Glaucoma is a group of eye conditions that damage the optic nerve and lead to progressive, irreversible loss of vision. With over 80 million people affected by the condition, glaucoma is the second-leading cause of blindness, behind only age-related macular degeneration.
Although there are several different risk factors, the most understood and treatable risk factor for glaucoma involves controlling the eye’s intraocular pressure, or IOP. When left unaddressed, glaucoma progressively leads to vision loss resulting from damage to axons and associated retinal ganglion cells (RGCs) responsible for transmitting visual information from the eye to the brain. While current treatments for glaucoma are primarily pharmacologic, laser-based, and surgical procedures designed to lower and/or control IOP, they are unable to reverse or restore vision lost as a result of previous damage to the affected axons, RGCs, and the collective optic nerve.
Chanling, Slush, and Zack’s article aim to assess current literature and developments exploring the potential of using human stem cells to further study, and potentially treat, glaucoma and other conditions affecting the optic nerve. For the purposes of this review, the authors divide their discussion into four key areas: stem cell-derived trabecular meshwork cells to control IOP; stem cells as a source of RGCs; stem cell-derived RGCs for transplantation and vision restoration; and stem cells as a source for neurotrophic factors.
Stem Cell-Derived Trabecular Meshwork Cells to Control IOP
Insufficient drainage of the eye’s aqueous humor results in increasing IOP. Current medication for the treatment of this condition reduces aqueous production and or increases aqueous outflow through the trabecular meshwork (TM). Since the TM is a known source of stem cells, researchers hypothesize that these cells and specifically mesenchymal stem cells (MSCs) could be used to repair IOP function and potentially restore vision lost as a result of this condition.
Recent studies have shown promising results, leading researchers to believe that there is a strong possibility of using stem cell-derived TM cells to preserve optic nerve function and reduce IOP.
Stem cells as a Source of RCGs
In addition to assisting with regulating IOP, researchers believe that stem cells may also be able to preserve, and even restore, RCG function – which is ultimately responsible for vision loss caused by glaucoma.
Specifically, the authors point to a number of animal studies that have demonstrated positive responses in a number of signaling pathways and neuroprotective compounds responsible for promoting RNC function and survival. The authors also point out that, while these studies are promising, none have made it to the clinic.
Stem Cell-Derived RGCs for Transplantation and Vision Restoration
While still a relatively new concept, there has been tremendous progress made in the ability to transplant RCEs and photoreceptor cells in the eye. Coupled with the observed differentiation of RGCs, researchers believe the ability to successfully transplant RGCs, with the intent of restoring glaucoma-related vision loss, is not far off.
The authors note that, while these findings are promising, there is still much work and additional research to be completed in this area and that the process of transplanting RCGs is much more complicated than the process used for transplanting retinal pigment epithelial cells (RPEs) and photoreceptors cells.
Stem Cells as a Source for Neurotrophic Factors (NTFs)
Research suggests that deprivation of the NTF required for maintenance and survival of neurons is a leading factor in the progression of glaucoma. As a result, additional research has reported that supplementing additional BDNF and other NTFs, through the use of stem cells appears to support the health and survival of RGC. The authors point out that, while promising, the process required during this procedure is challenging, primarily because it requires the blood-retinal barrier to be circumvented.
The authors of this review conclude that, as a result of the rapidly advancing pace of ocular stem cell research and related ongoing advancements in stem cell technology, there are ongoing opportunities to better understand and improve upon the current glaucoma-related biology and to develop pharmacological models that include cell-based therapies in the effort to restore vision to those affected by glaucoma.
Multiple sclerosis (MS) is a nervous system disorder in which the information that flows between the brain and body becomes disrupted. It’s estimated that at least one million people in the U.S. are living with MS. In this condition, the immune system mistakenly attacks healthy tissue in the brain known as the myelin sheath, or the protective coverings for the nerves. This immune system attack also results in inflammation which can further damage nerve cells. Here is how regenerative medicine is used to manage multiple sclerosis.
People with MS can experience a wide range of unpredictable symptoms which may include:
Vision changes
Tremors
Numbness or weakness in the limbs
Slurred speech
Fatigue
Gait changes
Tingling or pain throughout the body
Experts aren’t sure what causes MS, though it’s believed that a combination of genetic and environmental factors contributes to a person’s risk. Women are also two to three times more likely to have the condition.
