Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that causes irreversible damage to the alveoli and leads to pulmonary interstitial fibrosis. Patients with IPF often experience severe difficulty breathing, which can result in respiratory failure and death. The disease is challenging to diagnose, has a high mortality rate, and a median survival of only three to five years after diagnosis, which is worse than many forms of cancer.
Current treatments primarily focus on supportive care, such as lung transplantation, mechanical ventilation, and oxygen therapy. Drugs like pirfenidone and nintedanib can slow disease progression but do not repair damaged lung tissue. For this reason, researchers are exploring the use of mesenchymal stem cells (MSCs) as a potential new therapy for IPF. MSCs are multipotent stem cells capable of self-renewal, differentiation, and secreting a variety of factors that may reduce inflammation, promote tissue repair, and regulate immune responses.
As part of this review, Li et al. summarize recent studies on MSCs in reducing lung inflammation and fibrosis, highlighting their potential mechanisms, such as migration and differentiation, secretion of soluble factors and extracellular vesicles, and regulation of endogenous repair processes.
Pathological Changes in IPF
The main pathological features of IPF include widespread alveolar damage, excessive proliferation of fibroblasts, and deposition of extracellular matrix (ECM) proteins. Fibroblastic foci, areas of active fibroblast and myofibroblast accumulation, are a hallmark of the disease and strongly correlate with patient outcomes. Fibroblasts in these foci arise from three primary mechanisms: proliferation of resident fibroblasts, epithelial-mesenchymal transition (EMT), and bone marrow-derived fibrocytes.
Resident fibroblasts proliferate and differentiate into myofibroblasts under the influence of factors like transforming growth factor-β (TGF-β). Myofibroblasts produce collagen and other ECM proteins, which contribute to tissue stiffness and fibrosis. EMT occurs when alveolar epithelial cells lose epithelial markers and acquire mesenchymal traits, becoming fibroblast-like cells that contribute to ECM deposition. TGF-β is a key driver of EMT, acting through pathways such as Ras/ERK/MAPK signaling. Endothelial cells can also undergo a similar transition, producing collagen and contributing to fibrosis. Bone marrow-derived fibrocytes, circulating in the blood, migrate to damaged lung tissue and differentiate into fibroblasts. Their accumulation is linked to poor prognosis and is guided by chemokine signaling pathways like CXCL12/CXCR4 and CCL3/CCR5.
Properties of Mesenchymal Stem Cells
MSCs, first discovered in 1968, are multipotent cells that can differentiate into bone, cartilage, and fat. They can be sourced from bone marrow, adipose tissue, and umbilical cord blood, and are identified by fibroblast-like shape, plastic adherence, and surface markers (CD44, CD29, CD90) while lacking hematopoietic markers (CD45).
MSCs have low immunogenicity, can modulate the immune system, and support tissue repair. Transplantation in animal models of lung injury shows promise with minimal side effects, but human safety and efficacy remain uncertain due to species differences and small clinical trials. Potential risks include tumor formation and unwanted angiogenesis, especially in immunocompromised patients.
Mobilizing endogenous MSCs is also being studied, as these cells can migrate to injured tissue, secrete reparative factors, and aid repair, with agents like G-CSF enhancing mobilization, though outcomes vary.
Mechanisms of MSC Therapy in Pulmonary Fibrosis
Mesenchymal stem cells (MSCs) help repair lung injury through multiple, interconnected mechanisms: migration to injury sites, differentiation, secretion of bioactive factors, immune modulation, and regulation of lung defenses.
MSCs are guided to damaged lung areas by chemokines such as stromal cell-derived factor-1 (SDF-1) and interleukin-8 (CXCL8). Once at the injury site, they can differentiate into type II alveolar epithelial cells, supporting tissue repair. This differentiation is influenced by Wnt signaling pathways, though in some cases, MSCs may become fibroblast-like cells, which could worsen fibrosis.
A key part of MSC therapy is the secretome, a collection of soluble factors. Growth factors like KGF, HGF, EGF, Ang-1, and VEGF restore alveolar and endothelial function, maintain lung barrier integrity, and reduce fluid buildup. Anti-inflammatory molecules such as IL-1ra, IL-10, PGE2, and TSG-6 help control inflammation and promote repair. MSCs also encourage macrophages to shift from a pro-inflammatory (M1) to an anti-inflammatory (M2) state, aiding recovery. Early administration during acute inflammation provides the most benefit.
MSCs exert immunomodulatory effects by secreting chemokines, adhesion molecules, and regulatory factors like nitric oxide (NO) and indoleamine-2,3-dioxygenase (IDO), which suppress T-cell activity. They influence B cells and support regulatory T cells to maintain immune balance. MSCs can also secrete TGF-β, which can either aid healing or promote fibrosis depending on context and timing.
Extracellular vesicles (EVs), including exosomes and microvesicles, are another way MSCs deliver therapeutic benefits. They carry proteins, RNAs, and other molecules that reduce inflammation and promote tissue repair. EV-based therapy may offer many of the benefits of MSCs while minimizing risks associated with cell transplantation.
Finally, MSCs regulate molecules involved in oxidative stress, inflammation, and tissue repair. They decrease pro-fibrotic and inflammatory signals like matrix metalloproteinases and TGF-β1 while increasing antioxidant enzymes and repair-promoting proteins such as FoxM1, stanniocalcin, and Miro1, all of which protect lung tissue and combat fibrosis.
