What is Regenerative Medicine?
Regenerative Medicine Explained by Las Vegas, Summerlin, and Henderson Nevada’s Top Pain Doctors
Regenerative medicine is a rapidly evolving, advanced technology in the management of many acute and chronic pain conditions. Chronic pain is a common condition that can cause numerous detrimental impacts on an individual’s ability to function on a day-to-day basis. Musculoskeletal pain, specifically, has historically been regarded as the number one cause of chronic disability in the United States. Further, chronic musculoskeletal pain has also been found to be the leading contributing factor to higher rates of physician appointments. Across both acute and chronic conditions, prevalence rates have estimated that approximately 100 million adults experience difficulties with regard to back pain every year. Regenerative medicine has not been approved to treat all cases of pain; however, depending on the individual’s specific pain condition, regenerative medicine may be considered as an appropriate and effective treatment.
Drawing from research in the areas of biology, chemistry, computer science, engineering, genetics, medicine, and robotics, regenerative medicine involves the construction of biological substitutes for many of the tissues found in the body. The general idea behind regenerative medicine, or tissue engineering, is drawing from the work of science and technology so that researchers are able develop biological substitutes, which will act to restore, maintain, and improve the functioning of damaged or lost tissue.
Regenerative medicine is a relatively new procedure, though its origins date back as early as 1962, when the first synthetic skin substitute was used. While there are many misconceptions maintained regarding regenerative medicine, advances in technology have allowed for the development of new procedures for treating many common orthopedic conditions, which do not require an operation. In fact, many of the regenerative medicine interventions are minimally invasive. The common orthopedic conditions that have been successfully treated through the use of regenerative medicine procedures include arthritis, as well as injuries to the body’s cartilage, spinal discs, bone, tendons, ligaments, muscle, or other bodily tissue.
History of Regenerative Medicine for Pain
Regenerative medicine is believed to have originally emerged from a number of scientific and technological advances that span a diverse spectrum of fields. Also known as tissue engineering, regenerative medicine utilizes existing living tissue cells and biocompatible materials, along with both biochemical (such as growth factors found in the body) and physical factors to generate tissue-like constructs that may be used to repair tissue that has been damaged as the result of an injury or to replace an organ failing as the result of normal aging.
Tissue-based procedures related to regenerative medicine originated from early techniques in skin grafting. Originally developed in 1962, the first successful tissue-engineered procedures were performed in the 1970s. Beginning by harvesting a skin biopsy, Howard Green and his colleagues at Harvard Medical School perfected techniques in growing skin epidermis. This technology has also historically been applied clinically to help individuals with other conditions. Since the 1960s, regenerative therapy has drawn from stem cell technology to provide bone marrow transplants to help individuals suffering from leukemia.
Basis of Stem Cell Technology in Regenerative Medicine
Stem cells are undifferentiated cells that carry with them the potential to develop into any one of the broad range of specialized cells found within the body. At the very basic level, there are two types of stem cells that can be found in a developing organism: embryonic stem cells and adult stem cells. Embryonic stem cells are the most immature form of stem cells, and comprise the embryo. After an egg is fertilized, it begins to divide and create stem cells, which will eventually differentiate into all of the types of cells found in the body. While it is a bit of a misnomer, as adult stem cells are not only present in adults, they do exist within already developed tissue. They are found within the brain, blood, muscle, skin, and bone. Adult stem cells are responsible for repairs within the tissue making up the body. By residing within the already developed tissue, stem cells are able to divide often in order to continually regenerate newly formed specialized cells. These newly formed cells generally replace those that are dead or lost.
