Alpine Spine & Orthopedics - Top-Tier Stem Cell Therapies & Regenerative Medicine Expertise

Stem Cells in Regenerative Medicine

Evidence-based therapies for repair of neurologic & orthopedic conditions

Many new regenerative medicine techniques and technologies are being developed which can help stimulate repair and regeneration of injured or degenerated tissues, and we keep up to date with the latest evidence-based research and clinical studies to provide you with the latest ground-breaking interventions. Regenerative medicine utilizes several approaches for reconstructing damaged tissue and treating painful or degenerative conditions, including the use of specific types of stem cells, growth factors, signaling molecules, peptides, plasma, platelets, exosomes, biomaterials, hydrogels, and/or engineered 3D matrix constructs, along with minimally-invasive image-guided placement of these products directly at the site of injury or degeneration.

"Orthopedic surgeons are at an exciting crossroads in medicine, where biologic therapies are evolving and increasingly available. Time-tested interventions such as arthroplasty have shown good results and still have a major role to play, but newer regenerative approaches have the potential to effectively delay or reduce the requirement for such invasive procedures." --Aaron Krych and Mario Hevesi, Orthopedic Surgeons at the Mayo Clinic, International Orthopaedics, Feb 2021 [1].

"Orthobiologics" is a term for regenerative agents that can accelerate healing and recovery from injuries and can help avoid surgery, instead healing the root cause of the problem more naturally and more completely. For example, mesenchymal stem cells (MSCs) are multipotent cells that can be harvested from your own body and differentiate into a variety of cell types including osteoblasts (for bone), chondrocytes (for cartilage), tenocytes (for tendon), myocytes (for muscle and heart), endothelium and smooth muscle cells (for blood vessels and vascular perfusion), and possibly even neuroglial cell types (for neural tissue) [74-90, 154-163]. We use highly specialized protocols to painlessly harvest, purify, and concentrate stem cells, exosomes, peptides, and growth factors from bone marrow aspirate for your particular needs. We optimize stem cell grafts by sticking them onto the injured tissue under image-guidance, which helps the cellular grafts integrate and rebuild new tissue both by cell receptors and biomechanical cues that adapt cells to the appropriate lineage. By using your own mesenchymal stem cells you use fresh healthy cells that are primed to rebuild your own tissue without immune rejection and thereby avoid stem cell rejection and immune reactions to foreign donor cells.

We are the first institute to combine stem cells with platelet-rich fibrin (PRF) to synergistically increase stem cell survival, integration, and release of growth factors at a wide variety of target sites with an array of complex image-guided injections. When injected into joints and cartilage defects, MSCs with PRF can help patch or pave these injuries for enhanced healing (like re-paving a pothole in the road) and thereby regenerate new hyaline cartilaginous matrix even in full-thickness articular cartilage defects [2-10, 24-50, 131a-b], and this combination of Stem Cells + PRF is also being studied in injuries of tendon, ligament, labrum, meniscus, disc, nerve, and many other tissues [53-73]. Without an adherence matrix like PRF, the stem cells are not fully enabled to properly bind and integrate into these orthopedics tissues and instead tend to undergo a programmed cell death called apoptosis and anoikis.

We are the premier clinic with both the surgical expertise and the stem cell expertise to optimally combine stem cells with your own purified PRF under proper conditions to maximize their survival, viability, and repair capacity with minimal processing, then immediately inject these fresh cells directly at injury sites under image-guidance for maximizing their tissue repair properties and proper 3D tissue reconstruction based on your specific injuries. PRF acts as a biologic glue and anchor to hold the stem cells at the injury site and aid their integration. Dr. McMurtrey spent several years researching stem cell cultures and applications at some of the top university labs in the world, including at the University of Oxford where his thesis on stem cells, bioregenerative tissue engineering, and 3D tissue reconstruction earned the highest honor of distinction and resulted in several publications in top-ranked prestigious research journals.

PRF can capture your own growth factors and circulating hematopoietic and bone-marrow stem cells [11-16] and PRF uses your own cells and activated platelets to focally release growth factors such as BMP, FGF, VEGF, PDGF, eNOS, and others which are released locally over the next few days to weeks. These factors can help accelerate and strengthen tissue repair, and these further activate recruitment and differentiation of MSCs as well as expression of several tissue remodeling genes [3-7]. MSCs may also have many other good anti-inflammatory, immunomodulatory, reparative, and/or vascularization effects. These stem cells not only can help rebuild damaged tissues, but also secrete growth factors and additional signaling cues in packets known as exosomes, which can further suppress deleterious inflammatory/degenerative pathways to help kickstart cells out of a degenerative rut and back into a high-productivity regenerative phase that favors tissue healing, cellular repair, and strengthening of damaged structures. Thus in addition to powerful cell-based therapies, exosomes and peptides are also being studied as a cell-free solution for injection into or around sites of injured tissues and organs [91-102]. All these options can be administered in our clinic using minimally-invasive injections under high-resolution image-guidance for optimal repair of numerous types of injuries.