Advancing MSC Therapy for Pulmonary Fibrosis
Mesenchymal stem cell therapy represents a promising approach for treating idiopathic pulmonary fibrosis. Its benefits involve multiple mechanisms, including homing to injured tissue, differentiation, secretion of growth factors and cytokines, immunomodulation, and enhancement of endogenous lung defenses. MSCs are most effective when administered early in the inflammatory phase of lung injury, highlighting the importance of timing. Despite encouraging preclinical and early clinical results, safety and efficacy in humans remain under investigation, and some contradictory findings underscore the complexity of MSC therapy.
Li et al. conclude that future research should focus on optimizing MSC mobilization, improving therapeutic efficacy, exploring the role of microRNAs, and advancing clinical trials to establish MSC-based therapies as viable treatments for IPF.
Source: Li X, Yue S, Luo Z. Mesenchymal stem cells in idiopathic pulmonary fibrosis. Oncotarget. 2017 May 23;8(60):102600-102616. doi: 10.18632/oncotarget.18126. PMID: 29254275; PMCID: PMC5731985.
Living with a spinal cord injury changes how you move, feel, and function every day. You might be searching for more support in your recovery or looking into alternatives when other treatments have plateaued. At Stemedix, we provide access to regenerative medicine options, including stem cell therapy for spinal cord injury, designed to support your body’s healing potential. Our goal is to help you maintain independence and improve your quality of life through individualized care.
Stem cells for the treatment of spinal cord injury are being explored for their ability to support damaged nerve tissues and help reduce symptoms related to mobility, pain, and function. This therapy is not a cure, but it may serve as another layer of support in your recovery process. In this article, we will discuss how spinal cord injuries affect the body and how stem cell treatment may fit into your path forward.
Defining Spinal Cord Injury: Causes and Impact
A spinal cord injury doesn’t just affect mobility—it changes how the entire body communicates, functions, and adapts. Knowing how these injuries happen and what they cause can help you better plan your care and treatment options.
Common Causes of Spinal Cord Injury
A spinal cord injury is most often caused by sudden trauma or underlying medical conditions that disrupt nerve communication within the spine. These injuries commonly follow events such as vehicle crashes, major falls, sports-related impacts, or violent encounters.
Other cases develop from non-traumatic sources. These include conditions like spinal tumors, multiple sclerosis, and certain infections that interfere with the spinal cord’s structure and function. Degenerative diseases—such as spinal stenosis or arthritis—can also contribute to gradual nerve damage over time.
A spinal cord injury disrupts messages between the brain and the rest of the body. Where the injury occurs determines what parts of the body are affected. For example, if damage happens in the cervical spine, it can interfere with both arm and leg function. A lower injury in the lumbar region, by contrast, may impact only the hips and legs.
Immediate and Long-Term Effects on the Body
A spinal cord injury can result in paralysis, loss of sensation, and autonomic system dysfunction. Right after the injury, you might notice loss of movement, reduced feeling in certain areas, or changes in bladder and bowel control. These effects often appear quickly and may be temporary or permanent, depending on the severity.
As time passes, new challenges can appear. You may notice muscle weakness from disuse, skin breakdown from reduced movement, or respiratory changes if the injury is high enough to affect breathing muscles. Pressure injuries, also called pressure sores, and recurrent infections such as urinary tract infections are common secondary complications that require careful management. These long-term impacts highlight the importance of continuous support and well-structured care plans.
Classification of Spinal Cord Injuries by Severity and Location
Knowing where and how a spinal cord injury occurs helps you and your care team decide on the right approach to managing your recovery. The level and type of injury directly impact physical abilities, personal care needs, and long-term health planning.
Complete vs. Partial Injury Overview
A complete spinal cord injury causes total loss of motor and sensory function, while a partial injury retains some level of nerve signal transmission. If you’ve been diagnosed with a complete spinal cord injury, it means there’s no communication between the brain and the body below the injury site. This disconnect leads to full paralysis and loss of sensation below that point.
In contrast, partial, also called incomplete injuries, allow some signals to continue traveling along the spinal cord. You may notice that you still have some sensation, or you may be able to move certain muscles. These residual functions vary greatly between individuals. This classification matters because it plays a role in setting realistic goals for therapy and rehabilitation.
Differences Between Cervical, Thoracic, and Lumbar Injuries
The location of a spinal cord injury determines which parts of the body are affected. Cervical injuries often result in quadriplegia, thoracic injuries affect trunk and leg function, and lumbar injuries primarily impair lower limb control and bowel or bladder management.
Cervical injuries, those in the neck region, are often the most severe. They can impact movement and feeling in all four limbs, including breathing, swallowing, and arm function. These types are the most likely to require long-term assistive devices or full-time care.
Thoracic injuries occur in the middle section of the spine. While they typically spare arm movement, they may limit balance, torso strength, and control over abdominal muscles. It may be harder to sit upright or regulate body temperature below the injury level.
Lumbar injuries involve the lower spine and tend to affect the legs and lower body systems. Many people with lumbar-level injuries retain upper body function, but mobility challenges and changes in bladder or bowel function often follow. This type of injury may still allow for independent movement with the use of braces, walkers, or wheelchairs.
At Stemedix, we review all available medical records to understand your specific injury type and level before recommending any regenerative treatment option. This allows us to align our approach with your needs and current capabilities.
Stem Cell Therapy Explained: Purpose and Methods
Stem cell therapy for spinal cord injury involves introducing regenerative cells to promote repair and protect surviving tissue. These cells are introduced into areas near the injury site, where they may influence several healing processes. One of the primary actions is the regulation of the immune response, which helps reduce further damage caused by ongoing inflammation. In addition, stem cells may release biological signals that support the health of existing nerve cells and encourage the development of new connections within the nervous system.