|Important Dates in the History of Regenerative Medicine|
|3000 BC||Descriptions of skin grafting were found in Sanskrit texts of India|
|1874||Scientists in Europe perfected the autologous skin grafting technique|
|1881||First cadaveric skin allograft|
|1944||The development of refrigerated skin allografts|
|1949||Cell cryopreservation at subzero temperatures was developed|
|1952||Skin cryopreservation was developed|
|1962||The Ivalon sponge was developed as an artificial skin|
|1975||In vitro cultivation of keratinocytes|
|1979||Later commercialized as Epicel, cultured autologous epithelium was developed|
|1982||Later commercialized as Dermal Regeneration Template, the collagen-glycosaminoglycans (CAG) – based dermal matrix was developed|
|1987||The term “tissue engineering” was coined|
|1988||Cell transplantation procedures were perfected in synthetic biodegradable polymers|
|1994||Later commercialized as Carticel, chondrocyte culture and transplantation was performed|
|2006||The first bioartificial bladder was cultured in vitro and implanted in vivo|
|2008||The first bioengineered trachea was produced from decellularized matrix seeded with human cells, which were obtained from stem cells|
For a number of years, scientists have been interested in stem cells because of their regenerative properties, as well as their ability to develop into any type of tissue that is found within the body. It is for these reasons that stem cells contain the potential for what is believed to be limitless clinical applications in the health care field. In fact, stem cell research is advancing the treatment options available as well as improving treatment outcome rates for diseases, such as Parkinson’s disease, Type I diabetes, heart disease, Duchene’s muscular dystrophy, Alzheimer’s disease, stroke, osteoarthritis, rheumatoid arthritis, and vision and hearing loss. This technology has also been utilized in the treatment of injuries, such as spinal cord injuries and severe burns. There are many scientists and researchers who firmly maintain the hope that in the future stem cell technology will lead to the possibility of repairing and replacing damaged or diseased tissue.
Indeed, the first tissue to be bioengineered was the skin. Following this, scientists were also able to successfully bioengineer cartilage. Both of these products, which were produced through tissue engineering, are available commercially to health care providers today. While these products arose on the market quickly and inspired enthusiasm for the possibility of generating all of the types of tissue that make up the human body through the use of tissue engineering, there are a number of problems that have prevented this progress. For example, both skin tissue and cartilage tissue do not require extensive vascularization, as other types of tissue do. This means that the generating process to engineer the tissue of both skin and cartilage can be completed using more simplified techniques, such as merely combining cells together.
Principals of Regenerative Medicine for Pain
Driven particularly by the discoveries of the body’s own ability to organize itself and regenerate tissue following cell death or loss, the primary goal of regenerative medicine, or tissue engineering, for pain, is to generate new tissue to replace tissue that has been injured, diseased, or is degenerating owing to advancing age.
Given that regenerative medicine involves the use of living cells, however, there are a number of ethical and legal issues surrounding the use of platelet-rich plasma and particularly that of embryonic stem cells. Of utmost importance in regenerative medicine is mimicking the environment from which the stem cells were drawn. While the FDA does not currently maintain any approval requirements with regard to adult stem cells, stem cell therapy does not currently have FDA approval. Moreover, physicians frequently go “off label,” when prescribing patients a form of treatment. This essentially means that the physician believes another type of drug, which has not undergone any clinical trials for that specific diagnosis, would greatly benefit the patient.
Types of Procedures Used With Regenerative Medicine
Of utmost importance in regenerative medicine is mimicking the environment from which the stem cells were drawn. This will allow the engineered cells to function as if they are still in their native tissue. In terms of musculoskeletal chronic pain, there are generally three types of regenerative medicine. These include the following.
Stem Cell Therapy
One type of regenerative medicine is stem cell therapy. This procedure is believed to be ideal for patients experiencing low back or neck pain owing to a degeneration of the vertebral discs or joint pain owing to osteoarthritis, such as that in the knees, hips, or shoulders. Through cell division, stem cells are naturally able to renew themselves and to differentiate, or specialize, into a wide range of different types of tissue found within the body. As such, stem cells can also be found at many sites within the body, including human embryos, skin cells, bone marrow, peripheral blood, placental blood, placental tissue, and adipose tissue. There are two general types of stem cells found within the body, which include embryonic stem cells and adult stem cells.
Beginning in the 1960s, stem cell technology was used to effectively treat individuals needing bone marrow transplants, such as individuals suffering from leukemia. Currently, stem cell technology is regarded as an interventional procedure for the treatment of a number of chronic pain conditions. Generally, this procedure involves extracting the patient’s own stem cells and other supporting cells from one of the known sites for stem cells. This material is then purified, concentrated, and injected into the damaged tissue. It is important that this concentration is not altered in any way.
