by admin | May 15, 2025 | Mesenchymal Stem Cells, Neurodegenerative Diseases, Parkinson's Disease, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
Parkinson’s disease (PD) is a common, progressive neurological disorder that primarily affects movement. It occurs when brain cells that produce a chemical called dopamine begin to die, particularly in a part of the brain called the substantia nigra. Dopamine plays a crucial role in controlling movement, so when these cells are lost, people experience symptoms such as tremors, stiffness, slow movements, and trouble with balance.
While there are medications that help control symptoms, these treatments don’t stop the disease from progressing. Over time, their effectiveness may wear off, and they can cause unpleasant side effects. This has led scientists to explore new options – one of the most promising being stem cell therapy. This blog explores how stem cells might help treat Parkinson’s, what types of stem cells are being studied, and what we can expect in the near future.
The Challenge of Treating Parkinson’s Disease
Current treatments for PD mainly focus on managing symptoms, not curing the disease. The most commonly used drug is levodopa, which the body converts into dopamine. While levodopa helps relieve movement symptoms, it doesn’t only act where it’s needed. It floods the brain more broadly, which can lead to unwanted effects like hallucinations, cognitive problems, and involuntary movements (called dyskinesias).
Also, as the disease progresses, people often experience “motor fluctuations,” where the medication wears off before the next dose is due, making symptoms come and go unpredictably. More advanced therapies, such as deep brain stimulation or special levodopa gels, can help some people, but they’re not suitable or affordable for everyone.
In short, while medications help many people live better with Parkinson’s, they don’t solve the underlying problem: the loss of dopamine-producing cells. This is where regenerative medicine – and especially stem cells – comes in.
The Promise of Stem Cells in Parkinson’s Treatment
Stem cells are special cells that can turn into many different types of cells in the body. Importantly, they can also replicate themselves, giving researchers a potentially endless supply of cells to work with. For Parkinson’s, the idea is to turn stem cells into dopamine-producing neurons (the kind that die off in PD) and then implant them into the brain. Ideally, these new cells would settle into the right areas and start working like the original ones did – releasing dopamine in a natural, balanced way.
This targeted, biological approach might avoid many of the side effects of current drug treatments. It also holds the potential for long-lasting effects, possibly even slowing or stopping disease progression. Over the years, researchers have experimented with different kinds of cells to achieve this goal, but stem cells are currently the most promising option.
Types of Stem Cells Being Studied
Embryonic Stem Cells (ESCs)
These stem cells come from early-stage embryos (usually donated from in vitro fertilization). They can become any cell type in the body. Scientists have worked for years to coax these cells into becoming the specific type of dopamine-producing neurons lost in Parkinson’s. Early versions of this approach had inconsistent results – sometimes the cells didn’t fully become the right type of neuron, or the process produced too few usable cells.
However, advances in understanding how brain cells develop during embryonic stages have helped improve these techniques. Scientists now have better protocols that consistently produce authentic dopaminergic neurons – the ones from the midbrain region involved in movement control.
Even though results are getting better, some challenges remain. ESC-based treatments require immunosuppression, because the implanted cells aren’t from the patient’s own body and could be rejected. But despite these hurdles, clinical trials using ESC-derived neurons are expected to begin soon, marking a significant step forward.
Induced Pluripotent Stem Cells (iPSCs)
Introduced in 2007, iPSCs offer an exciting alternative. These are adult cells (like skin or blood cells) that scientists reprogram to become stem cells. Like ESCs, iPSCs can turn into almost any cell type, including dopamine-producing neurons.
One major advantage of iPSCs is that they can be made from a person’s own cells. This opens the door for personalized treatment – using your own cells to create brain implants – reducing the risk of immune rejection and the need for long-term immunosuppressive drugs.
So far, iPSC-based therapies have shown promise in animal studies, including in primates. Grafted cells survived, didn’t form tumors, extended connections to the brain’s movement centers, and improved movement symptoms. As with ESCs, human trials using iPSC-derived neurons are expected to begin soon.
Mesenchymal Stem Cells (MSCs)
MSCs come from adult tissues such as bone marrow. They’re easier to obtain than ESCs or iPSCs and don’t raise the same ethical concerns. However, they don’t naturally become dopamine-producing neurons. While they can produce some dopamine-related proteins in the lab, they don’t fully develop into the authentic neuron types needed for Parkinson’s treatment.