Types of Stem Cells Used in Therapy
Stem cells for the treatment of spinal cord injury may sometimes include mesenchymal stem cells (MSCs), neural stem cells, and induced pluripotent stem cells (iPSCs). Each type works differently, but MSCs are the most frequently used in current therapeutic models. These cells are typically harvested from bone marrow or adipose (fat) tissue. They’re known for their ability to regulate inflammation and release molecules that promote healing.
Neural stem cells, on the other hand, are more specialized and are under investigation for their ability to integrate into damaged neural circuits. Induced pluripotent stem cells, adult cells reprogrammed into a more flexible, embryonic-like state, are still largely in the research phase. Although they offer broader potential, their use requires rigorous safety protocols to manage risks like tumor formation.
At Stemedix, we focus on therapies that use stem cells for the treatment of spinal cord injury with strong safety records and established handling procedures. Our team works closely with patients and referring physicians to coordinate care that is both informed by current science and centered on individual medical history.
Biological Actions of Stem Cells in Nerve Repair
Stem cells offer more than just cellular replacement—they create conditions in the body that support repair and healing. When applied to spinal cord injury, their effects can influence both immune activity and tissue regeneration.
Influence on Inflammation and Immune Response
Stem cells help regulate immune responses and reduce secondary damage from inflammation. After a spinal cord injury, inflammation can lead to further damage beyond the initial trauma. Immune cells flood the site, often destroying nearby healthy tissue in the process. This secondary damage can be just as limiting as the original injury.
Stem cells interact with this process by releasing bioactive molecules like cytokines and growth factors. These signals tell immune cells to calm their response and shift toward tissue support instead of attack.
This immune-modulating activity helps preserve nerve cells that might otherwise deteriorate. You’re not just adding cells—you’re also working with your body’s existing systems to limit further harm and stabilize the injury site.
Role in Regenerating Damaged Neural Tissue
Stem cell treatment for spinal cord injury may support the formation of new neural connections and repair mechanisms. Spinal cord damage disrupts the flow of signals between your brain and body.
To support repair, stem cells may promote three biological processes: axonal growth, remyelination, and cellular restoration. Axonal growth refers to the extension of nerve fibers that transmit signals. Without axons, communication between nerves stops.
Remyelination involves restoring the protective sheath around nerves, which allows electrical impulses to travel efficiently. In cases of spinal cord injury, this sheath often breaks down, leading to slower or blocked signals.
Studies show that certain types of stem cells, including induced pluripotent stem cells (iPSCs) and MSCs, can release growth factors that encourage axons to regrow and remyelinate existing nerves. These biological effects don’t occur all at once. They build over time as the cells interact with damaged tissue, guiding regeneration step by step.
At Stemedix, we focus on regenerative strategies that support your body’s efforts to recover. Stem cell therapy for spinal cord injury is structured to work with your body, using natural signaling processes to support healing at the cellular level.
Observed Outcomes from Stem Cell Treatments
Many individuals exploring regenerative options want to know what to expect from stem cell therapy. While results can differ, this section outlines some of the most reported effects based on real patient experiences and clinical data.
Enhancements in Mobility and Sensory Recovery
Some patients receiving stem cell treatment for spinal cord injury report improved strength, coordination, and sensation. These outcomes are often influenced by the level and completeness of the injury. For example, individuals with incomplete spinal cord injuries—where the spinal cord is damaged but not fully severed—have demonstrated positive changes in limb control, trunk stability, and tactile feedback following therapy.
Certain patients experienced measurable improvements in motor scores and sensory function within months after receiving stem cell injections. These functional changes, although not universal, suggest that the cells may support the body’s effort to reconnect or reinforce neural pathways.
The timing of intervention also plays a role. People who began stem cell treatment in the sub-acute phase (weeks after injury) have shown different patterns of recovery compared to those in chronic stages. It’s important to consider that early intervention may help maximize the biological environment for healing, but research is still ongoing to determine the full scope of response across timelines.
Reduction of Discomfort and Muscle-Related Symptoms
Stem cells have been observed to reduce spasticity and neuropathic pain associated with spinal cord injury. Spasticity, which causes involuntary muscle contractions, and nerve-related pain are among the most persistent challenges following spinal trauma. These symptoms can disrupt sleep, limit mobility, and interfere with rehabilitation.
Some patients who received mesenchymal stem cell (MSC) therapy reported decreased muscle stiffness and better pain control. Stem cell infusions modulated the immune response and contributed to reduced inflammation around damaged spinal segments. This shift may help explain why pain and tightness sometimes improve after treatment.
Relief from these symptoms can create opportunities for more active daily routines and improved engagement in physical therapy. While stem cell therapy is not a replacement for traditional pain management or rehabilitation, it may complement those approaches in supportive ways.
At Stemedix, we’ve seen that outcomes vary depending on the person’s overall health, injury characteristics, and treatment timing. Our role is to offer access to care designed around your condition while helping you understand how regenerative therapy might fit into your goals for living with a spinal cord injury.
The Treatment Process at Stemedix: Patient-Centered Approach
Every individual with a spinal cord injury presents a unique medical profile. At Stemedix, based in Saint Petersburg, FL, we align the treatment process with your personal health history and therapy goals to support your experience from evaluation through follow-up.
Importance of Diagnostic Information From Referring Physicians
Stemedix requires patients to provide medical imaging and records from their diagnosing physicians to determine eligibility for stem cell therapy. We rely on your existing records—such as MRIs, CT scans, and clinical summaries—to fully understand the scope of your spinal cord injury. This information gives us a starting point to evaluate whether stem cell therapy may be appropriate for your situation.
A detailed medical history helps our team determine the location and severity of your injury while also providing insight into how your body has responded to previous interventions. Accurate documentation from your physician allows us to move forward responsibly and reduce avoidable risks during the treatment process.