The procedure for stem cell therapy is generally non-surgical and there is very little recovery time. Thus, stem cell therapy can potentially help patients avoid surgery and the potential side effects that are associated with it. Most patients report some soreness at the site of the stem cell injection, which may or may not be accompanied by bruising. There have been no reports of serious side effects following stem cell therapy.
Another type of regenerative medicine for the treatment of chronic pain is amniotic membrane therapy. The human amniotic membrane is comprised of several unique properties that make it ideal for use in regenerative medicine. The amniotic membrane is composed of two types of cells: epithelial cells and stromal cells. Both the epithelial cells and the stromal cells exhibit characteristics that are similar to stem cells in that they are able to differentiate in vivo. Previous literature examining animal models on the use of amniotic membrane following a minimally invasive surgical procedure called a laminectomy has shown the amniotic membrane’s effectiveness in reducing epidural fibrosis and scar adhesion. Studies examining the use of the amniotic membrane in human models provide some evidence for its effectiveness. In particular, amniotic membrane use has been supported as an efficacious treatment for general tissue damage, such as tendonitis.
Similar to that of stem cells, the procedure for using amniotic membrane as an interventional therapy for the treatment of chronic pain conditions is generally non-surgical and there is very little recovery time. Thus, amniotic membrane procedures can provide the benefit of not undergoing surgery. This allows many patients to avoid going on disability or be subjected to the other side effects that can often occur following major surgery. Amniotic membrane therapy involves injecting a concentrated compound of the patient’s own amniotic membrane to the site of the injury. Most patients report some soreness at the site of the injection, which may or may not be accompanied by bruising.
Platelet-Rich Plasma Therapy
Platelet-rich plasma therapy is utilized to target a number of different chronic pain conditions. First used in the 1970s, the platelet-rich plasma procedure involves injecting a concentrated compound of platelets, autologous growth factors, and secretory proteins, all of which act in concert to help repair damaged tissue at the site of the injury. In addition to pain management, the platelet-rich plasma procedure is widely used across the specialty areas of orthopedic surgery, plastic surgery, sports medicine, and wound care.
The concentrated compound used in the platelet-rich plasma technique is created from a sample of blood from the patient. This blood is centrifuged to separate the almost-clear fluid called the serum (which is found as the top layer), the platelets and white blood cells (found in the middle), and the red blood cells (found at the bottom). Estimates have suggested that the middle layer is comprised of a platelet concentration of around one million platelets/uL. A typical platelet concentration would fall somewhere between 150,000-350,000 platelets/uL. Further, this fluid also contains highly concentrated (up to three to five times greater) growth factor. This concentrated compound is then injected into the site of the injury, where the platelets synthesize and release other active proteins. These actions are believed to account for the regenerative effect that platelet-rich plasma therapy has on damaged tissue. More specifically, the synthesizing of platelets and the release of proteins enhances the recruitment, proliferation, and differentiation of cells, which are the underlying processes in generating new tissue at the cellular level. Most patients report only some soreness at the site of the injection following the procedure, which may or may not be accompanied by bruising.
Platelet-rich plasma therapy has received an extensive amount of attention within the literature. In fact, platelet-rich plasma therapy has been shown to have beneficial effects on the expression of genes and matrix synthesis within tendons. Furthermore, platelet-rich plasma therapy is linked with the proliferation of cells and increases in total collagen production. Results from studies examining the effectiveness of platelet-rich plasma treatment have provided support for its benefits in treating lateral epicondylitis, patellar tendinopathy, Achilles tendinopathy, rotator cuff tendinopathy, rotator cuff tears, medial collateral ligament and anterior cruciate ligament tears, and osteoarthritis. Platelet-rich plasma therapy is also used to treat other acute and chronic pain conditions including tendonosis, muscle strain, muscle fibrosis, arthritis, arthrofibrosis, articular cartilage defects, meniscal injury, and chronic synovitis or joint inflammation. Given that platelet-rich plasma therapy for chronic pain is non-surgical, there is very little recovery time and very few risks.