CLINICAL EVIDENCE FOR STEM CELLS:

There are several clinical studies in progress on the benefits of stem cell injections for many ailments like arthritic and damaged joints, tendon tears and connective tissue injuries, spine and spinal cord injuries, peripheral nerve injuries, stroke, brain injuries, neurodegenerative diseases, and many other forms of organ and tissue damage. For example, studies have already shown benefits and safety in knee injuries and knee osteoarthritis [37-40, 65-73]. Further clinical studies are still ongoing for several spine, nerve, brain, spinal cord, central nervous system, and neurological conditions like stroke, traumatic injury, and neurodegeneration [42-43, 74-90, 97, 134, 154, 162-163], and autologous hematopoietic bone marrow stem cell transplants have also demonstrated some of the best effects on controlling auto-immune conditions including rheumatoid arthritis, scleroderma, Crohn's disease, and neuro-immunological diseases like multiple sclerosis by rebooting the immune system through a re-diversification of naive and regulatory immune effector cells and other immunosuppressive effects [139-142]. Thus stem cells not only integrate and rebuild tissues directly for long-lasting repair, but also release growth factors, exosomes, and other factors that trigger long-lasting adaptive tissue repair responses.

Stem cells have also shown significant benefits in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), which is characterized by degeneration of upper and lower motor neurons, with mesenchymal stem cells possibly delaying progression of this disease and even giving partial recovery of neuron function [112-116]. Bone marrow stem cells appear to be especially effective in ALS, with one clinical study showing that 87% of stem-cell treated ALS patients had at least 25% improvement in function within 6 months of autologous bone-marrow-derived mesenchymal stem cell treatment [113]. These benefits are thought to arise at least in part due to the neurotrophic factors, growth factors, and other signaling cues that are produced and excreted by the stem cells to accelerate tissue repair [113-114, 117]. Stem cell factors such as VEGF, angiogenin, and TGF-β seem to be higher in those patients who have the best response to the stem cell therapy, and these stem cells can be delivered by epidural, intrathecal, intravenous, intranasal, intramuscular, and much more specific image-guided injections [113-114]. Mesenchymal stem cells have also been used to form a "stem cell patch" to repair degenerative disc defects, annular tears, and spina bifida defects around the spinal cord to prevent paralysis in infants and possibly even reverse damage to spinal cord and nerve function [135-138, 143-145]. One of the mechanisms of stem cell healing for herniated spinal discs and nerve compressions may be not only direct repair of the injured tissues and strengthening of the disc, but also proper suppression of the painful inflammatory immune signaling around pathological sites [137].

Bone marrow stem cells have also been used to successfully treat traumatic spine injuries, traumatic brain injuries and concussions by strengthening spinal tissue repair and preserving critical brain architecture as well as suppressing inflammatory signaling [42-43, 74-90, 97, 134-138, 162], and this effect may be augmented by temporary non-invasive blood-brain barrier opening using ultrasonic trans-cranial doppler while infusing the cells directly in the clinic. In addition, the body’s own stores of fat tissue, called subcutaneous adipose tissue as well as stromal-vascular fractions (SAT and SVF), also contain multipotent stem cells of the Schwann cell class that can differentiate into both neurons and glial cells, making yet another potential source of powerful cells for potentially treating a variety of neurological injuries and conditions [118-119]. We are particularly interested in using the power of your own purified bone marrow stem cells to stimulate BDNF release, promote remodeling of neural networks and gliosis, and inhibit neuroinflammation [113, 163-167] for applications in spinal cord injuries and traumatic brain injuries.

Furthermore, a recent study showed that many commercial stem cell products, including those derived from wharton's jelly, umbilical, amniotic, or other perinatal sources, actually contained very few (if any) viable stem cells at all since most die in the storage and processing [36]. This study then compared fresh stem cells from a patients' own bone marrow mesenchymal stem cells and showed that these stem cells were abundant even in elderly patients and retained dramatic abilities to live, grow, proliferate, and differentiate into tissue-specific subtypes [36], plus these cells can build new tissue without causing an immune reaction (unlike foreign donor cells). Bone marrow stem cells are already primed for repair of many types of mesenchymal tissues, thus your own body is the best source for stem cell harvesting and injury repair in most cases, especially orthopedic-type tissue injuries, but these cells need to be placed into the proper location with proper conditions to best repair tissues. If there is any doubt about the power of stem cells, remember that well into late age the body retains stem cells that can create entirely new offspring with perfect forms of every tissue structure-- we just need to harness the potential of our own stem cells to optimize and steer their incredible capabilities. Interestingly, animals like salamanders and axolotl are able to regenerate entire limbs, and this regenerative process is driven primarily by hematopoietic and myeloid stem cells, which in the human is the equivalent of bone marrow stem cells that drive mesenchymal cell lineages of ligament, cartilage, muscle, bone, and connective tissues [52].

