with its pericytes – cells which adhere to blood vessels all over the body. These pericytes migrate to areas of injury when the call is sent out by the platelets. Unfortunately the FDA seems to be of a mind to consider the SVF cells to be a drug rather than a body part, and therefore subject to their lengthy and expensive “Investigational New Drug” application process. For more information about this issue, click here and here.

  1. Does stem cell therapy hurt?

Drawing blood requires the use of a needle – just like any other blood draw you would do at a regular lab.

Harvesting adipose tissue is a little more complex – but not a whole lot. The local anesthetic stings, but then blocks pain nerves, so generally only pressure in the fat layer of the abdomen is felt. You wear a compression bandage for a couple of days, so as to minimize any potential bleeding.

Harvesting bone marrow also requires the use of a local anesthetic to deaden the skin and the periosteum (covering) of the bone from which marrow is withdrawn. You will feel a pulling sensation as bone marrow is withdrawn into the harvesting syringe.

  1. If I am having therapy on a painful arthritic joint, how soon can I use the treated extremity?

After the procedure we encourage gradually increasing use of the extremity. We recommend physical therapy to help with gradually increasing use of the involved joint – including strengthening exercises to help build up both joint motility and flexibility.

If a weight bearing joint like knee or hip is injected, we discourage weight bearing for the first two days to allow for maximum healing. After the first two days, gradual weight bearing is permitted. By the end of two weeks there is full weight bearing, and you should be experiencing significant pain relief.

If the joint is the shoulder or wrist, we discourage use of the treated arm for two days, followed by gradually increasing use with both range-of-motion and strengthening exercises.

  1. How soon might I see an effect, if I decide to do cell based therapy?

Healing begins almost immediately, as the body’s own healing cells begin to release their growth factors. There may be some soreness in an injected joint during the first 2-3 days as those growth factors begin to call out the body’s healing mechanisms. Or there may be relief of pain. Everyone has a slightly different response. In any case, most people will begin to feel relief within two to three weeks. The relief may not be 100%, but almost always pain is substantially less.

One study from Australia reported that symptomatic improvement was achieved within one week of the first injection. That study used photoactivated PRP as its treatment modality.[2]. [3] (See below for a more complete description of photoactivation.)

Some case series published have shown 50% or more pain relief after the first injection of cell therapy. One study from Iran reported on patients five years later after a single treatment. These patients, even after 8 years, were still in less pain and more functional than before the treatment. Their pain relief was not complete, but still significant after five years.[4]

  1. How many treatments will I need?

Some people heal completely after one treatment. Others – particularly those with badly damaged joints like arthritic deformed knees – may require up to 3 or 4 treatments. It depends on how healthy the damaged tissues are at the outset, and how willing you are to modify diet and lifestyle to allow for minimum inflammation and maximum healing.

Three treatments for a damaged arthritic knee joint is about the average.

  1. Are the additional treatments included in the cost of the first treatment?

Additional treatments cost somewhat less than the first one. The same follow-up visits are included with cost of treatment. The same healthy food choices are recommended and the same stem-cell building supplements.

Lifestyle change is crucial, for maximal healing and lasting benefit.

  1. Does stem cell therapy work only where it is injected?

You have probably read about surgical implantation of stem cells into the brain or spinal cord, into the pancreas or the lungs, in an effort to heal disease in these organs. An interesting paper written in 2014 by researchers at Tulane School of Medicine demonstrated convincingly that stem cells liberate their growth factors wherever they are injected, and can have an effect far distant from where they are initially injected. In this mouse study, stem cells were injected into the abdominal cavity to treat a mouse model of multiple sclerosis, and were found to be effective in reducing tissue damage and inflammation.[5] Stem cells are well known to home in to areas of acute injury, but the liberation of their growth factors affects the entire body. It seems like a pretty efficient way to help the body invoke what it normally produces for healing.[6]

  1. How do you decide which form of cell based therapy to use?

There are three forms of therapy which can be used. All have been proven effective under some circumstances. None has been shown to be 100% effective in all circumstances.

Platelet rich plasma, adipose-derived mesenchymal stem cell (MSC) and bone marrow are the three modalities most likely to yield lasting results.