Regenerative Therapy for MS
Fortunately, the outlook for people with MS has improved over the years. Medications are available to both manage symptoms and modify the progression of the disease. In addition, patients may also be able to explore options such as regenerative therapy to halt the progression of MS and control symptoms without the side effects that come with medications.
Regenerative therapy is used to trigger the natural repair processes within the body, thereby replacing damaged cells with new, healthy ones. In particular, mesenchymal stem cells could be used to repair and replace damaged nerve cells. These cells also have anti-inflammatory properties and can restore the myelin on nerve cells to essentially reprogram the immune system. Patients could then see benefits such as:
Improved coordination and concentration
Reduced muscle spasms and pain
Reduced numbness and tingling
Improved bladder function
Better energy levels
Better balance and range of motion
Improved sense of touch and vision
Slowing or decreased rate of progression
Reduced headaches
Currently, patients may undergo regenerative therapies such as stem cell injections. These cells can regenerate lost or damaged cells, including myelin sheath tissue. They can also modulate the immune system to halt the attack on healthy cells, returning it to a state of rest and allowing the body to restore its proper levels of wellness.
Patients who have undergone stem cell therapy for MS have witnessed noteworthy improvements in the areas of neurologic disability, functional scores, and overall quality of life. Moreover, side effects are mild and generally include headache and fatigue.
While research into regenerative medicine to manage Multiple Sclerosis is ongoing, the findings revealed so far suggest that stem cell therapy and similar treatments hold considerable potential for helping people with MS and other autoimmune disorders.
Spinal cord injury (SCI) continues to be a significant cause of disability. In fact, it is estimated that annual SCIs account for nearly 18,000 injuries in the United States and between 250,000 and 500,000 injuries worldwide[1]. Additionally, an estimated 294,000 people in the United States are currently living with some form of SCI, with males accounting for nearly 80% of all SCI injuries[2].
Despite a large number of SCIs occurring each year, therapeutic treatment options remain limited and primarily ineffective. Recently, improvements in the understanding of the promising role stem cells play in the healing process have led to significant developments in improving healing and restoring function lost as a result of Spinal Cord Injuries; specifically, the therapeutic treatment of SCIs with mesenchymal stem cells (MSCs) in animal models has demonstrated promising results.
Building off of the success observed in previous studies, Honmou Et al.’s recent study (2021) sought to further explore the safety and feasibility of intravenous infusion of MSCs is SCI patients; the study also explored the patients’ functional status after receiving IV infusion of MSC.
Specifically, Honmou Et al.’s phase 2 study delivered a single infusion of autologous MSCs cultured in auto-serum, to 13 SCI patients. After infusion, the study assessed the feasibility and safety of this procedure over a six-month period by using the American Spinal Injury Association Impairment Scale (ASIA) and International Standards for Neurological Function Classification of Spinal Cord (ISCSCI-92). The researchers also used the Spinal Cord Independence Measure (SCIM-III) as a way to assess the ability of daily living after receiving MSCs infusion.
Although this was a small, early, unblinded, and uncontrolled study, the researchers point out that the intravenous infusion of autologous bone marrow-derived MSCs, expanded in auto-serum, into SCI patients appeared to be safe and feasible with none of the patients exhibiting abnormal cell growth or neurological deterioration. Additionally, and similar to what’s been observed in prior studies conducted on animal models, the findings appear to support the rapid improvement of neurological function within a few days after IV infusion. The researchers also pointed out this study had several limitations, including potential observer bias and potential improvements resulting from surgical interventions.
The researchers point out that although the specific mechanism for this observed improvement in neurological status is not clear, several studies suggest that secreted neurotrophic factors from MCSs might be associated with the rapid improvements. Additional studies have also demonstrated that IV infusion of MSCs in patients with SCIs might also encourage changes in gene expression that encourage functional improvements, an observation that was consistent with the findings of this study.