Still, MSCs may have other benefits. They release factors that reduce inflammation and protect brain cells from damage. These properties could help slow down disease progression or support other treatments, but so far, they haven’t been shown to improve movement symptoms directly. More research is needed to determine their role in PD therapy.
Induced Neurons (iNs)
Another approach is to directly convert a person’s regular body cells (like skin cells) into neurons without going through a stem cell stage. This avoids the risk of the cells turning into tumors, which is a theoretical concern with stem cells. These so-called induced neurons could also be made from a patient’s own cells.
Unfortunately, this method is still in its early days. The process doesn’t produce many cells, and results have been inconsistent. Right now, it’s not seen as a practical option for widespread treatment, but researchers are exploring ways to improve the technique.
There’s also some interest in trying this direct conversion inside the brain – turning support cells (astrocytes) into neurons in the patient’s brain itself. While intriguing, this concept is still highly experimental.
Progress in Stem Cell Research for Parkinson’s
The journey toward stem cell therapy for Parkinson’s has taken decades, but recent discoveries have helped clear many of the obstacles that held progress back. For instance, researchers now understand better how to guide stem cells into becoming the exact type of neurons needed for treatment. They’ve also developed quality control markers to ensure the cells being implanted are the right kind and at the right stage of development.
Animal studies have shown that these therapies can be safe and effective, leading to improvements in motor function without serious side effects. We’re now at the point where human trials using both ESCs and iPSCs are about to begin or are already in progress. These trials will help answer important questions about safety, effectiveness, and long-term outcomes.
Stem Cell Therapy: A Promising Future for Parkinson’s Treatment
Stem cell therapy is not a guaranteed cure for Parkinson’s disease, but it stands out as one of the most promising advancements in the effort to combat this debilitating condition. If successful, these therapies could offer more natural dopamine delivery, helping to reduce the side effects commonly associated with current medications. They may also provide longer-lasting benefits, potentially minimizing the need for frequent doses. By using a patient’s own cells, the treatments could be tailored for personalized care, and perhaps most significantly, they may introduce a new way to slow the progression of the disease rather than simply masking its symptoms.
There’s still significant work ahead. Clinical trials take time, and important questions remain about cost, access, and how to manufacture these treatments on a large scale. Even so, science continues to move forward at a rapid pace, and growing optimism can be felt throughout the medical community.
Parkinson’s disease remains a major challenge for patients, their families, and healthcare providers. While traditional medications can offer some relief, they do not offer a cure. As stem cell research accelerates, we may be moving closer to a future in which therapies don’t just manage symptoms – but help restore lost function and improve quality of life.
Source: Stoker TB. Stem Cell Treatments for Parkinson’s Disease. In: Stoker TB, Greenland JC, editors. Parkinson’s Disease: Pathogenesis and Clinical Aspects [Internet]. Brisbane (AU): Codon Publications; 2018 Dec 21. Chapter 9. Available from: https://www.ncbi.nlm.nih.gov/books/NBK536728/ doi: 10.15586/codonpublications.par
by admin | Apr 29, 2025 | Mesenchymal Stem Cells, Osteoarthritis, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy, Umbilical Stem Cell
Knee osteoarthritis (OA) is a long-term condition that affects millions of people worldwide. It occurs when the cartilage in the knee begins to break down, often due to aging, injury, or repeated stress on the joint. Early signs of OA include swelling, stiffness, and pain in the knee. Over time, the condition worsens, leading to a narrowing of the space between bones, the development of bony growths (osteophytes), and reduced joint mobility. This progression can significantly impact a person’s quality of life, especially in older adults.
One of the major challenges in treating knee OA is the poor ability of cartilage to repair itself. Cartilage lacks blood vessels and relies on nearby joint fluid and surrounding tissues for nutrients, making it especially vulnerable to damage. As a result, finding effective ways to heal or regenerate damaged cartilage has been a major focus of research in recent years.
In this review, Zhang et al. summarize the basic research and clinical studies to promote inflammatory chondrogenesis in the treatment of OA and provide a theoretical basis for clinical treatment.
The Role of Stem Cells in Cartilage Repair
Researchers have explored several treatment options for OA, including injections of corticosteroids, platelet-rich plasma, sodium hyaluronate, and more recently, stem cells. Among the various stem cell types being studied, human umbilical cord mesenchymal stem cells (HUC-MSCs) have shown promising results.