How many of these therapies we use at one time depends upon the severity of the illness or injury, your physical condition, the extent of damage to the joint, and how much therapy you choose to do. The three forms of cell-based therapy are additive, and do not appear to interfere with each other. In the ideal world, we would use all three forms to maximize healing potential.

  1. What are platelets?

Platelets are tiny pieces of a cell in the bone marrow called a “megakaryocyte”. They are little bags of growth factors which encourage the formation of a clot. Their number can be measured, and the amount of clotting factors which appear in the blood can be measured. Platelets also produce many chemical messengers – small proteins, also known as peptides – which call stem cells to the area of injury to initiate the healing process.[7]

  1. How are platelets obtained?

Platelet Rich Plasma (PRP) is isolated from your own blood by a process called gradient density centrifugation. During this process about 60 cc (about 4 tablespoons) of blood is drawn from your vein and then centrifuged at low speed to separate the red cells from the clear serum. The platelets are found concentrated in a layer between the serum and the denser red cells. This layer, called PRP (platelet rich plasma) has been shown to contain many growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-ß), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin-like growth factor (IGF), etc. PRP has been successfully used in a variety of clinical applications for improving both bony and soft tissue healing.

  1. Is it possible to activate platelets without triggering clotting?

For orthopedic surgical procedures, platelet rich plasma is generally made to clot, using one of a number of different substances, so that the resulting “gel” will stick to the injured cartilage better.[8] The thinking is that when doing surgery on one joint, it is better to concentrate the growth factors in that joint, rather than diluting the platelet function throughout the body.3

For our purposes, since we want the platelets to stimulate growth factors not only locally but also throughout the body, the PRP is activated by exposing it to particular wavelengths of both visible and infrared light, in a process called Photoactivation.

  1. Why not use adipose tissue?

Adipose tissue has the highest concentration of mesenchymal stem cells of any tissue in the body, even higher than bone marrow. Adipose-derived stem cells also secrete higher amounts of healing growth factors (called cytokines).[9]

Adipose tissue is easily obtained through liposuction, generally from the abdomen where most of us have more tissue than we really want. The number of viable stem cells that can be collected does depend upon the type of procedure used for harvesting them.[10] These stem cells are also photoactivated so that their healing process can begin immediately, with minimal inflammation in the joint.

  1. How is liposuction performed safely?

Liposuction is done by injecting a small volume of anesthetic solution into the fatty tissues of the abdomen, and then removing around 4 tablespoons of fat for processing.

When performed properly, removing only small amounts of fatty tissue, liposuction is an extremely safe and surprisingly painless procedure.

  1. Why not use both platelets and adipose tissue?

Mesenchymal adipose-derived stem cells release extracellular vesicles. Treatment with platelets stimulates the release of extracellular vesicles, changes their protein composition and triggers the formation of blood vessels – the initial step of wound healing. Platelet-rich plasma has also been shown to enhance the proliferation and overall healing potential of human adipose-derived stem cells.[11],[12]

Using both PRP and MSC together seems like a win-win situation.

  1. How about using bone marrow?

For our purposes - using stem cell therapy to heal that which is not strong enough to heal on its own - we use bone marrow without any further manipulation. We simply filter it to remove any clumps or tiny bits of bone, activate the stem cells by photoactivation, and re-infuse it immediately into the patient’s blood stream or their unhealthy joint.

How well the bone marrow works depends on two factors – the patient’s overall state of health and the number of stem cells that are injected. We use a very special bone marrow harvesting needle which allows us to harvest only bone marrow, without diluting it with peripheral blood as happens using a standard bone marrow harvesting needle. We withdraw about 10 cc (2 teaspoons) of blood from the bone marrow.

  1. Why use platelets instead of bone marrow or adipose tissue?

Platelets contain significant amounts of key growth factors, like PDGF-AB (platelet-derived growth factor AB), TGFb-1 (transforming growth factor b-1) and VEGF (vascular endothelial growth factor), which are able to stimulate cell proliferation (meaning increase in numbers), matrix remodeling (meaning changing the composition of the fluid that surrounds and supports cell growth) and angiogenesis (meaning growth of new blood vessels, which the body uses like a supply line for repair of damaged tissues).