Tailoring Treatments to Individual Medical Histories
Each stem cell treatment for spinal cord injury is customized according to the patient’s health condition, injury level, and treatment goals. We look at a range of personal factors before planning treatment. These include the type of spinal cord injury you’ve experienced—whether complete or incomplete—as well as how long it has been since the initial trauma. Conditions like diabetes, autoimmune disorders, or chronic infections, as well as the medications you’re currently using, are all taken into account.
Administration Protocols and Safety Measures
Stemedix uses sterile, clinically guided protocols for administering stem cells. Each procedure is conducted in a controlled medical setting under the direction of trained clinicians. We use laboratory-tested biologics and sterile techniques to lower the risk of complications. All patients are closely observed before, during, and after the procedure.
Throughout treatment, we document patient responses, both for clinical records and to support communication with your existing care team. This consistent monitoring helps track progress and contributes to adjusting your care as needed over time. According to clinical studies, stem cell therapy has been associated with neurological improvements in some individuals with chronic spinal cord injuries, especially when introduced within a defined therapeutic window.
Patient Support Beyond Therapy
Recovery involves more than medical treatment alone. At Stemedix, we understand the physical and logistical challenges you may face when dealing with a spinal cord injury. That’s why we help coordinate accessible transportation and lodging for patients traveling from out of town, easing the burden of planning and focusing attention on your care.
To support your comfort during therapy, we provide access to mobility aids like wheelchairs and walkers, along with personal assistance when needed. Our team creates an accessible environment that allows you to move through treatment with as much comfort and independence as possible.
Start Your Recovery Journey with Stemedix Today
If you’re exploring advanced treatment options for spinal cord injury, our team at Stemedix is here to guide you every step of the way. We offer patient-focused care, treatment coordination, and support services designed around your individual needs. To learn more or speak with a care coordinator, call us at(727) 456-8968 or email yourjourney@stemedix.com.
Traumatic brain injury (TBI) is a major cause of disability worldwide, affecting over 50 million people each year. It can result from accidents, falls, sports injuries, or violent impacts. TBI can lead to immediate problems like loss of consciousness, confusion, and memory difficulties, and long-term consequences such as cognitive deficits, physical disabilities, speech challenges, and mood disorders.
In addition, TBI is associated with an increased risk of developing neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Traditional treatments focus on stabilizing patients and reducing immediate damage, but they rarely restore lost brain function or prevent chronic complications.
As part of this review, Zhang et al. outline the key pathological processes of (TBI) and the mechanisms by which mesenchymal stem cell (MSC) therapy may provide treatment. The authors also highlight current research progress, identify major limitations, and emphasize the promising potential of MSC-based approaches for TBI.
Complexity of Injury Mechanisms
TBI involves both primary and secondary injury mechanisms. Primary injury occurs at the time of trauma and involves direct mechanical damage to brain tissue. Secondary injury develops over hours to days and includes inflammation, oxidative stress, mitochondrial dysfunction, and neuronal apoptosis. These processes are partly driven by the disruption of the blood–brain barrier, allowing immune cells to enter the brain and trigger a persistent inflammatory response. Understanding these mechanisms is crucial because interventions during the secondary phase may reduce neuron death and improve recovery outcomes.
Consequences of TBI
Secondary injury after TBI can trigger widespread cellular and tissue damage. Inflammation, oxidative stress, and apoptosis disrupt brain function and can worsen physical and cognitive outcomes. Long-term consequences may include memory loss, reduced motor control, difficulty speaking, and emotional changes. Damage to neurons and supporting cells, such as astrocytes and microglia, contributes to these deficits. The adult brain has limited capacity to repair itself, which makes TBI particularly challenging to treat.
Promise of Mesenchymal Stromal Cell Therapy
MSCs are multipotent stem cells found in bone marrow, fat tissue, skeletal muscle, synovial membrane, and peripheral blood. They have the ability to self-renew, differentiate into multiple cell types, and migrate to sites of injury. MSCs offer potential treatment for TBI through multiple mechanisms. They promote healing not just by replacing damaged cells but also through paracrine signaling, the release of extracellular vesicles (EVs) such as exosomes, and direct cell–cell interactions. These vesicles carry proteins, RNA, and other molecules that cross the blood–brain barrier to reduce inflammation, stimulate neuron growth, and protect surviving brain cells. Clinical studies have shown that MSC therapy can improve motor and cognitive recovery in patients with neurological injuries, suggesting they are a promising regenerative therapy for TBI.
Targeting Mitochondrial Dysfunction
Mitochondria are the energy-producing organelles in cells, and damage to them is a major feature of secondary TBI injury. Dysfunctional mitochondria trigger oxidative stress, apoptosis, and energy deficits that worsen brain damage. MSCs can transfer healthy mitochondria to injured neurons and other cells through tunneling nanotubes, extracellular vesicles, and other mechanisms. This transfer restores cellular energy production, reduces inflammation, and prevents cell death. Mitochondrial transfer also regulates immune cells, shifting macrophages toward a healing, anti-inflammatory state. Research shows that this process improves neuron survival, angiogenesis, and overall functional recovery of brain tissue.
Combating Oxidative Stress
Excessive reactive oxygen species (ROS) produced after TBI can damage DNA, proteins, and cell membranes, leading to further cell death. MSCs counteract oxidative stress through multiple mechanisms. They enhance antioxidant activity, increase protective proteins like Bcl-2, and reduce harmful molecules. Exosomes from MSCs carry additional protective factors that restore ATP production and activate cell survival pathways. Studies in animal models show that MSCs and their exosomes help preserve neurons, reduce injury progression, and improve recovery, offering advantages over treatments that address only one aspect of oxidative damage.
