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
by admin | Mar 18, 2025 | Mesenchymal Stem Cells, Spinal Cord Injury, Stem Cell Research, Stem Cell Therapy
Spinal cord injury (SCI) can lead to lasting health challenges, impacting motor, sensory, and autonomic functions. Recovery from such injuries is particularly difficult due to the central nervous system’s limited ability to repair itself. As a result, scientists have turned to stem cell therapies, particularly mesenchymal stem cells (MSCs), as a potential solution to help treat traumatic spinal cord injuries (TSCI).
In this review, Montoto-Meijide et al. explore the role of stem cell therapy in TSCI treatment, the safety and efficacy of MSCs, and the ongoing research aimed at improving these therapies.
Spinal Cord Injury and the Need for Effective Treatments
A spinal cord injury results from trauma that damages the spinal cord, leading to various degrees of paralysis and loss of sensory functions. Recovery is limited because the central nervous system does not regenerate easily, meaning that cells, myelin (which insulates nerve fibers), and neural connections are difficult to restore. Traditional treatments focus on alleviating symptoms and preventing further injury, but they do not offer a cure or promote regeneration. As a result, researchers are exploring stem cell therapies, which have shown potential in regenerating damaged tissues and promoting recovery.
An Overview of Mesenchymal Stem Cells (MSCs)
Stem cells are unique in that they can self-renew and differentiate into different types of cells. MSCs are a type of adult stem cell that can develop into various cell types, including bone, cartilage, muscle, and fat cells. MSCs are particularly promising in SCI treatment because of their ability to regenerate tissues and support healing. These cells have shown anti-inflammatory, anti-apoptotic (preventing cell death), and angiogenic (promoting new blood vessel growth) properties, all of which could aid in the healing of spinal cord injuries.
There are different types of stem cells, including embryonic and adult stem cells. Each source has its advantages and drawbacks. Bone marrow MSCs are the most commonly used in research and clinical trials, but adipose tissue and umbilical cord MSCs are gaining attention due to their availability and regenerative capabilities.
The Role of MSCs in Treating Spinal Cord Injuries
MSCs offer several benefits when applied to SCI treatment. They can promote tissue repair, reduce inflammation, and enhance the formation of new blood vessels. When introduced into an injured spinal cord, MSCs have been shown to:
- Promote axonal (nerve fiber) regeneration
- Reduce inflammation around the injury site
- Support the survival of nerve cells
- Enhance the formation of new blood vessels, aiding in tissue repair
These capabilities make MSCs an exciting avenue for research into TSCI treatment. Clinical trials and studies have shown that MSCs can lead to improvements in motor and sensory functions, although the extent of these improvements varies.
Clinical Evidence and Findings
A systematic review of clinical studies involving MSCs for TSCI was conducted, analyzing data from 22 studies, including 21 clinical trials. According to the authors, these findings suggest that MSC-based therapies can lead to improvements in sensory and motor functions, although these effects are often more pronounced in sensory functions than motor functions. Improvements in patients’ ASIA (American Spinal Injury Association) impairment scale grades have been reported, indicating positive outcomes for many individuals.
The safety of MSC therapies was also a key focus of these studies. Overall, MSC-based treatments were found to have a good safety profile, with no significant adverse effects such as death or tumor formation reported in clinical trials. Some studies did report mild side effects, such as temporary inflammation or mild discomfort, but these were generally short-lived and not severe.
The Future of MSC Therapy and Other Potential Treatments
MSC therapy represents one of the most promising areas of research for TSCI, but it is not the only potential treatment. Other therapies, including gene therapies, neurostimulation techniques, and tissue engineering approaches, are also being explored to address the challenges of spinal cord injury. The authors believe these approaches could complement MSC therapies or offer new avenues for healing and recovery.
For MSC therapy to become a standard treatment for TSCI, additional research is needed. Clinical trials with larger patient groups, longer follow-up periods, and standardized protocols will be necessary to better understand how MSCs can be used most effectively in treating spinal cord injuries. Additionally, researchers are exploring the best stem cell sources, optimal timing for treatment, and the ideal dosage to maximize benefits.