In conclusion, the authors reiterate that the observed safety, feasibility, and initial indications of functional improvement after MSC infusion support the importance of additional, larger future studies designed to examine potential efficiencies in patients with SCI. Source: (2021, February 18). Intravenous Infusion of Auto Serum-expanded … – ScienceDirect.com. Retrieved March 23, 2021, from https://www.sciencedirect.com/science/article/pii/S0303846721000925#!
Osteoarthritis (OA), the most common form of arthritis, affects over 32 million people in the U.S. each year. Characterized by a progressive degeneration of cartilage resulting in pain, stiffness, and swelling in the joints, and most frequently occurring in the hands, hips, and knees, OA has no pharmacological, biological, or surgical treatment to prevent progression of the condition. The authors of this case report focus specifically on potential treatment options for OA of the knee.
With the emergence of stem cell-based therapies for a multitude of health conditions, stem cells, and specifically mesenchymal stem cells (MSCs), have demonstrated immunosuppressive activities that could prove beneficial in supporting the regeneration of cartilage tissue in and around joints in the body.
Research has demonstrated that MSCs are effective in differentiating into essential connective tissues like fat, cartilage, and bone; MSCs have also demonstrated immunomodulatory and anti-inflammatory effects, the ability to self-renew, and plasticity, making MSCs a potentially powerful treatment of OA in the knee (and other parts of the body).
This specific case study details cartilage regeneration in the knee of a 47-year-old woman diagnosed with OA when treated with bone marrow-derived MSC cells. For the course of this treatment, autologous MSCs were collected from bone marrow harvested from the iliac crest. After processing and preparing the MSCs, the sample was confirmed to be free of microbial contamination and was prepared and transplanted into the patient’s knee joint.
Periodic follow-ups with the patient revealed no local or systemic adverse events associated with the MSC transplant procedure. The authors of this case report found that the patient’s functional status of her knee, the number of stairs she could climb, reported pain on a visual analog scale, and walking distance all improved in the two months following the MSC transplant procedure.
Additionally, twelve months after the transplant, the patient demonstrated a positive change in WOMAC (3 to 2), a continued increase in the number of stairs climbed (5 increasing to 50), and visual analog (80 mm to 11 mm). The patient also demonstrated improved gelling (or the amount of time it takes for synovial fluid to thicken as a result of rest) in the knee from 8 minutes to 30 minutes; knee flexion also increased 20° (100° to 120°). Periodic MRIs taken after the transplant procedure demonstrated an extension of the repaired tissue over the subchondral bone.
Mehrabani, et al. conclude that MSC transplantation for treating OA in the knee appears to be a simple, safe, effective, and reliable treatment option that has demonstrated pain relief, improved quality of life, and significantly improved quality of cartilage without hospitalization, pharmaceuticals, or surgery.
Spinal stenosis occurs when the spaces within the spine narrow, resulting in pressure on the nerves running through the spinal column. The condition often develops in the lower back (lumbar stenosis) or neck (cervical stenosis).
People with spinal stenosis may not experience any symptoms, while others have pain, muscle weakness, numbness, and tingling. The condition is typically a result of osteoarthritis, the wear-and-tear deterioration of joints that occurs over time. Some doctors may recommend surgery to create additional space for the nerves.
Spinal Stenosis Symptoms
The symptoms of spinal stenosis may vary based on where the issue is located.
Symptoms of Cervical Stenosis
With stenosis of the upper spine or neck region, patients often experience:
Weakness in the extremities, such as a hand, foot, arm, or leg
Balance issues
Numbness or tingling in the extremities
Neck pain
Bowel or bladder issues in extreme cases
Symptoms of Lumbar Stenosis
When stenosis occurs in the lower back, patients may have:
Weakness or numbness in the foot or leg
Pain or cramping in one or both legs while walking or after long periods of standing
Back pain
Causes of Spinal Stenosis
Some people are naturally born with a narrow spinal canal, but in many cases, spinal stenosis is a result of outside factors that have caused the narrowing. Possible reasons for stenosis may include:
A herniated disk: The soft cushions between vertebrae often dry out and are less able to absorb shock over time. If a disk’s exterior cracks, the material may escape and put pressure on the nerves or spinal cord.
Bone overgrowth: Osteoarthritis is commonly associated with bone spurs, which can make their way into the spinal canal. Paget’s disease, a bone disorder, can also result in bone overgrowth.