Reducing Neuroinflammation
Neuroinflammation is a key driver of secondary injury in TBI. Damage to the blood–brain barrier allows immune cells to enter the brain, activating microglia and astrocytes. These glial cells release inflammatory cytokines such as IL-1, IL-6, and TNF-α, attracting more immune cells and extending inflammation from the acute to chronic phase. MSCs help regulate the inflammatory environment by releasing anti-inflammatory factors, promoting microglial polarization to the M2 healing phenotype, and reducing the infiltration of peripheral immune cells. Studies show that MSC therapy lowers levels of proinflammatory molecules, restores blood–brain barrier integrity, reduces cerebral edema, and improves motor and cognitive function. Combination treatments with drugs that enhance anti-inflammatory effects have shown even greater improvements.
Preventing Apoptosis and Supporting Neurons
Neuronal apoptosis is a hallmark of secondary TBI injury and contributes to long-term functional deficits. MSCs help prevent apoptosis by delivering neurotrophic factors, regulating pro- and anti-apoptotic proteins, and reducing caspase activation. Their exosomes protect neurons, preserve white matter, and support glial cells. MSCs also stimulate angiogenesis, providing oxygen and nutrients to surviving neurons, which further supports tissue repair. These effects collectively improve neuron survival, facilitate functional recovery, and help restore brain physiology.
Comparison with Traditional Therapies
Traditional TBI treatments, such as surgery, hypothermia, and medications, primarily aim to stabilize patients and manage symptoms. While these approaches are necessary to prevent immediate harm, they often do not repair damaged brain tissue or restore neurological function. MSC therapy offers a broader approach by targeting mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis. Unlike traditional therapies, MSCs promote tissue regeneration and functional recovery. However, challenges remain, including potential contamination during culture, immune responses, and the theoretical risk of promoting tumor growth. Proper sourcing, handling, and delivery of MSCs are critical to maximizing safety and effectiveness.
Future Directions and Clinical Potential
MSC therapy holds great promise for TBI treatment, but additional research is needed to optimize outcomes. Scientists are investigating the best sources of MSCs, ideal timing for administration, most effective delivery methods, and appropriate dosages. Genetically modified MSCs may enhance therapeutic potential, and exosome-based treatments could provide safer, cell-free alternatives. Combination therapies with pharmacological agents or physical interventions may further improve results. Ongoing preclinical and clinical trials will help determine how MSCs can best be used to repair brain tissue and restore function in TBI patients.
The Potential of MSC Therapy for Traumatic Brain Injury
Traumatic brain injury is a complex condition with high rates of long-term disability. Secondary injury mechanisms such as oxidative stress, neuroinflammation, mitochondrial dysfunction, and apoptosis contribute to the progression of brain damage. MSCs offer a multi-targeted approach to treatment by providing mitochondrial support, antioxidant protection, anti-inflammatory effects, and anti-apoptotic benefits. While challenges remain regarding safety, delivery, and standardization, MSCs and their exosomes represent a promising frontier in regenerative medicine.
With continued research and clinical development, Zhang et al. concluded that MSC therapy has the potential to improve neurological outcomes and quality of life for millions of patients worldwide.
Source: Zhang K, Jiang Y, Wang B, Li T, Shang D, Zhang X. Mesenchymal Stem Cell Therapy: A Potential Treatment Targeting Pathological Manifestations of Traumatic Brain Injury. Oxid Med Cell Longev. 2022 Jun 15;2022:4645021. doi: 10.1155/2022/4645021. PMID: 35757508; PMCID: PMC9217616.
Multiple sclerosis (MS) is a chronic disease that affects the central nervous system, disrupting the way the brain and spinal cord communicate with the rest of the body. Over the years, researchers have developed many treatments that have transformed the outlook for patients with relapsing-remitting MS (RRMS), the most common form of the disease. Unfortunately, these advances have not been as effective for people with progressive MS (PMS), a form of the condition where symptoms steadily worsen over time without clear periods of recovery.
For patients with PMS, there is still an urgent need for new therapies that do more than slow the disease. Treatments must protect the brain and spinal cord, calm harmful immune responses, and even help repair damage that has already been done. Researchers are exploring innovative ways to meet this challenge, and one of the most exciting possibilities lies in the use of neural stem cells.
In this review, Genchi et al. present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial.
Understanding Neural Stem Cells
Neural stem cells are special cells found in the brain and spinal cord. They can divide and create new cells, and they have the unique ability to develop into different types of brain cells, including neurons, astrocytes, and oligodendrocytes. These cells not only replace damaged tissue but also support the surrounding environment, release helpful molecules, and guide repair processes.
Early research once assumed that stem cell therapy worked only by replacing lost cells. Now, scientists know the story is much more complex. Neural stem cells can remain in an immature state and still have powerful effects. They can interact with the body’s own cells, regulate immune activity, and send out signals that protect nerves from further harm. This “bystander effect” is now seen as one of the most important ways stem cells may help patients with PMS.
The STEMS Clinical Trial
The STEMS trial was the first phase 1 study to test the safety of transplanting human fetal neural precursor cells (hfNPCs) into patients with progressive MS. The cells were delivered directly into the fluid surrounding the spinal cord, a method known as intrathecal injection.
The main goal was safety—primarily, if the treatment could be given without causing serious harm. At the same time, the authors explored whether the cells might show early signs of benefit, such as protecting brain volume or improving certain cognitive functions.
Safety Outcomes of the Trial
The results of this study were encouraging. Over a two-year follow-up period, the authors found no severe side effects directly linked to the transplanted cells were observed. Most side effects were mild or moderate, such as headaches or temporary discomfort.