A Promising Future for Spinal Cord Injury Treatment
While spinal cord injuries are currently devastating and challenging to treat, stem cell therapy, particularly with MSCs, offers a hopeful future. Early studies suggest that MSCs can help promote tissue repair, reduce inflammation, and improve motor and sensory functions, although further research is needed to confirm these findings and explore long-term effects. The scientific community continues to make strides in understanding how MSCs and other therapies can help people with TSCI recover and regain functionality, offering hope for the future.
Source: Montoto-Meijide R, Meijide-Faílde R, Díaz-Prado SM, Montoto-Marqués A. Mesenchymal Stem Cell Therapy in Traumatic Spinal Cord Injury: A Systematic Review. Int J Mol Sci. 2023 Jul 20;24(14):11719. doi: 10.3390/ijms241411719. PMID: 37511478; PMCID: PMC10380897.
by admin | Jan 24, 2025 | Autoimmune, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
The onset of autoimmune diseases is related to unbalanced immune homeostasis and leads to the injury and failure of several organ specific tissues. Currently estimated to affect 8-10% of the population, these autoimmune diseases are associated with serious impairment, high mortality rate, and significant medical costs.
The discovery of stem cells, and specifically mesenchymal stem cells (MSCs), has created new opportunities for accelerating tissue regeneration. MSCs possess the ability to self-renew and differentiate into a wide range of cell types that fill a critical role in immunomodulation and regenerative therapy.
In this review, Jasim et al. share the latest research on the efficiency and feasibility of MSCs in the clinical treatment of several autoimmune disorders including rheumatoid arthritis, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, liver disease, and Sjogren’s syndrome.
To date, most of these autoimmune disorders have been treated with a number of conventional drugs, including non-steroidal anti-inflammatory drugs. However, with many of these conditions, these drugs have been observed to contribute to liver injury, gastrointestinal injury, kidney side effects, BM suppression, and psychological disorders, making the development of new and safe therapeutic approaches an important issue. This has led to significant interest in exploring the potential benefits of MSC therapy in treating autoimmune diseases.
MSCs are easily collected from a variety of sources, including umbilical cord (UC), Wharton’s jelly (WJ), adipose tissue, bone marrow (BM), teeth and menstrual fluid. Research has demonstrated that MSCs regulate their local environment, cellular communications, and the release of several factors. MSCs are also able to migrate and differentiate into damaged tissue and can release growth factors, cytokines, and chemokines, which assists in improving tissue regeneration.
The research evaluated by the authors as part of this review, coupled with MSC’s high proliferation ability, multipotent differentiation capacity, anti-inflammatory and immunomodulatory properties, and regenerative potential, led to the conclusion that there was no remarkable association between mesenchymal stem cell therapy (MSCT) and tumor and infection with the treatment determined to be safe and feasible.
Jasim et al. also concluded that there is still a lack of understanding of the specific mechanisms through which the MSCT ameliorates these various autoimmune diseases that must be addressed as a way to enhance the future clinical use of MSCs.
Source: Jasim SA, Yumashev AV, Abdelbasset WK, et al. Shining the light on clinical application of mesenchymal stem cell therapy in autoimmune diseases. Stem Cell Res Ther. 2022;13(1):101. Published 2022 Mar 7. doi:10.1186/s13287-022-02782-7
by admin | Jan 17, 2025 | Chondrocyte, Mesenchymal Stem Cells, Osteoarthritis, Stem Cell Research, Stem Cell Therapy
Osteoarthritis (OA) continues to be the most common form of degenerative joint disease in the United States and around the world.
According to the World Health Organization (WHO), 528 million people worldwide were living with osteoarthritis (OA) in 2019, which is an increase of 113% since 1990. The Global Burden of Disease Study 2021 found that 595 million people had OA in 2020, which is 7.6% of the global population. The Centers for Disease Control and Prevention (CDC) estimates that over 32.5 million adults in the U.S. currently live with OA.