Ligament thickening: The cords that hold the spine together may thicken over time, bulging into the spinal column and creating pressure on nerves.
Spinal injuries: Trauma caused by car accidents and other injuries can damage the vertebrae, leading to issues such as displaced bone or fractures that can impact the spinal canal. Also, the swelling of tissue following back surgery can put pressure on the nerves in the spine.
Tumors: Development of tumors in the spinal cord’s membranes can also occur, though they are uncommon.
In addition to these causes, certain factors also increase a person’s risk for spinal stenosis. Being over the age of 50, experiencing a back injury, and having a congenital spinal deformity such as scoliosis are all considered risk factors. Genetic diseases that impact bone or muscle development can also lead to spinal stenosis. If you want to learn more then contact a care coordinator today!
Autoimmune diseases occur as a result of the body’s natural immune system mistakenly attacking and damaging healthy, normal cells and tissue. Currently, an estimated 60 different autoimmune diseases affect between 5 and 8 percent of the U.S. population[1]; making it one of the largest disease burdens faced today.
Divided into two distinct categories, autoimmune diseases are typically classified as organ-specific or systemic autoimmune diseases. Systemic autoimmune diseases include systemic lupus erythematosus (SLE), rheumatoid arthritis, systemic sclerosis, and polymyositis; organ-specific autoimmune diseases include Hashimoto thyroiditis, Graves disease, type 1 insulin-dependent diabetes, and pernicious anemia.
Currently, most cases of autoimmune disease are treated with corticosteroids, cyclophosphamide, azathioprine, and/or methotrexate. While all of these medications have been demonstrated to be effective in treating autoimmune disease in some capacity, improvement is not universal; these medications have also been associated with known toxicities.
As research continues to explore the immune system and various autoimmune disorders, it appears that adult stem cells offer promise for effective, non-pharmacological treatment of autoimmune disease.
The author of this review points out that while many animal studies exploring the potential benefits of autologous and allogeneic hematopoietic stem cells (HSCT) exist, the danger associated with allogeneic bone marrow transplants has limited studying these transplants to only those subjects with severe autoimmune disorders that are not responding to other, more proven treatments.
The review also focuses on the treatment of autoimmune disease with mesenchymal stem cells (MSCs). Specifically, the author points to several in vitro studies demonstrating the immunomodulatory properties of MSCs as well as their immunosuppressive effects on MHC-mismatched lymphocyte proliferation. This form of MSC transplantation produces relatively short effects but has proven to be profoundly different from HSCT. Specifically, this procedure does not require the patient to be immunosuppressed in advance of transplantation and produces a therapeutic effect in the affected organ as a result of the homing of MSCs. Studies have demonstrated that MSC transplant has reversed multiorgan dysfunction in SLE mice and humans while also demonstrating stable 12 – 18-month disease remission. As a result, further clinical trials exploring autologous bone marrow MSC (BM-MSC) are currently ongoing.
With the difficulty and risk associated with BM-MSC transplantation, the author points out that since adipose tissue is readily available and easily obtainable, adipose tissue-derived MSC (AT-MSC) are being explored for their potential as a regenerative treatment and wound healing option. Early studies have demonstrated AT-MSC to have immunosuppressive properties that reduce experimental autoimmune encephalomyelitis (EAE), decrease spinal cord inflammation, and significantly ameliorate the severity of colitis and arthritis. In fact, there is convincing evidence indicating that AT-MSC transplant produces therapeutic results comparable to MSCs derived from bone marrow.
At the same time, gene therapy research exploring the use of stem cells as a vehicle in autoimmune disease demonstrated delivery of brain-derived neurotrophic factor (BDNF) genes in an animal model of multiple sclerosis using bone marrow stem cells and human insulin gene transfected BM-MSC therapy in murine type 1 insulin-dependent diabetes has demonstrated positive results, including decreased blood glucose level, improved secretion of human insulin in serum and liver, and delayed onset and clinical severity of EAE.
As research continues to explore the benefits of adult stem cell therapy for the treatment of autoimmune disease, and with genetic therapy showing promising treatment options, researchers are optimistic of the benefits provided through a combination of stem cell and gene therapy.
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