Regenerative medicine is an emerging area of science that holds great promise for treating and even curing a variety of injuries and diseases. It uses natural tissue engineering, cellular therapies, and medical devices to repair tissue or organs damaged as a result of disease, trauma, or congenital issues. In using one of these approaches or a combination of them, regenerative medicine can amplify our natural healing processes and improve health and function.
In this relatively new field, experts from many different disciplines, such as biology, chemistry, computer science, engineering, genetics, medicine, robotics, and other fields, work together to find solutions to some of the most challenging medical problems.
Regenerative medicine includes using stem cells and other technologies—such as engineered biomaterials and gene editing—to repair or replace damaged cells, tissues, or organs. In fact, stem cell-based approaches are under development in labs around the world, and some have already moved into clinical trials.
The 21st Century Cures Act, passed in December 2016, established the Regenerative Medicine Innovation Project (RMIP) to accelerate the field by supporting clinical research on adult stem cells while promoting the highest standards for carrying out scientific research and protecting patient safety. In recognition of the integral role of the Food and Drug Administration (FDA) in the successful development of this field, the National Institutes of Health is leading the RMIP in coordination with the FDA.
Role of Regenerative Medicine in Orthopedics
At CalSpine MD, Dr. Ball’s goal is to provide the latest in minimally invasive therapies that will replace, repair, or promote tissue regeneration for acute and chronic orthopedic conditions as well as spinal pathologies using acellular amnion-derived allograft, platelet-rich plasma (PRP), and other methods that amplify the body’s natural biology to repair injured or damaged tissue. When used in correct concentrations and doses, these therapy options may help speed up the healing process of broken bones, injured muscles, tendons, and ligaments (musculoskeletal injuries) and discs in the spine.
Acellular Amnion-Derived Allograft
Acellular Amnion-Derived (Placental Rich) Allograft is an injectable, all-natural liquid matrix used to heal injured, inflamed, or chronically painful areas. It may be mixed with your blood or preservative-free saline to reduce inflammation and promote healing. In some cases, it may be used in place of corticosteroid injections to reduce inflammation without weakening ligaments, tendons, and other connective tissue. It is purified, without cells (acellular), and will not cause an immune reaction or rejection reaction.
Amniotic tissue allografts should not be confused with stem cells from embryos. This type of regenerative matrix comes from the amniotic sac, NOT an embryo or fetus.
These allografts contain growth factor, and extracellular matrix components. The tissues are collected from fully consented mothers undergoing scheduled Cesarean section births of full-term healthy babies. Donors are tested for relevant communicable diseases by an FDA-registered laboratory. Only fully screened and approved donors are accepted as donors.
Acellular Amnion-Derived Allograft is effective in treating
- Focal chondral defects
- Early osteoarthritis
- Soft tissue injuries including tendons (e.g., rotator cuff tears), muscles and ligaments
- Spinal Pathologies (e.g., lumbar degenerative disc disease or spondylosis)
Benefits of Acellular Amnion-Derived Allograft
These products, made from substances that are naturally found in your body, help to improve the quality of healing, offering better and stronger tissue and less scar tissue. For athletes, they offer an alternative to steroid injections–they are joint preserving, reduce inflammation, and do not harm cartilage. Repeated cortisone or steroid injections to a joint cause ruptures of ligaments, cartilage damage, or nerve damage.
Platelet-Rich Plasma (PRP) Therapy
Platelet-rich plasma therapy (PRP) can help injured joints and other problems. It uses part of your own blood to reduce pain and speed up healing. PRP may help if you have
- Meniscus tears in your knee
- Rotator cuff tears in your shoulder
- Plantar fasciitis in your foot
- Injuries in your spine, hip or elbow
- Sprains and strains in ligaments and tendons
How It Works
The process begins with a sample of your blood. It is spun around in a centrifuge that separates platelets, plasma, and red and white blood cells. The platelets are then concentrated and mixed with some of the plasma. This mixture is called “platelet-rich plasma.” Dr. Ball injects this into the site of your injury. After the injection, your immune system (the system that keeps your body healthy) reacts quickly, and special white blood cells called “macrophages” rush in to take away damaged cells. Macrophages help prep the site for healing. Then, stem cells and other cells begin to multiply. Over time, they repair and rebuild the injured tissues.
Benefits of PRP Therapy
Patients may experience several benefits from PRP therapy, including:
- It is quick, and you can go home the same day.
- It may help your injury heal faster.
- It can help treat and eliminate the cause of your pain.
For some patients, more than one treatment may be necessary before they heal completely.
The Healing Process
When you have a musculoskeletal injury, there is bleeding in the injured area. This bleeding is the foundation for the healing process, and it provides a way for healing factors to reach the injury site. These healing factors in combination with bleeding are all necessary for healing. Acellular amnion-derived allograft, regenerative extracellular matrix, and PRP may enhance the potency and speed of this healing process. They include matrix materials, growth factors, and stem cells.
Matrix material (or conductive material) provides housing or scaffolding for stem cells while they grow into mature cells. If stem cells do not have a house to grow in, they cannot develop into repair cells that can heal bone, muscle, tendon, or cartilage. These cells are also known as mesenchymal or undifferentiated cells.
When a patient breaks a bone, the healing process begins, and stem cells should be able to make new bone and promote healing. However, if a significant portion of the broken bone is lost due to a bone being fragmented, a large gap may result. In this instant, the gap must be filled with matrix to house stem cells. There are several substances that can be used to fill such gaps, during surgery including:
Bone Grafts. There are two types of bone grafts–an autograft and an allograft.