Despite the tremendous increase in the global incidence of OA, there are no effective pharmaceutical therapies that are able to restore the original structure and function of damaged articular cartilage.
Considering this, cell-based therapies for OA and other orthopedic disorders have become a primary area of current research and development.
In this review, Mobasheri et al. focus on the structure and function of articular cartilage, the pathogenesis of OA, and explore the challenges associated with cartilage repair and regeneration using cell-based therapies that utilize chondrocytes and mesenchymal stem cells (MSCs).
Articular cartilage (AC) has demonstrated a very poor ability to repair and regenerate. Being largely avascular and containing no blood vessels, AC lacks the blood flow required in the biological repair response process.
Overtime, and with age, cartilage loses its already limited capacity for repair and damaged cartilage is typically replaced by fibrocartilage-like scar tissue. With no successful surgical technique demonstrating success in stimulating AC repair and regeneration, autologous chondrocyte implantation (ACI) has emerged as one of the most widely used cell-based repair strategies for articular cartilage. Performed on over 12,000 patients worldwide, ACI has encouraged the growth of durable cartilage-like tissue and demonstrated the ability to significantly reduce pain in patients.
Recent studies have also demonstrated that the immunomodulatory properties of MSCs are able to be exploited for the treatment of many inflammatory and rheumatic conditions, including OA. Specifically, the ability of MSCs to migrate to the site of an injury, induce peripheral tolerance, and inhibit the release of pro-inflammatory cytokines has been observed to promote tissue repair and the survival of damaged cells.
Considering these advances, Mobasheri et al. report that tissue engineering with chondrocytes and MSCs is now considered to be a promising way of repairing articular cartilage lesions. While there is significant evidence of the potential of these cell-based therapeutic treatment options, the authors also point out fundamental weaknesses associated with the models available to date.
Included among these weaknesses is the fact that none of the engineered tissue currently available possess the normal zonal organization of chondrocytes observed in vitro and considered to be the prerequisite for normal cartilage function and for the success of any future clinical application.
While there are still weaknesses associated with tissue utilizing engineering and cell-based therapies to repair cartilage in OA and other orthopedic conditions that require further research, the authors conclude that these emerging therapeutic options hold tremendous promise for managing OA in the future.
Source: Ali Mobasheri, Gauthaman Kalamegam, Giuseppe Musumeci, Mark E. Batt,
Chondrocyte and mesenchymal stem cell-based therapies for cartilage repair in osteoarthritis and related orthopaedic conditions, Maturitas,Volume 78, Issue 3, 2014, Pages 188-198, ISSN 0378-5122.
by admin | Jan 10, 2025 | Mesenchymal Stem Cells, Orthopedic Injuries, Osteoarthritis, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
Osteoarthritis (OA) is a prevalent and disabling joint condition that imposes significant health and economic burdens globally. Between 2006 and 2016, the global percentage change in years lived with disability due to OA increased by 31.5%. Knee osteoarthritis (KOA) is the most common form, primarily affecting older adults and those who are obese. Symptoms of KOA include pain, swelling, stiffness, and decreased mobility. KOA’s development involves more than just mechanical wear and tear. It is influenced by genetic and environmental factors, leading to the breakdown of articular cartilage, inflammation, and changes in the underlying bone.
Pathogenesis of KOA
The deterioration in KOA is complex. It begins with mechanical stress and progresses through a cascade of biological processes. Key players in cartilage maintenance are chondrocytes and the extracellular matrix (ECM). Chondrocytes, although only 2% of cartilage volume, are crucial and respond to inflammatory signals that disrupt the balance between ECM production and degradation, limiting cartilage regeneration.
Traditional treatments for KOA are primarily focused on pain management and symptomatic relief, with limited success in regenerating damaged cartilage.
