September 8

Types of Regenerative Medicine

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From the first time I heard about “stem cells,” I was fascinated.  Unfortunately, as is often the case in medicine, the research didn’t fulfill the theoretical promise…until recently.  It seems as if almost everything we thought we understood about including stem cell therapy and the way it works has changed in the last 3-5 years.  And those changes in our understanding have brought the theoretical possibilities and the research results closer than ever.

My interest in stem cell therapy prompted me to obtain a Masters of Science degree in Public Health, with a concentration in Epidemiology, in 2011.  Epidemiology involves the study of organisms (bacteria, viruses, fungi, prions, etc.), their transmission, distribution, impact on the human body, and more.  Armed with this additional education, I understood that stem cell therapy hadn’t reached its full potential, and I hesitated to recommend it to my patients back then.  Over a year ago, I turned my attention to the field once more, after dozens of inquiries by my patients.  I was thrilled to see that stem cell therapy and other types of Regenerative Medicine had taken an exponential leap forward.  Finally, I’m confident to recommend stem cell therapy and Regenerative Cellular Therapies (RCT) to my patients in St. Petersburg, FL.

What is Regenerative Medicine?

Regenerative Medicine is a form of molecular biology which deals with the “process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function.” When injured or ill, our bodies have the built-in ability to heal and defend. Harnessing and enhancing the body’s innate regenerative powers is a medical field at the forefront of scientific advancements whose properties may seem miraculous to those who benefit from them.

How Does Regenerative Medicine Work?

Cells are the building blocks of tissue.  Tissues are the basic unit of function in the body and combine to make our organs and our systems. Generally, groups of cells make and secrete their own support structures, called the extracellular matrix. This extracellular matrix (ECM), or scaffold, physically supports the cells and acts as a relay station for molecular signals. The ECM enables cells to receive messages from a variety of local sources. Each signal can initiate a series of responses that determine what happens to the cell. Through scientific advancements we can now understand how individual cells respond to signals, interact with their environment and organize themselves into a healing process. Scaffolds can be created or enhanced utilizing various types of Regenerative Medicine therapies.

Types of Regenerative Medicine Therapies

For a broad overview of available Regenerative Medicine therapies, see the outline below.  Each option will be discussed in more detail in its own section.

  1. Platelet-Rich Plasma (PRP)
  2. Stem Cells
    • Autologous
      • Adipose-derived
      • Bone Marrow Aspirate Concentrate (BMAC)
    • Allogeneic
      • Embryonic
      • Placental
      • Cord Blood
      • Wharton’s Jelly
  1. Amniotic Fluid
  2. Exosomes
  3. Regenerative Cellular Therapy Comparison Table

Platelet-Rich Plasma (PRP)

Often misrepresented as stem cell therapy, PRP is created by drawing blood from a patient’s vein into a test tube containing an anticoagulant.  The tube is then placed into a centrifuge to “spin down.” Since red blood cells contain iron, they’re heavy and sink to the bottom of the test tube.  The next layer up (on top of the red blood cells in the tube) is a thin whitish-brownish layer called the “buffy coat.”  The buffy coat contains white blood cells and platelets.  The final layer at the top of the test tube contains a yellowish liquid called plasma. Plasma is made up of water, proteins, hormones, glucose, electrolytes, and oxygen.  It’s rich in growth factors and other substances that “kick-start” our immune system. The medical professional draws the plasma out of the centrifuged test tube and into a syringe.  The PRP is then ready to be injected into the problem area.

Platelets are generally known for their ability to clot blood, but they also contain proteins known as growth factors that play a critical role in the healing process. Since the location of many musculoskeletal injuries doesn’t have a good blood supply, the areas and injuries don’t receive adequate platelets and growth factors to repair and regenerate damaged tissue. PRP delivers these vital ingredients directly to the location in crisis to facilitate healing.

