Regenerative medicine is an advanced branch of translational research enabling the management of acute or chronic pain conditions. The research in tissue engineering and molecular biology creates an environment in which the regeneration of human cells is achieved to restore or establish normal physiological functioning. The science applies findings from tissue engineering that dates back to 1962 with the first synthetic skin used in grafting procedures. Regenerative medicine for pain is rapidly growing, offering benefits to individuals who suffer from a number of different medical conditions.

Regenerative Procedures

There are two major kinds of stem cells: embryonic and adult. Embryonic stem cells (ESCs) are present only during the earliest periods of human life development, around 5 days after the egg is fertilized. As a result they are obtained from embryos formed by eggs which have been fertilized in the lab and donated for research purposes.

Embryonic stem cells are pluripotent. This means that they can divide and develop into all types of specialized cell in the human body. Because of this ability, embryonic stem cells hold the most potential for regenerative medicine. However, the FDA limits their use due to ethical issues and scientific challenges like the potential for the transmission of genetic diseases, tissue rejection and controlling how they differentiate.


Adult stem cells appear as the fetus grows and remain present in the body for the rest of the person’s life. These stem cells are able to self-renew for many years and give rise to more adult stem cells. Adult stem cells are multipotent and tissue-specific. This means that they divide and develop only into the specialized cells of the tissues they live in. These adult stem cells are found in the bone marrow, fat tissue, skin, muscles and intestines. Adult stem cells include hematopoietic stem cells and mesenchymal stem cells.


Hematopoietic stem cells (HSCs) or blood forming stem cells give rise to many erythrocytes (red blood cells), leukocytes (white blood cells) and platelets every day. There are several types of hematopoietic stem cells and the most common is the hematopoietic stem cell (HSC-CD 34+). HSCs do not decrease in number as we age and they are responsible for tissue regeneration.


Mesenchymal stem cells (MSCs) which are also known as marrow stromal cells, are obtained from fat tissue and the bone marrow. MSCs have the ability to form osteoblasts (bone forming cells), chondrocytes (cartilage forming cells), myocytes (muscles forming cells) and adipocytes (fat cells). MSCs reduce in number as we age. Studies suggest that they have a vital role of prepping the microenvironment to ensure that the hematopoietic cells are better able to do their work.


Stem cells are contained within bone marrow.  This autologous (obtained from oneself) bone marrow aspirate contains not only mesenchymal stem cells (cells that are able to develop into the tissues such as bone and cartilage) and progenitor cells, which are a different type of stem-like cell.  Bone marrow also contains other cells that produce growth factors and cytokines (cells that affect the behavior of other cells).  These cytokines aid in fibroblastic proliferation. Fibroblasts are cells that synthesize the structural framework.  Stem cells have the ability to form tissues like bone, cartilage, labrum, meniscus, ligaments and more.


On the other hand adipose tissue is also a rich source of adult stem cells. These cells, harvested from one’s own fat, have an extensive proliferative capacity and can differentiate into multiple cell lines. Stem cells derived from adipose tissue can differentiate ligaments, bone, cartilage, muscle or ligaments. This type of stem cell is now being used in musculoskeletal medicine to regenerate not only the above tissues but to provide a scaffolding to hold the stem cells in place and allow them to grow.  Adipose derived stem cells are similar but not identical to bone marrow cells.

History

The procedures of Regenerative Medicine primarily include Prolotherapy, Platelet Rich Plasma  (PRP) injections and Stem Cell Therapy.




​Prolotherapy is an injection procedure used to treat connective tissue injuries of the musculoskeletal system that have not healed by either rest or other nonsurgical therapies in order to relieve back pain. The injections promote a healing response in small tears and weakened tissue, with the goal of alleviating back pain and improving function. Prolotherapy is also referred to as sclerosant therapy, sclerotherapy, regenerative injection therapy, "proliferative" injection therapy, and nonsurgical ligament reconstruction.