HUC-MSCs are a type of stem cell collected from the umbilical cords of newborns. These cells are especially attractive for medical use because they are easy to obtain, do not cause pain or harm to the donor, and are free from the ethical concerns that sometimes surround embryonic stem cells. They have also demonstrated the ability to multiply, change into different cell types (including cartilage cells), and regulate inflammation in the body.
Biological Benefits of HUC-MSCs in OA Treatment
According to the authors, what sets HUC-MSCs apart is their ability to both repair cartilage and control the inflammatory processes that worsen OA. These cells release helpful substances like cytokines, growth factors, and extracellular vesicles that support cartilage repair and reduce joint inflammation. HUC-MSCs can also develop into chondrocytes – cells that produce and maintain healthy cartilage.
In studies comparing HUC-MSCs to bone marrow-derived stem cells, HUC-MSCs have shown a higher potential for cartilage formation and a lower tendency to become fat or bone cells. These qualities make them a strong candidate for regenerating joint cartilage in OA patients. Additionally, the extracellular matrix (ECM) they produce is rich in type II collagen, which is essential for building strong, healthy cartilage.
Another biological benefit of HUC-MSCs is their ability to function well in low-oxygen environments, such as the interior of a joint. This makes them well suited for surviving and thriving in the harsh conditions of damaged knee joints. They also produce anti-inflammatory proteins like IL-10 and TGF-β1, which help reduce pain and inflammation, making the joint environment more suitable for healing.
Clinical Use of HUC-MSCs and Evidence of Effectiveness
Over the past decade, HUC-MSCs have been tested in laboratory studies, animal models, and human clinical trials. Results consistently show that these cells can improve symptoms, protect joint structures, and possibly slow the progression of OA.
In animal models of OA, researchers found that injecting HUC-MSCs into the knee joint helped reduce cartilage breakdown and cell death. In these studies, both single and repeated injections produced similar benefits, including better cartilage matrix production and less joint degeneration.
In human trials, HUC-MSCs have been tested in patients with moderate to severe OA. Results show improved joint function, reduced pain, and even signs of new cartilage formation on imaging studies. When compared to traditional treatments like sodium hyaluronate injections, HUC-MSC therapy has been shown to offer faster, longer-lasting relief and more meaningful improvements in joint health.
Additionally, treatment with HUC-MSCs has proven to be well tolerated and safe, with no serious side effects reported. Minor discomfort after the injection was typically short-lived and did not require medical intervention.
Mechanisms of Action and How HUC-MSCs Promote Healing
Zhang et al. found that HUC-MSCs help reduce the harmful effects of OA in several ways. First, they lower levels of inflammatory molecules like IL-1β, TNF-α, and IL-6 that are commonly found in arthritic joints. These substances are responsible for breaking down cartilage and increasing pain. HUC-MSCs also block enzymes such as MMP-13 and ADAMTS-5, which are known to degrade the cartilage structure.
At the same time, HUC-MSCs boost the production of cartilage-supporting proteins like collagen type II, aggrecan, and SOX9. These proteins are critical for rebuilding and maintaining the smooth, elastic tissue that cushions the ends of bones in the joint.
In addition to their anti-inflammatory and regenerative properties, HUC-MSCs influence the immune system by shifting inflammatory cells from a damaging state to a healing state. This shift helps calm the immune response within the joint and supports the repair process.
Several key cell signaling pathways – such as PI3K/Akt, mTOR, and Notch – are involved in this regenerative process. These pathways help control cell survival, growth, and the formation of new cartilage. As researchers continue to uncover how these pathways work, the authors anticipate new possibilities for targeted therapies will emerge.
Advantages Over Traditional and Other Stem Cell Treatments
Compared to other types of stem cells, such as those taken from bone marrow or fat tissue, HUC-MSCs offer multiple advantages. They are more readily available, easier to collect, and carry less risk of causing an unwanted immune response. They also multiply faster, have a greater capacity to form cartilage, and are less likely to develop into bone or fat cells – features that are particularly important when the goal is to repair joint cartilage.
Unlike treatments that simply reduce symptoms, such as painkillers or steroid injections, HUC-MSC therapy has the potential to address the root cause of OA by rebuilding damaged cartilage and rebalancing the joint’s internal environment.
Because of these advantages, the authors believe HUC-MSCs may represent a major step forward in the treatment of OA, especially for patients who have not responded well to traditional therapies or who are looking for a regenerative option before considering surgery.