Additionally, PRP activates cells called tenocytes to proliferate quickly and produce collagen to repair tissue. PRP is said to begin working in hours or days but, alone, can take 6-9 months to reach its full effect. However, PRP in conjunction with other types of Regenerative Medicine products may accelerate the healing process and reduce healing time by as much as eighty percent.

Stem Cells

In simple terms, stem cells are undifferentiated, or “blank,” cells. What this means is they’re capable of developing into cells that serve various functions in different parts of the body.

In contrast, differentiated cells can only serve a specific purpose in a specific organ. Most cells in the body are differentiated cells. For example, red blood cells are specifically designed to carry oxygen through the blood.

Undifferentiated cells have the ability to divide and make an indefinite number of copies of themselves. Other cells in the body can only replicate a limited number of times before they begin to break down. When a stem cell divides, it can either remain a stem cell or turn into a differentiated cell, such as a muscle cell or a red blood cell.

While a stem cell can, by definition, turn into other cell types that a body may need, that is not where their true magic lies.  Think of a stem cell-like the conductor in an orchestra, who is able to signal and communicate to help everyone around him or her to do their jobs better.  The conductor takes individual pieces and sounds and turns them into a symphony.  Similarly, the power behind stem cells is found in their ability to signal to and communicate with the cells around them, causing those cells to do their jobs, better.  (They do this by using exosomes – more on this in a little bit!)

Types of Stem Cells

There are multiple ways to categorize stem cells, but perhaps the easiest way is to classify those stem cells that come from our own body (“autologous”), and those stem cells that are donated by other people (“allogeneic”).

Autologous Stem Cells: Adipose-Derived

The first type of autologous stem cells is Adipose-Derived.  Adipose (fat) contains Mesenchymal Stem Cells (MSCs). According to a 2015 research article by

adipose suction imageAdipose (fat) is collected from the patient via mini-liposuction. This procedure should be performed by a licensed physician in a hospital setting under light general anesthesia as it can be painful. The physician will determine the most appropriate location(s) to perform the incision(s) for the required fat tissue extraction. (Picture available at: https://doi.org/10.1016/j.eats.2017.06.048)

While recovering, your stem cells will be separated from your fat tissue and the doctor will then inject those cells (just like getting a shot or an IV) back into your body. The entire procedure normally takes four to five hours and the number of viable cells obtained is greatly dependent on the age of the patient.

As we age, our numbers of stem cells drop dramatically, and their ability to divide as well as to secrete bioactive substances declines precipitously.  For example, 1 in every 10,000 cells in a newborn is a stem-cell, compared to 1 in 2,000,000 cells once you’re 80 years old.  By the time we’re 18-20, we’ve used up 90% of our available stem cells.

One advantage of adipose-derived stem cells is that your body will not reject them because they come from you.  However, the cons likely outweigh the pros.  Your stem cells are the same age as you are, and they may not significantly help you once you’re over the age of 30-40.  The procedure is painful and invasive.  It takes more time and costs more money because it has to be performed in a hospital setting.

Autologous Stem Cells: Bone-Marrow Aspirate Concentrate (BMAC)

The second type of autologous stem cell is Bone Marrow Aspirate Concentrate, or BMAC.  The BMAC procedure yields Hematopoietic Stem Cells.  According to the National Cancer Institute, these are: “An immature cell that can develop into all types of blood cells, including white blood cells, red blood cells, and platelets. Hematopoietic stem cells are found in the peripheral blood and the bone marrow.” 

In this procedure, a large needle is used to extract bone marrow from the center of the bone. This is usually done under sedation or general anesthesia. Marrow is commonly taken from the pelvis but may be taken from other sites. The pelvis is marked and prepped to keep the site sterile. A hollow needle is inserted into the bone and a syringe is used to withdraw fluid from the bone marrow.

After enough fluid has been collected, the needle is removed, although it may take several punctures to obtain enough marrow. After the procedure, it may take several days or weeks for the extraction site pain to completely resolve.