A theory behind prolotherapy is that back pain is related to activation of pain receptors in tendon or ligament tissues, which are sensitive to stretching, pressure, etc. It is thought that the cause of back pain is from ligamentous laxity. With the prolotherapy procedure, the substance injected into the soft tissue causes an inflammatory response at the site, which in turn causes natural healing to take place (formation or "proliferation" of new blood vessels), with the goal of strengthening the torn or injured soft tissue and reducing the back pain.

In prolotherapy treatment, often used for chronic back pain, a substance is injected using a slender needle next to the site where soft tissue (ligament, tendon, muscle, fascia, joint capsule) is injured or has torn away from the bone. The substance used in the prolotherapy injection is a natural irritant agent. Examples include:

Sugar (dextrose or glucose) alone or in combination with glycerin and phenol
Sodium morrhuate (a purified derivative of cod liver oil)

During prolotherapy treatments for chronic back pain or other disorders, the agent is typically used with a local anesthetic (lidocaine, procaine, or marcaine). Prolotherapy involves a series of injections, reportedly ranging from 3 to 30 (average 4 to 10), depending on the back condition and the individual being treated. The prolotherapy injection series may cover 3 to 6 months with injections at 2 to 3 week intervals.

Definition of Stem Cells

Prolotherapy

Stem cells are an undifferentiated cell from a multicellular organism. These cells are capable of developing into other specialized types of cells found within the body through differentiation, triggered by cellular programming. There are two different types of stem cells found in a developing organism and one that is genetically reprogrammed within the laboratory.

Embryonic stem cells are the most immature and are found within the early stages of a growing embryo, usually after it has been left to develop five to six days. After the egg and sperm have united, the fertilized egg divides and creates stem cells that differentiate into the specialized cells the body requires to function.

The second type of stem cell, found naturally in organisms, is adult stem cells. These are present in developed tissue, such as muscle, skin, bone, brain, and blood. Also called tissue stem cells, they can self-renew and generate one specialized cell type. Under normal circumstances these tissue stem cells, or adult stem cells, will generate the type of cells that make up the organ in which they reside. These cells are used by the body to divide and repair injured areas or regenerate into specialized cells to replace the ones that are dead or damaged.

The third type of stem cells, which are genetically reprogrammed in the laboratory, are induced pluripotent stem cells. After years of stem cell research and development, it was discovered that artificially triggering certain genetic components would prompt different cells to become pluripotent stem cells, which were similar in nature to embryonic stem cells, thus avoiding ethical concerns associated with using human embryonic tissue for research and regenerative medicine.

Although first used in the 1970s, platelet-rich plasma therapy was limited to operating room procedures because the equipment was large and expensive and the procedure required large quantities of the patient’s blood. Today it is used to target a number of different conditions in which the patient develops chronic pain. The procedure requires an injection of autologous growth factors, secretory proteins, and concentrated platelets. These compounds work in unison to repair damaged tissue and speed the healing of surgical procedures.


The injection of platelet-rich plasma to an injured area delivers growth factors concentrated from five to ten times greater than is normally found in plasma. The compound is prepared through withdrawal of blood from the patient, centrifugation to increase the concentration, and then injected into the area that was damaged or injured. When the blood is centrifuged, it separates into three different components. The top layer is clear serum, platelets and white blood cells are found in the middle, and the red blood cells are at the bottom.


Platelets contain a high concentration of growth factor, which is central to the function of platelet-rich plasma therapy in regenerative medicine for pain management. Once injected into the damaged area, the platelets release other proteins that are believed to affect the regenerative influence patients experience after treatment. This process enhances the differentiation of cells, which is believed to be the underlying process required for the generation of new tissue. As with stem cell therapy, most patients report only some soreness at the injection site that may or may not be accompanied by bruising.


The patient is usually seen in an outpatient clinic and able to undergo the procedure without general anesthesia. Regenerative medicine treatment protocols are done on an outpatient basis and require little to no recovery period. Oftentimes individuals are able to return to work directly following the procedure.The majority of the time, regenerative medicine involves using the patient’s own stem cells and other supporting cells. The harvested material is concentrated, purified, and injected into the damaged area where the expected results include regeneration and repair of damaged tissue.

Stem Cells Types

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Platelet Rich Plasma (PRP)