A Promising Path Forward for Osteoarthritis Care
Human umbilical cord mesenchymal stem cells offer a new and exciting option for patients with knee osteoarthritis. With their ability to reduce inflammation, promote cartilage repair, and restore joint function, HUC-MSCs are rapidly becoming an important focus in regenerative medicine. As more research is conducted and the science behind these cells becomes clearer, they may soon become a standard part of OA treatment, offering hope for millions of people living with joint pain and stiffness.
Zhang P, Dong B, Yuan P, Li X. Human umbilical cord mesenchymal stem cells promoting knee joint chondrogenesis for the treatment of knee osteoarthritis: a systematic review. J Orthop Surg Res. 2023 Aug 29;18(1):639. doi: 10.1186/s13018-023-04131-7. PMID: 37644595; PMCID: PMC10466768.
by admin | Apr 24, 2025 | Lupus, Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
Systemic lupus erythematosus (SLE) is a complex autoimmune disease that can damage many different parts of the body, including the kidneys, lungs, brain, and blood system. Because it can attack so many organs, it often leads to serious illness and even death.
For many years, doctors have used medications like corticosteroids, cyclophosphamide (CTX), and mycophenolate mofetil (MMF) to control the disease. These treatments have helped patients live longer and have reduced the chances of severe organ failure. However, even with these medications, controlling SLE can still be very difficult for some patients.
Researchers have also developed newer drugs that target specific parts of the immune system, such as rituximab, belimumab, and tocilizumab, among others. While these drugs have improved outcomes for many people, they can sometimes cause serious side effects or lead to the disease coming back once the medication is stopped. Because of these challenges, scientists have been searching for new ways to treat SLE, and one promising option is stem cell therapy.
As part of this review, Yuan et al. explore how stem cells are being used to treat lupus, including the different types of stem cells, the challenges involved, and what the future of treatment may hold.
Hematopoietic Stem Cells and Their Role in Lupus Treatment
Hematopoietic stem cells (HSCs) are the type of stem cells that create all other blood cells. First discovered in 1961, HSCs have become important in treating both blood cancers and autoimmune diseases. In 1997, doctors began using HSC transplants (HSCT) to treat patients with both blood cancers and autoimmune diseases. The results demonstrated that not only did the cancers improve, but the autoimmune symptoms also got better.
Since then, many studies around the world have tested HSCT in people with SLE, and the results have been very encouraging – with patients even showing signs of what researchers call a “fundamental cure,” meaning their disease improved dramatically over the long term.
How Lupus Affects Stem Cells
SLE itself can harm the body’s natural stem cells. Research has shown that people with lupus have lower levels of circulating HSCs and endothelial progenitor cells (which help repair blood vessels). This loss of stem cells may be caused by an increase in programmed cell death, known as apoptosis. As a result, lupus patients may have a harder time repairing blood vessels, leading to problems like atherosclerosis (hardening of the arteries).
Other studies have found that certain changes in the immune system can make stem cells more likely to die off. For example, increased activity in a pathway called mTOR has been linked to poor blood cell production in mice with autoimmune diseases. However, research has also shown the opposite, with lupus conditions causing an increase in stem cells that behave abnormally.
Because of these differences, the authors indicate the need for further research to fully understand how lupus affects stem cells.
Comparing Hematopoietic and Mesenchymal Stem Cells
Because of the challenges with hematopoietic stem cells, researchers have also explored using mesenchymal stem cells (MSCs). MSCs come from bone marrow, fat tissue, or umbilical cord blood, and they have powerful anti-inflammatory and immune-regulating effects.
Clinical studies have shown that about 60% of patients responded well to the treatment, and there were very few serious side effects. This finding opened the door to a whole new field of lupus treatment research.
One significant difference between HSCT and MSC therapy is that MSCs do not require the intense and risky immune system wipe-out that HSCT does. Instead, MSCs can be infused into the body and work to rebalance the immune system naturally. Because of this, MSC therapy is generally safer, has fewer complications, and is more affordable than HSCT.
Another reason MSCs are so promising is that bone marrow MSCs from lupus patients often show structural and functional abnormalities, which means that transplanting healthy MSCs from a donor could help correct some of the immune system issues at the root of the disease.
Animal studies have strongly supported the effectiveness of MSCs in treating lupus, and early clinical trials in humans have shown encouraging results. Phase I and II studies suggest that MSC therapy is both safe and effective for SLE patients, but further larger clinical trials are needed to confirm these findings and to better understand exactly how MSCs help heal the immune system.