The extracted bone marrow is then spun down in a centrifuge to separate the cells. A liquid is produced that has a high concentration of stem cells. The physician injects the stem cells directly into the injured site. This method is avoided in patients who have an infection or cancer. Complications may include pain, bleeding, infection, anesthesia-reaction, and nerve injury. An intra-abdominal injury may occur because of the needle.

 

Bone Marrow Aspirate ConcentrateWhile a BMAC may be the only available option for some patients, it’s not necessarily the best option due to the complications mentioned above.  In addition, the BMAC procedure is more expensive.  As with adipose-derived treatments, the stem cells harvested in a BMAC procedure are the same age as the patient and may not be as potent and vibrant as a young stem cell.

Allogeneic Stem Cells

The second broad category of stem cells are allogeneic stem cells.  These are harvested from screened, healthy, donated birth tissues.

Allogeneic Stem Cells: Embryonic

Most embryonic stem cells are derived from embryos that develop from eggs fertilized in a fertility clinic.  Once the donors no longer need the fertilized eggs, they can be donated for research purposes with the informed consent of the donors. They are not derived from eggs fertilized in utero, or from aborted fetuses.

Stem cells found in embryos robustly divide because their job is to make a baby from two cells.  In research and clinical application, they have been found to be tumorigenic, meaning that they can cause the creation of tumors.  In hindsight, it makes sense that these cells are trying to form a baby no matter where they are placed.  As a result, most research and clinical use involving embryonic stem cells ceased in the 1980s and 1990s.

Allogeneic Stem Cells: Non-Embryonic

Non-embryonic sources of stem cells include the placenta, amniotic fluid, cord blood, and Wharton’s Jelly.  Each will be discussed below, but first, let’s talk about how these tissues are obtained.

Birth tissue is donated by healthy mothers at the time of a scheduled cesarean section. Expectant mothers submit their past medical and social history, which is prescreened through an extensive and comprehensive review and pre-natal evaluation. This process is performed prior to delivery utilizing the protocols established by various regulatory agencies. Additionally, prior to delivery, the mother is tested for communicable diseases following the requirements of the Food and Drug Administration (FDA), Center for Disease Control (CDC), and the American Association of Tissue Banks (AATB).

The recovery of the birth tissues is performed by specially trained technicians at the time of the delivery. Since the discovery of birth tissue as a viable cellular matrix in 2005, there have been no reports of adverse events or disease transmission. Additionally, birth tissue is considered immune-privileged and as such does not express Class II antigens (your body cannot reject them).

Allogeneic Stem Cells: Placental

The placenta and umbilical cord have been found to be sources of hematopoietic stem cells – these are cells that can turn into red blood cells and various types of white blood cells.

Allogeneic Stem Cells: Amniotic Fluid

Just as the amnion (innermost layer of the placenta) protects the fetus during development, it can also provide the same protection to injured or traumatized tissue. Amnion contains collagen substrates, a full range of growth factors, amino acids, carbohydrates, cytokines, hyaluronic acid, fibroblasts, epithelial cells and extracellular matrix. It has anti-inflammatory properties and is considered to be immune-privileged.  However, it contains fewer MSCs than other birth tissues. 

Allogeneic Stem Cells: Umbilical Cord Blood 

Umbilical cord blood is blood that remains in the placenta and in the attached umbilical

cord after childbirth. Umbilical cord blood contains mesenchymal stem cells, which can be used to treat hematopoietic and genetic disorders. These stem cells have the capacity to propagate, release growth factors and cytokines, as well as differentiate into more mature cells. Additionally, due to the immune-privileged nature of umbilical cord cells, there is a significantly decreased risk of “graft-versus-host disease” (GvHD) or rejection reaction, and if GvHD does occur it is less severe than most other types of transplants.

Allogeneic Stem Cells: Wharton’s Jelly

Wharton’s Jelly was first described in 1656 and is the tissue surrounding the umbilical vein and vessels in the umbilical cord. Derived from the fetal side of the umbilical cord, this tissue contains up to 50 times more MSCs, growth factors and other components than the amniotic fluid, making it the richest source of MSCs we’re currently aware of. Wharton’s Jelly products are especially beneficial for patients over forty that, due to the aging process, have less viable cells than a younger patient would have.