One patient experienced a relapse of MS symptoms, but this was not thought to be caused by the stem cell therapy. Some patients developed new spots of inflammation on MRI scans, but these were considered part of the natural disease process rather than a direct result of the treatment. Importantly, no evidence suggested that the therapy caused dangerous or uncontrolled growth of cells in the nervous system.
Potential Benefits of Neural Stem Cell Therapy
Although the trial was small and not designed to prove effectiveness, Genchi et al. noticed several promising trends.
Slowing Brain Volume Loss
Brain shrinkage, also known as atrophy, is a hallmark of progressive MS and is strongly linked to worsening disability. In the trial, patients who received higher doses of stem cells showed a slower rate of brain and gray matter shrinkage over two years. This suggests the therapy may have a protective effect on the nervous system.
Cognitive Improvements
Another surprising finding was improvement in a test of processing speed, a measure of how quickly someone can understand and respond to information. While practice effects may have played a role, the fact that patients with worse baseline scores improved the most hints at a real therapeutic effect.
Biological Signals of Repair
Spinal fluid samples taken from patients showed higher levels of certain molecules linked to nerve protection, immune regulation, and tissue repair. For example, increases in growth factors such as GDNF and VEGF-C suggested that the transplanted cells were encouraging the nervous system to heal itself. Other changes hinted at reduced inflammation, which is critical in slowing progression of MS.
The Complex Picture of Inflammation
Not all findings were straightforward. Some patients developed new inflammatory spots on brain scans, even though they did not experience relapses. The authors could not find a clear link between the number of transplanted cells and the amount of new inflammation, but they caution that more work is needed to understand this pattern.
Interestingly, some molecules that are usually considered pro-inflammatory also play roles in nerve repair and stem cell activity. For instance, increases in IL-15 and GM-CSF could be seen as either harmful or helpful depending on context. This highlights how complex the immune system is in MS and why therapies must be carefully studied in larger groups of patients.
Limitations of the Study
While the findings are promising, it is important to keep in mind the limitations. The trial included only a small number of patients and did not have a control group for comparison. The follow-up period of two years may not be long enough to understand the full effects of stem cell therapy, especially since progressive MS changes slowly.
Measures of disability, such as the Expanded Disability Status Scale (EDSS), showed little change. However, this scale is not very sensitive in patients who already have significant disability, and the inclusion criteria may have created bias. Tests of hand function suggested mild worsening, though this was expected given the disease stage.
Significance for Progressive MS
Despite these challenges, the STEMS trial marks an important step forward. For the first time, the authors demonstrated neural stem cells to be safe and well-tolerated when transplanted into patients with PMS. Early signals suggest they may protect the brain, slow shrinkage, and create a more supportive environment for repair.
Progressive MS is notoriously difficult to treat because it involves ongoing nerve loss and scarring, not just inflammation. By targeting multiple processes at once—immunomodulation, neuroprotection, and regeneration—stem cells may offer something no current therapy can.
Looking Ahead: Next Steps in Research
According to the authors, the next step is larger clinical trials that test the therapy in more patients and include control groups for comparison. Researchers will also need to refine dosing, understand how long the transplanted cells survive, and determine whether benefits can be sustained over many years.
Future studies may explore combining stem cell therapy with existing MS treatments to maximize effectiveness. Scientists also hope to learn whether neural stem cells can not only protect the brain but also restore lost function, offering real improvements in quality of life.
A Cautious but Hopeful Outlook
For now, patients with progressive MS should view neural stem cell therapy as an experimental but hopeful avenue. While it is too early to say whether it will become a standard treatment, the early signs suggest that it has the potential to slow progression and improve aspects of brain health.
The STEMS trial demonstrates the importance of moving beyond symptom management and exploring treatments that directly target the mechanisms of neurodegeneration. Neural stem cells could represent a powerful new tool in the fight against progressive MS, but much more research is needed.
Source: Genchi A, Brambilla E, Sangalli F, Radaelli M, Bacigaluppi M, Furlan R, Andolfo A, Drago D, Magagnotti C, Scotti GM, Greco R, Vezzulli P, Ottoboni L, Bonopane M, Capilupo D, Ruffini F, Belotti D, Cabiati B, Cesana S, Matera G, Leocani L, Martinelli V, Moiola L, Vago L, Panina-Bordignon P, Falini A, Ciceri F, Uglietti A, Sormani MP, Comi G, Battaglia MA, Rocca MA, Storelli L, Pagani E, Gaipa G, Martino G. Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study. Nat Med. 2023 Jan;29(1):75-85. doi: 10.1038/s41591-022-02097-3. Epub 2023 Jan 9. PMID: 36624312; PMCID: PMC9873560.
Degenerative disc disease (DDD) is one of the most common causes of chronic low back pain. It happens when the spinal discs, which act like cushions between the bones of the spine, begin to wear down over time. This process is often part of normal aging, but it can also be influenced by genetics, lifestyle, injuries, and overall health.
As the discs degenerate, they lose their ability to absorb shock. This can lead to pain, stiffness, and in some cases, additional spinal conditions such as herniated discs, spinal stenosis, or instability between vertebrae. People living with DDD often experience pain that limits daily activities, disrupts sleep, and decreases overall quality of life.
Conventional treatments for DDD usually begin with conservative approaches, such as physical therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), chiropractic care, or acupuncture. For patients whose pain does not improve, surgery may be considered. Surgical options include procedures like spinal fusion or disc replacement. While these approaches can offer short-term relief, they often do not stop the progression of degeneration, and some patients continue to experience pain in the long run.
Because of these challenges, researchers have been looking into new ways to slow or even reverse the disc degeneration process. One of the most promising areas of research involves the use of stem cells—specifically mesenchymal stem cells (MSCs).