Emerging Cell-Based Therapies For KOA
Mesenchymal Stromal Cells (MSCs) and Exosomes
Recent advances in cell-based therapy for KOA involve mesenchymal stromal cells (MSCs) and their secreted exosomes. MSCs are multipotent cells found in various tissues, including bone marrow, adipose tissue, and synovial fluid. They have the ability to differentiate into multiple cell types, including chondrocytes, and secrete exosomes that carry bioactive molecules.
MSC Selection and Preparation
MSCs can be derived from different sources, including bone marrow, adipose tissue, and umbilical cord tissue. Each source has unique properties and benefits. For instance, bone marrow-derived MSCs (BM-MSCs) are commonly used due to their extensive research background, while adipose tissue-derived MSCs (AT-MSCs) also show promising results.
Exosomes, extracellular vesicles released by MSCs, play a vital role in cell communication. They transfer lipids, nucleic acids, and proteins that can modulate cell behavior and promote cartilage repair.
Mechanisms of MSC-Based Therapy
Effects on Chondrocytes
MSC therapy promotes chondrocyte health by increasing chondrogenesis, improving cell proliferation, reducing apoptosis, and maintaining autophagy. MSCs stimulate chondrocyte activity through growth factors, enhancing their ability to regenerate cartilage. Studies show that MSCs and their exosomes can improve chondrocyte proliferation and reduce apoptosis, helping maintain cartilage integrity.
Impact on the ECM
Regulating the ECM’s balance between synthesis and breakdown is crucial for treating KOA. MSCs influence this balance by modulating matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of MMPs (TIMPs). For example, BM-MSCs can adjust the ratio of MMP-13 to TIMP-1, improving cartilage matrix composition.
Influence on Inflammation
Inflammation is a significant factor in KOA. MSCs and their exosomes can reduce pro-inflammatory cytokines (e.g., IL-1β, TNF-α) and enhance anti-inflammatory responses. This reduction in inflammation helps alleviate cartilage damage and improve joint function.
Immunomodulation
MSCs can modulate immune responses by influencing macrophage polarization. They can shift macrophages from a pro-inflammatory (M1) to an anti-inflammatory (M2) state, which helps reduce inflammation and promote tissue repair.
Mitochondrial Function
MSCs can also enhance mitochondrial function in chondrocytes. Mitochondrial transfer from MSCs to chondrocytes improves their energy production and reduces oxidative stress, which is crucial for maintaining cell function and delaying the progression of OA.
Paracrine Effects
The paracrine effects of MSCs, particularly through exosomes, involve the transfer of molecular signals to nearby cells. This signaling can promote cartilage repair and modulate inflammation and cell survival.
Overcoming Obstacles and Refining MSC Therapies for Better Outcomes
While MSC-based therapies show promise, there is a lack of standardized protocols for cell selection and preparation. Additionally, the exact mechanisms through which MSCs and exosomes exert their effects are still being studied. Xiang et al. call for further research to establish standardized methods and fully understand how these therapies work.
External physical conditions, such as hypoxia and magnetic fields, can affect MSC behavior and cartilage regeneration. Hypoxic conditions have been shown to enhance chondrogenesis, while magnetic fields can boost MSC differentiation and cartilage repair. Understanding these effects can improve treatment strategies.
Promising Advances in Cell-Based Therapies for Osteoarthritis Management
Osteoarthritis, particularly knee osteoarthritis, represents a major challenge due to its complex pathogenesis and significant impact on quality of life. Traditional treatments offer limited solutions for cartilage regeneration. However, advances in cell-based therapies, including MSCs and their exosomes, provide promising alternatives. These therapies work through various mechanisms, including enhancing chondrocyte function, modulating inflammation, and improving ECM balance. The authors conclude that ongoing research and standardization efforts will be crucial in optimizing these treatments and addressing the unmet needs in osteoarthritis management.
Source: Xiang, XN., Zhu, SY., He, HC. et al. Mesenchymal stromal cell-based therapy for cartilage regeneration in knee osteoarthritis. Stem Cell Res Ther 13, 14 (2022). https://doi.org/10.1186/s13287-021-02689-9
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