An autograft is a bone graft that is harvested from the patient, usually taken from the patient’s iliac crest, which is a part of the pelvis. Harvesting the bone graft requires an additional incision during the operation to treat the injury. This not only increases the time of surgery but it can also cause increased pain or risk of infection after the operation. Generally, patients have a good outcome; however, the harvesting site usually takes a while to heal.
An allograft is a bone graft that comes from cadaver bone supplied by a bone bank (bone tissue that is donated upon death). If the needed bone graft is available, this is the preferred method, as it avoids the risk of pain at the donor site. It does not heal as completely as bone from the same patient.
Artificial Matrix Material. Artificial matrix material, such as tricalcium phosphate or hydroxyapatite, can also be used to fill a large void between bone ends. It can form a material that closely resembles bone, and it contains holes that are the right size for stem cells to enter and develop into mature cells.
Growth factors are proteins. They play an important role in the healing process, as they call stem cells to the injury site to develop/repair cells. This process is called chemoattraction.
Chemoattraction only works well when there is sufficient blood supply around the injured area for the protein to attract the mesenchymal stem cells, providing a way to travel to the area where they are needed.
When there is insufficient blood supply, we rely on regenerative medicine to explore ways to help the body heal better–harnessing the power of the body to naturally heal and then accelerate it in a clinically relevant way.
Bone Morphogenetic Proteins (BMPs). BMPs are genetically engineered proteins that aid in bone healing. These synthetic proteins help with muscle, tendon, and cartilage healing. In large enough quantities, they are effective in speeding up the healing process of damaged bone, especially in fractures that have a difficult time healing.
Stem cells are undifferentiated cells that are capable of giving rise to indefinitely more cells of any type. These immature cells can develop into many different cell types in the body and have the greatest potential for promoting healing, as they function as an internal repair system replenishing other cells where needed to promote healing. Each divided cell, therefore, has the potential to become another type of cell needed to help in healing–bone, muscle, ligament, and cartilage.
Stem Cells Speed Up The Healing Process
Doctors have developed ways to retrieve stem cells and deliver them to the injury site faster and in greater numbers and concentration to speed up the healing process. Stem cells can be retrieved either from harvesting them from a patient or through a stem cell donor program.
Stem Cell Harvesting. Stem cells can be harvested from bone marrow located in the centers of long bones, such as the bones in your arms, forearms, thighs, and legs. They can also be harvested from the pelvic bone, which contains the highest concentration of stem cells.
Once stem cells are drawn out of the bone marrow with a needle, the orthopedic surgeon inserts this large supply of stem cells into the injury site.
Stem Cell Donation. Doctors can also use donated stem cells to promote healing. These donated cells come from donors after they pass away. When the cells are harvested, they are treated so that they will not create an immune or allergic reaction in the patient.
Stem Cell Therapy
Stem cell therapy is a cellular therapy emerging as a frontline regenerative medicine source. Stem cells are harvested and then injected at the site of diseased or damaged tissue, so the reconstruction of the tissue is feasible under the right circumstances. Cells can be collected from blood, fat, bone marrow, dental pulp, skeletal muscle, and other sources. Our bodies use stem cells as one way of repairing itself–replacing, repairing, reprogramming, or renewing diseased cells.
Stem Cell Types
There are two stem cell categories, embryonic and mesenchymal.
Embryonic Stem Cells are harvested from human embryos grown in vitro (refers to the technique of performing a given procedure in a controlled environment outside of a living organism). They are pluripotent, meaning they have the ability to become a cell for any part of the body (nerve, muscle, blood, etc.). These stem cells are not used for treatment in the United States.
Mesenchymal Stem Cells (MSCs) are adult stem cells. They are multipotent (not pluripotent), meaning they have the ability to develop specific types of cells, for example, a blood stem cell can develop into a red blood cell. MSCs can differentiate in vitro into tendon and ligament cells, muscle cells, bone cells, cartilage cells, and fat cells.
MSCs are retrieved from Bone Marrow Aspirate Concentrate (BMAC) aspirated from the iliac crest, and adipose (fat) tissue derived from the abdomen or infrapatellar (below the patella–the bone at the front of the knee) fat pad.
Misconceptions About MSCs
One of the biggest misconceptions about MSCs is that the stem cells directly convert into the diseased or injured tissue in question, and the
- Injection of MSCs in an osteoarthritic knee contributes directly to the regeneration of cartilage tissue; and
- Infusion into cardiac patients of MSCs will directly convert into functional heart muscle cells to replace the cells that die from the ischemia of the heart attack.
To clarify, MSCs after injection
- Do hone in on active sites of injury or inflammation.
- Do not differentiate into the tissue at that site.
- Do secrete bioactive factors.
- Do stimulate local stem cells to make healing tissue.
- Do offer therapeutic effects that can be analyzed as site-specific clinical outcomes.
Justifying the Use of Stem Cells
We rely on evidence-based medicine to justify the use of stem cells. We use this evidence in making clinical decisions and integrate this evidence with clinical experience. Evidence-based medicine is the conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients. The practice of evidence-based medicine means integrating individual clinical expertise with the best available external clinical evidence from systemic research.
The most controversial aspect of evidence-based practice is that individual studies frequently contradict each other. It is, therefore, our jobs as clinicians to determine which studies provide the best answer, evaluating study design and absence of bias.
The general principles for determining the best studies and evidence are those that are controlled versus uncontrolled, prospective versus retrospective, and randomized versus nonrandomized.