The Future of Stem Cell Therapy for Lupus
Stem cell therapy offers exciting new possibilities for patients with SLE who have not had success with traditional treatments. Hematopoietic stem cell transplants have been shown to help many patients, sometimes even achieving long-term remission. However, because of the high risks and costs involved, HSCT is likely to remain a treatment reserved for the most severe and treatment-resistant cases.
Mesenchymal stem cell therapy, on the other hand, appears to offer a safer, more accessible option that could benefit a much larger number of patients. With fewer side effects, lower relapse rates, and easier treatment protocols, MSCs are quickly becoming a major focus of research into better lupus treatments.
At the same time, the authors continue to study exactly how stem cells work to regulate the immune system. They are also working on ways to improve the safety and effectiveness of both HSCT and MSC treatments. According to Yuan et al, goals for the future include finding better ways to prevent infections, lowering relapse rates, and understanding the long-term effects of stem cell therapy. Researchers are also exploring how to personalize stem cell therapies based on each patient’s unique immune system and genetic background, which could lead to even better outcomes.
Yuan et al. conclude that while traditional lupus treatments have made great strides over the past few decades, there is still a significant need for new and better therapies, especially for patients whose disease does not respond to standard medications.
Stem cell therapy, particularly with mesenchymal stem cells, represents a promising new frontier in the fight against lupus. Ongoing research and clinical trials will help clarify how best to use stem cells to treat SLE safely and effectively, offering new hope for people living with this challenging disease.
Source: Yuan X, Sun L. Stem Cell Therapy in Lupus. Rheumatol Immunol Res. 2022 Jul 6;3(2):61-68. doi: 10.2478/rir-2022-0011. PMID: 36465325; PMCID: PMC9524813.
by admin | Apr 15, 2025 | Mesenchymal Stem Cells, Spinal Cord Injury, Stem Cell Research, Stem Cell Therapy
Spinal cord injury (SCI) is one of the most serious outcomes of spinal trauma. It typically leads to either temporary or permanent loss of sensory, motor, and autonomic nerve functions below the affected area and can significantly impact a person’s quality of life. Worldwide, approximately 10.5 out of every 100,000 people experience SCI. While modern treatments enable 94% of individuals with acute traumatic SCI to survive, long-term survival is often compromised by complications arising after the injury.
In this review, Xia et al. explores the pathophysiological changes that occur following SCI and examines the mechanisms through which MSCs contribute to treatment. The authors also summarize the potential clinical applications of MSCs while addressing the challenges associated with their use and discussing future prospects.
Current Treatment Approaches For SCI
Current therapies for SCI focus on managing the immediate effects of the injury. Standard treatments include stabilizing the spine, surgically decompressing the spinal canal, and initiating rehabilitation programs. These approaches aim to reduce further damage and create conditions that support natural healing processes. However, they do not actively promote the regeneration of damaged nerve cells. The primary goal is to restore neurological function as quickly as possible after addressing the spinal cord compression. Unfortunately, no existing treatment strategies can fully repair damaged nerve cells, leaving an unmet need for innovative therapies.
Primary Spinal Cord Injury
Primary SCI results from direct trauma, such as fractures or dislocations of the vertebrae, which can compress, tear, or even sever the spinal cord. Spinal cord compression is the most common form of primary injury and is often accompanied by damage to blood vessels and the blood-spinal cord barrier (BSCB). The BSCB is a critical structure that maintains the stability and health of the spinal cord by keeping harmful substances out. When the BSCB is compromised, inflammatory molecules and toxic substances infiltrate the injured area, worsening the damage.
Secondary Spinal Cord Injury
Secondary SCI involves a series of biological processes that start within minutes of the initial injury. These changes occur in three overlapping phases: acute (within 48 hours), subacute (48 hours to two weeks), and chronic (lasting up to six months). Secondary injuries can exacerbate the damage caused by the primary injury and often lead to permanent complications.
One of the first effects of secondary SCI is the disruption of the blood supply to the spinal cord, which causes further cell death. As spinal cord cells are destroyed, they release molecules that trigger inflammation. This inflammatory response attracts immune cells to the injury site, which, in turn, release substances that cause additional damage. Neutrophils, a type of immune cell, arrive within an hour of injury and persist for several days, contributing to the worsening of the injury by releasing harmful substances like reactive oxygen species.