Types of Pain Conditions Treated With Regenerative Medicine
Patients who are interested in whether or not regenerative medicine is an appropriate treatment option for providing relief for their pain condition are encouraged to seek out a consultation with a physician that is an expert in the area of regenerative medicine. This consultation will likely include an in-depth medical evaluation regarding the individual’s underlying condition, and the potential for using regenerative medicine to treat the condition. This consultation will also include guidance from the expert physician regarding the procedures involved in regenerative medicine and what to expect. Indeed, many individuals hold misconceptions regarding the use and application of regenerative stem cell therapy; therefore, the consultation appointment serves to provide the patient with education regarding the process and to address any of the patient’s questions or concerns.
There are a number of pain conditions, including musculoskeletal conditions that are expected to benefit from regenerative medicine. During the initial consult with an expert physician in the area of regenerative medicine, your doctor will give you a medical evaluation consisting of a brief yet detailed personal history. The goal of this is to ensure an accurate diagnosis of the source of the pain, in order to determine the most appropriate regenerative medicine procedure. Indeed, in some cases of chronic pain, the precise cause is not identified. In these instances, the physician will want to ensure that certain diagnoses are ruled out. Your physician will also generally assess for your degree of risk for persistent difficulties.
Chronic pain can arise from a number of sources and many cases of chronic pain can originate because of a degenerative process or pathology. Damage to muscles, joints, or ligaments that comprise the spinal region can also be the main source of both acute and chronic pain. In general, back and neck pain is characterized by sensations of pain and discomfort that arises in the back and may radiate out toward the limbs. The specific symptoms or sensations of pain are widely varied. Some patients will experience the pain as a highly specific sharp stab, while others will describe the pain as more generalized and widespread. Further, the symptoms of chronic pain are expected to fluctuate over time. For instance, often dependent on environmental circumstances, a patient may fluctuate in and out of recurring symptoms and exacerbations of pain.
While the specific symptom clusters generally depend on the underlying cause, some common complaints include:
- Muscle spasms
- Radiating pain
- Tingling, numbness, or weakness
- Sensitivity to touch or pressure
Pain experienced within the body is thought to provide a strong indication that there is likely tissue damage or an underlying injury. In general, a number of treatments available for these common conditions merely help the patient cope with the debilitating pain, rather than addressing the underlying injury. New technology in the field of regenerative medicine has provided advancements in the types of treatments available for chronic pain. Indeed, these forms of treatment target the underlying problem, by promoting the body to heal itself through the use of stem cells.
Patients who suffer from the following list of conditions are potential candidates for regenerative medicine procedures.
Osteoarthritis is considered a chronic degenerative joint condition that is associated with extensive cartilage degeneration. This damage can be the result of wear and tear across a number of years or as the result of a specific injury. If the cartilage sustains enough damage, there is a high risk of bone rubbing directly onto bone. While there are a number of treatment options available for managing the pain of osteoarthritis, there is no cure for this condition. Indeed, stem cell therapy is believed to be more appropriate, as the goal of the therapy is to repair and improve the existing tissue.
Spondylolisthesis refers to the degenerative process of the individual bones of the spine, called the vertebrae. Most commonly caused by degenerative disc disease, spondylolisthesis is a condition that occurs when the vertebra becomes dislocated and “slips” over another. It is often referred to under nonspecific low back pain, because a large portion of patients with this anatomical deformity do not present with any related symptoms, including pain. During spondylolysis, the nerves around the weakened and slipped vertebrae can become compressed. Annual prevalence rates of within the general population estimate that approximately 12% of the population have had difficulties with regard to this condition.
Spinal stenosis is a common condition characterized by a restriction of the spinal canal, which is caused by a narrowing of the spinal column. The characteristic feature of spinal stenosis is neurogenic claudication, which is an inflammation of the nerves fanning out from the spinal cord. People with spinal stenosis often experience pain while walking. It is generally recommended that patients attempt more conservative forms of treatment prior to beginning regenerative medicine intervention.
These are genetically linked problems that relate to the curvature of the spine (e.g., scoliosis or kyphosis), and generally involve the entire spine. These difficulties are relatively uncommon. Recent prevalence rates are not available; however, early estimates suggest that spinal deformities occur in about 0.8% to 1.9% of the general population.
There is a higher prevalence of compression fractures among post-menopausal women with osteoporosis and in those who have had long-term corticosteroid use. One study, examining 7,000 women over the age of 65, found that 5% had sustained a compression fracture of a vertebra over the course of a four year period. Previous evidence suggests that approximately 4% of adults seen in primary care settings can attribute their symptoms of back pain to a compression fracture.