As part of this study, Xie et al. evaluate the clinical efficacy and safety of MSC transplantation in patients with DDD.
Why Stem Cells Are Being Studied for DDD
Stem cells are special cells that can develop into many different cell types in the body. Mesenchymal stem cells, or MSCs, are found in bone marrow, adipose tissue, and other areas. They have unique properties that make them attractive for treating degenerative conditions.
MSCs can reduce inflammation, support tissue repair, and even help create new structural material for damaged tissues. In the case of DDD, researchers believe that MSCs could help regenerate spinal discs by:
Reducing inflammation inside the disc
Stimulating the production of new, healthy disc tissue
Improving hydration of the disc, which helps maintain its cushioning ability
Animal studies have shown encouraging results, suggesting that MSC therapy could help preserve disc structure and function. Some early human studies have also suggested potential benefits. However, until recently, clinical evidence was limited and sometimes inconsistent.
To better understand whether MSCs are effective for DDD, the authors of this study performed a meta-analysis—an analysis that combines results from multiple studies to look at the bigger picture.
What the Meta-Analysis Looked At
This study by Xie et al. reviewed randomized controlled trials (RCTs), which are considered one of the most reliable types of clinical research. The researchers looked at trials that compared MSC treatment to standard care or control groups in patients with degenerative disc disease.
They evaluated two main outcomes:
Pain reduction, measured with the Visual Analog Scale (VAS). This tool asks patients to rate their pain on a scale from 0 (no pain) to 10 (worst possible pain).
Functional improvement, measured with the Oswestry Disability Index (ODI). This questionnaire looks at how back pain affects everyday activities like sitting, walking, sleeping, lifting, and social life.
They also reviewed safety outcomes, including whether MSC treatments led to more adverse events compared to control groups.
By combining results from multiple studies, the meta-analysis aimed to answer two important questions:
Does MSC therapy improve pain and function for patients with DDD?
Is MSC therapy safe?
How MSC Therapy Affects Pain
The results of the pooled analysis showed that MSC therapy was associated with significant reductions in pain scores. Patients who received MSC treatment reported lower VAS scores compared to those who did not.
When the authors looked at different time points, they found that MSC therapy reduced pain at 3 months, 6 months, 12 months, and even beyond 24 months. This suggests that the benefits are not just short-term but may continue over time.
Another way the authors measured results was by looking at how many patients achieved “clinically meaningful” pain relief. This means the improvement was large enough to make a real difference in daily life, not just a small statistical change. They found that a higher percentage of MSC-treated patients reached these meaningful improvements compared to control patients.
According to Xie et al., this demonstrates that MSC therapy doesn’t just lower average pain scores on paper—it helps more patients experience relief they can feel.
How MSC Therapy Affects Function
Pain relief is important, but for people with DDD, regaining function is just as critical. The meta-analysis showed that MSC therapy also improved ODI scores, meaning patients could perform daily activities with less difficulty.
The improvements were especially noticeable in longer-term follow-up, at 24 months or more. While shorter-term results (3, 6, and 12 months) showed trends toward improvement, the most significant functional gains appeared over time. This suggests that MSC therapy may take time to have its full effect, as the cells work to repair and stabilize the damaged disc environment.
Like with pain, more patients in the MSC groups achieved meaningful improvements in function compared to those receiving other treatments.
Safety of MSC Therapy
Safety is always a concern with new therapies. MSCs are generally considered low-risk because they do not trigger strong immune responses. In the studies included in this analysis, most patients tolerated MSC therapy well.
The most commonly reported side effects were back pain, joint pain, or muscle spasms—symptoms that were not significantly different between MSC and control groups. However, there was a small but statistically significant increase in treatment-related side effects in the MSC groups. Importantly, serious adverse events were rare and not significantly different between groups.
This means that while MSC therapy appears relatively safe, careful monitoring is still important, and more research is needed to fully understand potential risks.
Clinical Implications for Patients
The results of this meta-analysis suggest that mesenchymal stem cell therapy could offer meaningful benefits for people living with degenerative disc disease. Patients who received MSCs reported:
Reduced back pain over both short- and long-term follow-up
Improved ability to perform daily activities
Relief that was more likely to reach clinically important levels
At the same time, the therapy appeared generally safe, with no major differences in serious adverse events compared to standard treatments.
According to the authors, this makes MSC therapy a promising option for patients who have not found relief through conservative measures and want to avoid or delay surgery. However, it is important to remember that MSC treatment for DDD is still being studied. More large, high-quality clinical trials are needed to answer key questions, such as:
What is the best source of MSCs (bone marrow, fat tissue, or others)?
How many cells are needed for optimal results?
How often should treatments be repeated?
Which patients are most likely to benefit?
Until these questions are answered, MSC therapy should be considered experimental, though the evidence so far is encouraging.
Limitations of the Research
While the meta-analysis strengthens the case for MSC therapy, there are some limitations to keep in mind. The number of studies and patients included was relatively small. Some studies showed inconsistent results, and not all measured outcomes the same way.
In addition, the quality of MSC preparations can vary depending on how cells are collected, processed, and stored. Differences in patient age, health status, and stage of disc degeneration may also affect results.
These factors mean that while the findings are promising, they should be interpreted cautiously until more research is available.
The Future of MSC Therapy for DDD
Research on stem cells and regenerative medicine is moving quickly. MSC therapy represents one of the most exciting frontiers in treating degenerative disc disease because it targets the underlying cause of the condition rather than just managing symptoms.
If ongoing studies continue to show positive results, MSC therapy could become a standard treatment option in the future. It has the potential to provide long-lasting pain relief, restore function, and possibly even slow or reverse the disc degeneration process.