The Role of Mesenchymal Stem Cells in SCI
In recent years, mesenchymal stem cells (MSCs) have emerged as a promising option for treating SCI. MSCs are a type of stem cell capable of self-renewal and differentiation into various cell types, making them suitable for tissue repair and regeneration. These cells can be derived from multiple sources, including bone marrow, fat tissue, umbilical cords, and amniotic fluid. MSCs are relatively easy to isolate and store, and their use does not raise significant ethical concerns.
Types of MSCs
The three main types of MSCs used in clinical practice are bone marrow-derived MSCs (BMSCs), adipose-derived MSCs (AD-MSCs), and human umbilical cord-derived MSCs (HUC-MSCs). Each type has unique advantages:
- BMSCs: These cells can differentiate into various tissue types, such as bone, cartilage, and nerve cells. They are effective at reducing inflammation and releasing factors that support nerve regeneration.
- AD-MSCs: Sourced from fat tissue, these cells are easier to obtain in large quantities without causing significant harm. They promote angiogenesis (the formation of new blood vessels) and wound healing by releasing growth factors and other molecules.
- HUC-MSCs: These cells have the highest capacity for proliferation and differentiation. They are smaller in size, allowing them to pass through the BSCB more easily, and they do not pose a risk of fat or vascular embolism.
How MSCs Assist in Treatment of SCI
According to the authors, MSCs offer multiple benefits for SCI treatment, including:
- Immunomodulation: MSCs regulate the immune response at the injury site by interacting with immune cells and releasing anti-inflammatory molecules. This helps reduce inflammation, which is a key factor in secondary injury.
- Neuroprotection and Regeneration: MSCs release neurotrophic factors, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which promote the survival and regeneration of nerve cells. They also inhibit glial scarring, a process that can block nerve regeneration.
- Angiogenesis: MSCs secrete vascular endothelial growth factor (VEGF) and other molecules that encourage the formation of new blood vessels. This improves blood flow to the injured area and helps restore the damaged BSCB.
- Exosome Production: MSCs release exosomes, small vesicles that carry proteins and genetic material to the injury site. These exosomes play a crucial role in reducing inflammation, promoting cell repair, and improving overall tissue recovery.
Future Directions
MSC therapy holds significant promise for improving outcomes in SCI patients. Preclinical studies have demonstrated the ability of MSCs to restore motor function in animal models. In clinical settings, MSCs have shown potential in improving sensory and motor function and aiding bladder control in patients with SCI. However, further research is needed to refine the therapy and address existing challenges.
Mesenchymal Stem Cells: A Promising Path for Spinal Cord Injury Treatment
SCI is a complex condition with devastating consequences for those affected. Current treatments aim to stabilize the injury and create conditions for natural healing but fall short of promoting nerve regeneration. MSCs offer a new avenue for SCI treatment by reducing inflammation, supporting nerve cell regeneration, and improving blood flow to the injured area. While challenges remain, the authors conclude that the advancements in MSC research suggest a bright future for their use in SCI therapy. With continued investigation, MSCs has the potential to become a cornerstone of regenerative medicine for SCI patients.
Source: Xia Y, Zhu J, Yang R, Wang H, Li Y, Fu C. Mesenchymal stem cells in the treatment of spinal cord injury: Mechanisms, current advances and future challenges. Front Immunol. 2023 Feb 24;14:1141601. doi: 10.3389/fimmu.2023.1141601. PMID: 36911700; PMCID: PMC9999104.
by admin | Apr 8, 2025 | Mesenchymal Stem Cells, Parkinson's Disease, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
Parkinson’s disease (PD) is a neurodegenerative disorder affecting millions worldwide, causing debilitating symptoms such as tremors, rigidity, and difficulty walking. Existing treatments primarily manage symptoms without addressing the underlying causes, highlighting the need for more effective therapeutic approaches. Mesenchymal stem cell (MSC) therapy has emerged as a promising option, demonstrating potential neuroprotective, anti-inflammatory, and regenerative benefits.
As part of this review, Tambe et al. examine preclinical and clinical evidence on MSCs and their derivatives, including secretomes and exosomes, in PD management. The authors also analyze challenges and limitations of each approach, including delivery methods, timing of administration, and long-term safety considerations.
The Growing Challenge of Parkinson’s Disease
PD, along with other age-related diseases like Alzheimer’s and stroke, is becoming more prevalent due to increased life expectancy. The disease affects 2–3% of individuals over 65, and by 2040, the number of people living with PD is expected to double. In 2019, PD caused the loss of 5.8 million disability-adjusted life years (DALYs), a significant rise from 2000.