Degenerative disc disease
Degenerative disc disease is a condition related to the changes that occur within the intervertebral discs as people age. This aging of the intervertebral disc can cause tears, which is believed to be the source of the pain associated with degenerative disc disease. The pain associated with this particular disease can occur throughout the spine, however in some instances, the pain was reported to be localized to the affected intervertebral disc. Previous treatments for degenerative disc disease have generally been limited to physical therapy, over-the-counter or prescription pain medications, steroid injections, and spinal fusion surgery. New advances in technology have lead to the use of stem cell therapy for the treatment of degenerative disc disease. This involves extracting the patient’s own stem cells. This is typically done from the patient’s hip, as it is the ideal location for obtaining bone marrow. This marrow is then concentrated and injected into the site of the injury.
Herniated disc is a condition characterized by damaged intervertebral discs, causing them to bulge or break. The intervertebral discs within the spine column undergo a significant amount of daily stress. Over time, this stress is believed to cause the disc to rupture, bulge, or herniate. In other words, the material comprising the intervertebral disc expands, putting pressure on the spinal column as well as the surrounding nerves. This pressure from the bulging disc is believed to be the source of significant pain. Further, this condition is more commonly found among aging individuals. While physical therapy has shown some promise in terms of improving the condition of the herniated disc, it requires a significant portion of time. Other treatments include surgical procedures, which cut out and remove bulging or herniated disc material. This type of procedure involves a number of risks as the disc is significantly weaker following the surgery and removal of tissue, which is believed to place the individual at an increased risk for future difficulties. New techniques within the field of regenerative medicine include utilizing the patient’s stem cells and support cells (which includes platelets) to regenerate and rebuild the network of cells comprising the injured disc.
Plantar fasciitis is a common form of chronic pain within the heel and foot. The flat, thick connective tissue found on the bottom of the foot, which connects the ball of the foot to the heel is known at the plantar fascia. The plantar fascia creates support for the arch of the foot. When this connective tissue becomes strained, there is a risk for damage to occur in the form of tiny tears on the ligament itself. In general, treatments available for providing relief for the pain associated with plantar fascia only target the symptoms of pain. Thus, regenerative procedures are believed to be the ideal choice to treat the pain of plantar fascia, as they promote the body’s own process of healing damaged tissue. Indeed, several research studies have provided empirical support for the use of platelet rich plasma therapy as an effective therapy for plantar fascia.
Sacroiliac joint pain
The sacroiliac joint is large and located at the base of the spine, connecting the spine with the hip. In many instances of sacroiliac joint pain, the individual is able to identify the injury that occurred prior to the onset of pain. However, acute events do not account for all cases of sacroiliac joint pain. Presently, there are limited treatment options available for sacroiliac joint pain. Indeed, evidence in terms of the effectiveness of steroid injections, radiofrequency neurotomy, and pulsed radiofrequency for the treatment of pain related to this joint is generally poor. However, there is some evidence, albeit limited, that regenerative procedures are effective in providing the patient relief from pain. Further, some evidence exists that suggests that the benefits of prolotherapy last much longer than that of steroid injections.
Lumbar radiculopathy, which can also be known as sciatica, is believed to occur when a herniated disc (typically between the fifth lumbar (L5) and the first sacral spinal nerve (S1)) pushes against a nerve. This pain travels down the leg. The primary goal of therapy is to reduce the size of the bulging disc, thereby reducing the compressive effect the bulging disc had on the nerve root. While there are a number of treatments available for treating lumbar radiculopathy pain, should these treatments be ineffective in relieving patients from their pain, they may be an appropriate candidate for stem cell repair.
Cervical radioculopathy is a chronic pain condition that occurs when a disc in the neck is pushing against the cervical nerve causing pain to travel down the arms. This condition is commonly found among young adults either through a herniated disc or an injury. Older adults, however, struggling with these symptoms of neck pain, are expected to have osteophyte formation causing foraminal narrowing, decreased disc height, and degenerative changes in the intervertebral joints.