For now, patients interested in stem cell therapy should consult with a qualified healthcare provider to learn whether they may be a candidate for clinical trials or specialized regenerative medicine programs.
As research continues, the authors believe that MSC therapy may become an important option for patients with chronic back pain caused by disc degeneration, helping them move beyond symptom management toward true disc repair and long-term relief.
Source: Xie B, Chen S, Xu Y, Han W, Hu R, Chen M, He R, Ding S. Clinical Efficacy and Safety of Human Mesenchymal Stem Cell Therapy for Degenerative Disc Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Stem Cells Int. 2021 Sep 13;2021:9149315. doi: 10.1155/2021/9149315. PMID: 34557231; PMCID: PMC8455197.
Rheumatic diseases are a broad group of chronic conditions that affect the joints, muscles, bones, ligaments, and sometimes internal organs. They are usually the result of a malfunctioning immune system that attacks healthy tissues. This leads to inflammation, pain, stiffness, and, in some cases, permanent organ damage. Common conditions in this group include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), osteoarthritis (OA), ankylosing spondylitis (AS), and osteoporosis (OP).
These illnesses can significantly reduce a person’s quality of life. Many people face persistent pain, fatigue, and reduced mobility, as well as the emotional challenges of living with a lifelong condition. While current treatments such as anti-inflammatory drugs, immunosuppressants, and biologic medications help manage symptoms, they do not cure the disease. They also come with risks of side effects and may not provide enough relief for everyone.
As part of this review, Hetta et al. summarize the clinical progress of MSC therapy in rheumatic diseases, highlight key findings from preclinical and clinical studies, and discuss challenges and future directions.
Role of Mesenchymal Stem Cell Therapy in Rheumatic Disease Management
Stem cells are unique because they can renew themselves and develop into many different types of cells. Mesenchymal stem cells, or MSCs, are a type of adult stem cell that can be found in bone marrow, fat tissue, umbilical cord blood, and even skin.
MSCs are particularly interesting to researchers because they can transform into bone, cartilage, and adipose cells. They also release natural substances that reduce inflammation, calm the immune system, and support healing. These qualities make them an appealing option for treating autoimmune and inflammatory diseases such as rheumatic conditions.
Why MSCs May Help Rheumatic Diseases
In rheumatic diseases, the immune system mistakenly attacks the body’s own tissues. This sets off cycles of inflammation and damage. MSCs may help by calming the overactive immune response, encouraging the growth of protective immune cells, and releasing growth factors that repair damaged tissues.
Rather than only masking symptoms, MSC therapy aims to restore balance to the immune system and support long-term improvement. This is why it has attracted so much attention in both laboratory research and clinical trials.
Promising Results Across Rheumatic Diseases
According to the authors, research into mesenchymal stem cells (MSCs) has shown encouraging results across a variety of rheumatic diseases where current treatments often fall short. Specifically:
In lupus, MSCs appear to calm harmful immune cells, promote regulatory ones, and reduce kidney inflammation, with early trials showing improvement in patients resistant to standard drugs.
In rheumatoid arthritis, studies suggest MSCs can lower inflammatory signals, protect cartilage, and ease symptoms, particularly in severe cases. Ankylosing spondylitis, which mainly affects the spine, may also benefit from MSC therapy, as both animal and small human studies indicate reduced inflammation and pain.
For osteoarthritis, MSCs may help repair cartilage and ease joint pain, with clinical trials reporting improved function in the knees and hips.
Osteoporosis research shows MSCs may encourage bone-building cells and inhibit bone breakdown, with exosome-based approaches offering a potential “cell-free” treatment.
In systemic sclerosis, MSCs have been linked to reduced scarring and improved skin and organ function.
In rare muscle disorders like dermatomyositis and polymyositis, early studies suggest gains in muscle strength and healing where conventional therapies have failed.
Together, these findings highlight MSCs as a promising new approach across a wide spectrum of autoimmune and degenerative conditions, though more large-scale and long-term studies are needed.
Ongoing Challenges and Emerging Strategies in MSC Therapy
Despite encouraging progress, MSC therapy still faces challenges. Hetta et al. report that results are not consistent, and not every patient responds the same way. The source of MSCs, the number of cells given, and the method of delivery can all affect outcomes.
Another challenge highlighted by the authors is standardization. To move MSC therapy into widespread use, researchers need to agree on best practices for collecting, preparing, and administering these cells.
Future approaches may involve combining MSC therapy with existing medications, engineering MSCs to work more effectively, or using MSC-derived exosomes as a safer alternative to full cell transplantation.
Therapeutic Promise and Future Outlook for Rheumatic Diseases
Mesenchymal stem cells represent one of the most exciting possibilities for treating rheumatic diseases. Research so far shows potential benefits for conditions such as lupus, rheumatoid arthritis, osteoarthritis, osteoporosis, systemic sclerosis, ankylosing spondylitis, and inflammatory muscle diseases. Unlike traditional medications that only ease symptoms, MSCs may help restore immune balance and encourage tissue repair.
While more research is needed to understand the long-term effects and best methods, MSC therapy offers real hope to millions of people living with painful and disabling conditions. With continued progress, the authors believe that it may one day change the way these chronic diseases are treated and give patients new opportunities for healing and improved quality of life.
Source: Hetta HF, Elsaghir A, Sijercic VC, Ahmed AK, Gad SA, Zeleke MS, Alanazi FE, Ramadan YN. Clinical Progress in Mesenchymal Stem Cell Therapy: A Focus on Rheumatic Diseases. Immun Inflamm Dis. 2025 May;13(5):e70189. doi: 10.1002/iid3.70189. PMID: 40353645; PMCID: PMC12067559.
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