PD symptoms include postural instability, muscle hypertonia, bradykinesia, resting tremor, and cognitive and language abnormalities, all of which negatively impact the quality of life. PD is diagnosed based on motor symptoms, but non-motor symptoms also contribute to disability.
Parkinson’s disease primarily results from the accumulation of α-synuclein and a depletion of dopamine due to neuronal loss in the substantia nigra. It also involves disruptions in multiple pathways, including α-synuclein proteostasis, mitochondrial dysfunction, oxidative stress, and neuroinflammation.
Current Treatments for Parkinson’s Disease
While there is no cure for PD, current symptomatic treatments include levodopa, dopamine agonists, MAO-B inhibitors, COMT inhibitors, deep brain stimulation, and lesion surgery. However, these therapies are limited and do not address the underlying causes of the disease.
Newer interventions like stem cell therapy, neurotrophic factors, and gene therapy aim to address the root causes and potentially slow or stop disease progression.
Cell-based Therapies for Parkinson’s Disease
Cell-based therapies are gaining attention as potential treatments for PD due to their ability to slow disease progression and replace lost dopamine production. Several cell sources are being researched for their therapeutic potential, each with specific advantages and disadvantages.
Mesenchymal stem cells (MSCs) are particularly promising due to their unique properties, including self-renewal and multi-potent differentiation potential. MSCs can differentiate into various cell types, including neuronal-like cells, and exhibit therapeutic effects through both cellular differentiation and the paracrine action of secreted growth factors.
Properties of Mesenchymal Stem Cells (MSCs)
MSCs are plastic-adherent cells capable of self-renewal and differentiation into various lineages, including neurons, adipocytes, osteoblasts, chondrocytes, and endothelial cells. This versatility makes MSCs an attractive option for treating PD.
MSCs also have the potential to exert therapeutic effects through the secretion of factors that promote cell survival, tissue regeneration, and anti-inflammatory actions. In addition to their ability to differentiate into mesodermal lineages, MSCs can produce secretomes and exosomes, which are small vesicles containing proteins, RNA, and other molecules that have demonstrated the ability to influence surrounding cells.
Therapeutic Success of MSCs in PD Management
Preclinical studies on MSCs and their derivatives, including secretomes and exosomes, have shown promising results in PD animal models. MSCs may promote the survival of dopamine-producing neurons and protect against neurodegeneration. Their secretomes, which contain bioactive molecules, can modulate inflammation and stimulate tissue repair. Exosomes, which are extracellular vesicles derived from MSCs, have been shown to improve neuronal function and survival in PD models. These findings suggest that MSC-based therapies could offer a novel approach to managing PD, potentially slowing disease progression and improving motor and cognitive symptoms.
Alternative Delivery Methods for MSC Therapy
One of the significant challenges in MSC therapy for PD is the delivery of these cells to the brain, particularly through the blood-brain barrier (BBB), which restricts the entry of most drugs.
Traditional delivery methods, such as intravenous, intracerebral, and intramuscular routes, have limitations in terms of efficacy and invasiveness.
Recent research has explored intranasal delivery of MSCs and their derivatives as a promising alternative. Intranasal administration could allow MSCs and their secretomes to bypass the BBB, delivering therapeutic agents directly to the central nervous system with minimal invasiveness.
The Future of MSC Therapy for Parkinson’s Disease
MSC-released exosomes and extracellular vesicles are gaining attention as potential treatments for PD due to their improved ability to cross the BBB and target specific cells. These vesicles can transport proteins, growth factors, microRNAs, and other bioactive molecules to recipient cells, potentially enhancing the therapeutic effects of MSCs.
Intranasal delivery of MSCs and their exosomes is an exciting area of research, offering a less invasive method for delivering therapy directly to the brain. This approach could lead to improved outcomes in PD management, especially if combined with other therapies that address the underlying causes of the disease.
Tambe et al. conclude that MSC therapy and its derivatives, such as secretomes and exosomes, hold significant promise for the treatment of Parkinson’s disease. However, challenges such as MSC heterogeneity, delivery methods, and long-term safety must be addressed before MSC-based therapies can become a mainstream treatment for PD.