Wharton’s Jelly is rich in collagen,  hyaluronic acid which cushions and lubricates joints, chondroitin sulfate which is found in cartilage, and telomerase.  Telomerase helps the body replace telomeres – end caps on the DNA that shorten each time a cell divides by mitosis.  Without telomerase, a cell would only be able to divide 50-70 times before the telomere would be too short and division would cease. By maintaining and replacing telomeres, cells are able to divide more.  Therefore, the length of the telomeres is correlated to the lifespan of the cell, or the organism.

Exosomes

As we discussed earlier, the power of a stem cell is found in its ability to signal and communicate with all of the other cells around it, like the conductor in an orchestra.  Stem cells are able to communicate with the cells around them by using exosomes.  Exosomes were initially discovered over 30 years ago but were erroneously thought to be “garbage cans” to remove waste materials from cells.  We now know their role is to communicate with other cells to alter function and physiology.

Exosomes can be described as little packets of bio-active substances.  The substances are created inside the stem cell (think of it like a tiny factory, capable of producing over 300 bio-active substances when young and vibrant), then packaged in a lipid (fat)-coated packet.  The lipid-coating enables the exosomes to pass through the stem cell’s cell wall, across space between cells, and through the cell wall of the recipient cell.  The recipient cell can then open the exosome, and use the materials inside to heal, repair, and regenerate.  Stem cells can even donate mitochondria (tiny organelles that make cellular energy) to distressed or damaged cells in this fashion!

Exosome therapy is on the cutting-edge of the Regenerative Medicine field.  We are just beginning to discover its power and potential.  At Thrive! Wellness Center, we combine MSCs (the factories) with exosomes (the building materials) to produce optimal clinical results.

 

Optimal Results Treatment Model

At Thrive! Wellness Center, we believe in doing everything we can to help our patients have the best possible clinical outcome.  It starts with a thorough intake and history process where we review medical records and prior imaging.  Next, we perform a comprehensive examination of the area in distress.  This may involve orthopedic tests, neurologic tests, range of motion, palpation, and imaging.  Our medical team reviews the case and determines what types of Regenerative Medicine therapies (if any) are appropriate.  The basis of our treatment is this belief: Repair & regeneration of biological tissue is superior to replacement with mechanical / artificial components.

In musculoskeletal issues, we often take a 4-pronged approach to treatment.  First, we increase cellular energy with Deep Tissue Laser Therapy.  Next, we lay the foundation of regeneration with PRP to reduce inflammation, remove waste, and provide a matrix to prepare the site for healing.  On the second treatment, we use Deep Tissue Laser Therapy, followed by an injection of MSCs and exosomes into the injured area.  The third and fourth treatments involve Deep Tissue Laser Therapy to increase cellular energy, and PRP to continue to provide raw materials for building, repair, and regeneration.  We may also incorporate IV nutritional therapy to maximize results.

In addition to using Regenerative Medicine for relief of degenerative and/or painful conditions, we also use these therapies for aesthetics/anti-aging, hair regrowth, wound healing, and sexual rejuvenation.

In musculoskeletal issues, we often take a 4-pronged approach to treatment.  First, we increase cellular energy with Deep Tissue Laser Therapy.  Next, we lay the foundation of regeneration with PRP to reduce inflammation, remove waste, and provide a matrix to prepare the site for healing.  On the second treatment, we use Deep Tissue Laser Therapy, followed by an injection of MSCs and exosomes into the injured area.  The third and fourth treatments involve Deep Tissue Laser Therapy to increase cellular energy, and PRP to continue to provide raw materials for building, repair, and regeneration.  We may also incorporate IV nutritional therapy to maximize results.

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cellular therapy, prp injections, prp therapy, regenerative medicine, stem cell therapy


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