Depending on your needs, we can harvest stem cells from your own bone marrow with a simple needle and numbing sedation, and we use specialized surgical protocols to maximize isolation, yield, viability, and long-term survival of the stem cells with minimal processing and immediate injection of the fresh cells back into your body in the same procedure. These types of autologous bone grafts and bone marrow procedures have been done in many types of surgical procedures for many different reasons. Research has elucidated many ways that these stem cells are primed for tissue repair and can be used to help stimulate your own natural healing, reconstruction, or repair of injured or degenerated tissues and joints such as muscle, ligaments, tendons, nerves, bones, cartilage, and fibrocartilage [2-10, 17-51, 83-90, 120-132]. Interestingly, organs like the heart and brain may also benefit from stem cell treatments, as there are also other hormones and peptides in bone marrow like osteocalcin which have been shown to enhance memory, brain function, cardiac function, fitness, metabolism, healing, and tissue remodeling after ischemic damage [120-132, 151-161]. Bone marrow stem cells have also shown promise in repairing and healing many orthopedic injuries including non-union fractures, failed surgeries, pseudoarthrosis, spondylolysis, pars defects, joint injuries, cartilage defects and arthritis, as well as many other complex conditions [124, 146-153]. These bone-marrow cells also have good evidence for helping repair and rebuild osteonecrosis, avascular necrosis, bone marrow failure, and subchondral injuries in bones and joints [168-178], which provides immense hope for patients with these recalcitrant and refractory conditions. The addition of certain peptides with stem cells may further enhance bone reunionization and healing of bone fractures, ligament tears, and tendon attachment avulsions [178-193]. Other common sites for bone marrow stem cell injections include spine, discs, nerves, knees, hips, shoulders, ankles, feet, sacroiliac joint, elbows, hands, covering a wide variety of traumatic injuries and tissue defects, avulsions, fractures, tears, neuropathies, and other chronic non-healing injuries. All these procedures are best done under live image-guidance to ensure accurate and specific targeting of the injury site with appropriate localization of cells and scaffolding with growth factors for optimal regeneration and healing.

OVERVIEW OF SOME STEM CELL SIGNALING PATHWAYS:

Finally, the history of stem cell research is also fascinating and worth briefly covering here. The earliest concepts of stem cells arose in the early 1900s when studying the ability of bone marrow to continually produce new blood cells. Then as a graduate student in 1958, John Gurdon discovered in his research work at Oxford that mature cells retain all the information needed to make any cell type of the body encoded somewhere deep within their own DNA [103]. Many years later, a physician named Shinya Yamanaka was pursuing his training in orthopedic surgery when he began to notice how many diseases and conditions exist that physicians actually have no ability to fix or heal (including everything from spinal cord injuries and traumatic brain injuries to orthopedic conditions and autoimmune diseases), and he lost confidence in the surgical approach and instead turned his efforts towards curing diseases from a much more thoughtful scientific approach, which ultimately resulted in one of the greatest discoveries of all time (winning a Nobel Prize in 2012): mature adult cells can in fact be reverted back to a full pluripotent stem cell state, capable of becoming any type of cell or tissue, by just introducing a few simple factors into the cell [104]. Dr. McMurtrey has since replicated this work in his own lab, taking adult blood cells and reprogramming them back into pluripotent stem cells, then differentiating and directing them to reconstruct new 3D tissue types using a variety of biochemical, biomechanical, and nanopatterning cues [105-111].

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*Disclaimer: We seek to always provide the highest-quality evidence-based care to our patients customized for their specific conditions, injuries, and diagnoses, which may include FDA-approved therapies as well as additional investigational, alternative, or regenerative therapies. We always discuss potential risks and benefits of all these options. The information presented here is for informational use and cites the ongoing cutting-edge research and medical advancements on these relevant topics. There are many treatments, interventions, and protocols routinely practiced in medicine and surgery which the FDA has not studied nor formally approved yet which have demonstrated overwhelming evidence of efficacy and clinical benefit, while many standard treatments and common surgeries can actually have high rates of failure and complication. The FDA does not regulate the practice of medicine but rather regulates medical marketing of devices and drugs. The FDA does not conduct clinical trials or attempt to discover new treatments, but rather requires companies or other entities to fund marketing approvals. Breakthrough technologies typically require years to decades of research work to optimize the technology and collect enough data to prove efficacy and superiority, which in some cases can optionally be submitted to the FDA if there is sufficient financial backing to market a specific product or drug. Thus the FDA has not yet studied, evaluated, or formally approved many regenerative therapies currently practiced by many of the top physicians and surgeons in the United States and around the world. Some therapies, products, or interventions may still be considered investigational or "off-label" even with substantial evidence of efficacy, and many different applications of regenerative therapies continue to be researched by our institute and other top institutions around the world. The rapid evolution and advancement of medicine demands that physicians continually update their knowledge and practice techniques to adapt to future improvements and advancing technologies. These statements have not been evaluated by the FDA, and the treatments and products presented here are for informational purposes and not guaranteed to diagnose, treat, cure, or prevent any specific disease or condition. All injuries and conditions should be formally evaluated by a knowledgeable medical professional whereby standard treatments and additional therapeutic interventions may be considered with the diagnosis and treatment plan.