Source: Tambe P, Undale V, Sanap A, Bhonde R, Mante N. The prospective role of mesenchymal stem cells in Parkinson’s disease. Parkinsonism Relat Disord. 2024 Oct;127:107087. doi: 10.1016/j.parkreldis.2024.107087. Epub 2024 Aug 10. PMID: 39142905.
by admin | Mar 27, 2025 | Mesenchymal Stem Cells, Spinal Cord Injury, Stem Cell Research, Stem Cell Therapy
Spinal cord injury (SCI) is a devastating condition that causes severe nerve damage, leading to impaired movement, sensation, and bodily functions. The injury sets off a series of damaging processes, including excessive inflammation, loss of essential nutrients, and scar tissue formation.
These factors prevent the regeneration of nerve cells, making recovery difficult. Traditional treatments provide limited improvement, but recent research by Lui et al. suggests that mesenchymal stem cells (MSCs) offer hope for patients with SCI.
How SCI Disrupts the Microenvironment
Following SCI, the body experiences a host of negative effects. Initially, the injury causes direct damage to nerve cells, leading to inflammation and the release of harmful substances.
The body’s attempt to repair the damage often backfires, as excessive inflammation worsens tissue destruction and inhibits nerve regeneration. Additionally, the blood-spinal cord barrier (BSCB) becomes compromised, allowing immune cells to flood the injured site.
These immune cells produce harmful molecules like reactive oxygen species (ROS) and cytokines, further aggravating the damage.
The prolonged inflammation creates a hostile environment that prevents new nerve growth and leads to the formation of scar tissue that blocks potential regeneration.
The Role of MSCs in Repairing the Spinal Cord
The ability of MSCs to repair spinal cord injuries (SCI) lies in their powerful secretions of bioactive molecules, which help regulate inflammation, promote nerve cell survival, and enhance tissue repair.
MSCs suppress harmful immune responses by decreasing the activity of pro-inflammatory cells like T-cells and macrophages while promoting anti-inflammatory pathways to minimize further nerve damage. They also release neurotrophic factors that nourish and support nerve cells, encouraging the survival and growth of new neurons to improve recovery.
Additionally, MSCs help prevent the formation of dense glial scar tissue, which can obstruct axon regrowth, by regulating proteins like MMP-2 and BDNF that break down scar tissue and create space for new nerve connections. Furthermore, MSCs contribute to angiogenesis, promoting blood vessel growth to ensure that the injured site receives adequate nutrients and oxygen for healing.
Optimizing MSC Therapy for SCI
To ensure MSC therapy is effective for SCI treatment, the authors call for additional research to determine the most efficient timing, dosage, and delivery method.
Timing for MSC Transplantation
Studies suggest that MSCs work best when introduced during the subacute phase (approximately two weeks after injury). This timing allows MSCs to reduce inflammation while the injury is still healing. If administered too early, the highly inflammatory environment may kill MSCs before they can have a therapeutic effect. If given too late, scar tissue may already be well established, limiting their benefits.
Optimal Dosage
According to Liu et. al, research on animals suggests that higher doses of MSCs (greater than one million cells) lead to better functional recovery.
However, an excessively high dose might provoke an unwanted immune response. In humans, doses typically range from 10 to 100 million cells, though further research is needed to determine the optimal amount.
Optimizing MSC Delivery for Spinal Cord Repair
MSCs can be delivered in different ways. Intravenous (IV) injection is the least invasive, but many cells get trapped in organs like the lungs before reaching the spinal cord. Direct injection into the injury site is more targeted but carries risks of additional damage. Intrathecal injection (into the spinal fluid) is a promising middle ground, as it allows MSCs to circulate in the cerebrospinal fluid and reach the injury without additional trauma.
Advancing MSC Therapy for Spinal Cord Injury: Challenges and Future Prospects
Although MSC therapy holds great promise, several challenges remain before it can become a routine treatment for SCI. Researchers need to refine techniques for improving MSC survival, homing (their ability to find the injured site), and integration into the spinal cord. Scientists are also exploring genetic modifications and biomaterial scaffolds to enhance MSC effectiveness. Additionally, large-scale clinical trials are necessary to confirm safety and efficacy in human patients.
In the future, personalized MSC therapy – where treatment is tailored to each patient’s specific injury and biological factors – could revolutionize SCI treatment.
Liu et al. conclude that ongoing advancements in stem cell research, MSC transplantation has the potential to improve the quality of life for SCI patients by restoring lost function and promoting recovery in ways that were once thought impossible.
Source: Liu, Y., Zhao, C., Zhang, R. et al. Progression of mesenchymal stem cell regulation on imbalanced microenvironment after spinal cord injury. Stem Cell Res Ther 15, 343 (2024). https://doi.org/10.1186/s13287-024-03914-x
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