Failed back surgery
A small number of patients have back pain so severe and unremitting that they must have surgery in order to try and gain some relief. As a result of this surgery, some patients continue to suffer from ongoing symptoms of back pain. These cases are recognized as failed back surgery, as the goal of the original surgery was to provide the patient with relief from pain. In these cases, pain in the lower back is caused by scar tissue that develops around the spinal nerves of the epidural space following surgery. Other factors that likely explain pain that persists following back surgery include disc herniation, post-operative pressure that is persistently placed on the spinal nerve, and altered joint mobility. Individuals with a history of anxiety, depression, or difficulty falling asleep or staying asleep are considered to be at an increased risk for developing a chronic pain condition following back surgery. Symptoms of chronic pain that occurred as a result of failed back surgery primarily include diffuse, dull, and aching pain across the back and lower limbs. Additionally, some patients may experience sharp, pricking, or stabbing pain in the limbs. Provided that other treatments have failed at providing the individual with relief from pain, failed back surgery patients may be considered for treatment using regenerative medicine.
Procedure for Regenerative Medicine for Pain
In general, the procedure takes approximately 30 minutes. The expert physician generally sees patients at a clinic and is able to complete the procedure without the use of general aesthesia. Further, by completing this procedure on an outpatient basis, there is no recovery period. In fact, individuals are able to return directly to work and their usual activities following the procedure.
Generally, regenerative medicine involves extracting the patient’s own stem cells and other supporting cells from one of the known sites for stem cells. This material is then purified, concentrated, and injected into the damaged tissue. It is important that this concentration is not altered in any way. Most individuals report very little discomfort from this procedure. Some minor soreness at the site of the injection may be reported. Further, patients may experience mild bruising.
Benefits of Regenerative Medicine for Pain
Patients are expected to achieve a number of benefits through regenerative medicine, such as:
- Significant improvements in joint, tendon, and ligament function
- Renewal and repairs within the joint
- No significant incisions or trauma
- Very little pain or discomfort
- No general anesthesia
- Faster recovery time and very little downtime
- Very low risk for an allergic or adverse reaction
Indeed, both acute and chronic pain conditions are common and are considered a serious public health concern. It has been suggested that up to 90% of the population will experience a pain condition that interferes with their daily functioning at some point in their lifetime. Some estimates have suggested that back pain alone is associated with annual costs exceeding $100 billion, including medical expenses and loss of productivity. Moreover, chronic pain is associated with a number of negative impacts on the individual’s daily functioning both at home and at work. Chronic pain has been associated with missed work, losses in productivity, and increases in sedentary lifestyles.
There are a number of treatments available to provide patients with relief from chronic pain. Following an accurate diagnosis by a physician specializing in pain conditions, it is generally recommended that patients who were referred for regenerative medicine first undergo an initial consultation with an expert pain specialist. While there is evidence that these treatments are beneficial to a wide variety of pain conditions, there are a number of individuals whose pain does not respond to treatment. For these individuals with intractable pain, more aggressive and long-term forms of treatment are available to combat their debilitating symptoms. Further, regenerative medicine is not approved for all pain conditions. Your doctor will help determine which treatment is right for you.
In terms of the procedure, regenerative medicine involves an extraction of the patient’s own stem cells and other supporting cells from one of the known sites for stem cells. This material is then purified, concentrated, and injected into the damaged tissue. It is important that this concentration is not altered in any way. Most individuals report very little discomfort from this procedure. Some minor soreness at the site of the injection may be reported. Further, patients may experience mild bruising, again, at the site of the injection. This procedure is generally regarded as safe and can be done on an outpatient basis.
Historically, very few studies exist regarding the effectiveness of regenerative medicine on many different pain conditions. However, evidence is mounting regarding its effectiveness for a range of pain conditions that failed to respond to first-line interventions. Improvements to the system and its procedure are impending, given the significant advances in technology. Thus, regenerative medicine may emerge in future studies as an ideal method of treating chronic pain.
NOTE: Adult stem cells are autologous, meaning that they are drawn from an adult patient and then returned to that same patient in the form of treatment. Presently, the FDA does not have any approval requirements in terms of the collection of adult stem cells. The FDA has not approved the use of stem cells to combat aging or to prevent, treat, or cure any disease or medical condition mentioned.
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