  1. Is stem cell therapy safe if I have had cancer?

Stem cells, in theory, can produce any type of cell within the body. We are coming to realize that cancer is such a difficult disease to treat because it is generated from its very own cancer stem cells which travel in advance of the wave of expanding partially differentiated tumor cells.

So why don’t our own normal stem cells turn into cancer cells? What keeps them in check?

We know that when we culture embryonic stem cells, they sometimes are unable to turn off their growth and division genes. When normal stem cells are cultured to increase their number artificially, sometimes the same thing happens.[13]

If cancer is already present in the body, there is evidence from a mouse study that normal stem cells can promote the growth and metastasis of tumors.[14]

Is it any surprise that injecting stem cells which produce growth factors, together with tumor cells, might cause tumor cells to grow? Mice do not have exactly the same metabolism and genetics as humans, but if something harms a mouse, I would be reluctant to use that same something on humans.

The real question is whether stem cells injected into a human being without known cancer will potentially cause an unknown or very small cancer to grow.

We do not do stem cell therapy with patients who have had a diagnosis of cancer. We do not KNOW that micrometastases will be activated, but we are unwilling to take the chance.

We will do PRP therapy for painful arthritic joints in patients who have had a history of cancer, as long as their currently painful joints are not due to the cancer disease process, and as long as the patients no longer have any evidence of active cancer in their bodies. It is very important that the patient understands the potential (albeit remote) risk of activation of cancer cells which are currently invisible to detection in their bodies.

We cannot guarantee perfect safety, only that we will do our best to avoid known potholes in the road of regenerative medicine.

If you are interested in exploring cell based therapy for your chronic painful joint or chronic illness, call us to speak with our new patient coordinator. She will schedule a free 15-minute phone consultation with one of our practitioners who will be happy to discuss the pros and cons of your particular case and to determine whether cell based therapy has a good chance of helping your condition.

[2] Freitag JB1, Barnard A. To evaluate the effect of combining photo-activation therapy with platelet-rich plasma injections for the novel treatment of osteoarthritis. BMJ Case Rep. 2013 Mar 26;2013. pii: bcr2012007463. doi: 10.1136/bcr-2012-007463.

[4] Davatchi F, Sadeghi Abdollahi B, Mohyeddin M, Nikbin B. Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three patients. Int J Rheum Dis. 2015 May 20. doi: 10.1111/1756-185X.12670.

[5] Semon JA, Maness C et al. Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis. Stem Cell Research & Therapy 2014, 5:2.

[6] Wasterlain AS, Braun HJ et al. The systemic effects of platelet-rich plasma injection. Am J Sports Med. 2013 Jan;41(1):186-93. doi: 10.1177/0363546512466383.

[8] Whitman DH, Berry RL, Green DM. (1997) Platelet gel: an autologous alternative to fibrin glue with applications in oral and maxillofacial surgery. J Oral Maxillofac Surg 1997; 55: 1294-1299.

[9] Melief SM, Zwaginga JJ et al. Adipose Tissue-Derived Multipotent Stromal Cells Have a Higher Immunomodulatory Capacity Than Their Bone Marrow-Derived Counterparts. Stem Cells Trans Med June 2013 vol. 2 no. 6 455-463. doi: 10.5966/sctm.2012-0184.

[11] Kakudo N, Minakata T, Mitsui T, Kushida S, Notodihardjo FZ, Kusumoto K. (2008) Proliferation-promoting effect of platelet-rich plasma on human adipose-derived stem cells and human dermal fibroblasts. Plast Reconstr Surg. Nov122(5):1352-60.

[12] Morikuni Tobita, Satoshi Tajima, Hiroshi Mizuno. Adipose tissue-derived mesenchymal stem cells and platelet-rich plasma: stem cell transplantation methods that enhance stemness. Stem Cell Research & Therapy 2015, 6:215 doi:10.1186/s13287-015-0217-8.

[13] Borgonovo T, Solarewicz, MM et al. Emergence of clonal chromosomal alterations during the mesenchymal stromal cell cultivation. Molecular Cytogenetics20158:94. DOI: 10.1186/s13039-015-0197-5.

[14] Rowan BG, Gimble JM et al. Human adipose tissue-derived stromal/stem cells promote migration and early metastasis of triple negative breast cancer xenografts. PLoS One. 2014 Feb 28;9(2):e89595. doi: 10.1371/journal.pone.0089595.