by admin | Feb 22, 2024 | Spinal Cord Injury, Adipose, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
With more than 17,000 people in the US sustaining a spinal cord injury (SCI) each year and an estimated combined cost to healthcare and the workforce exceeding $40 billion, the condition has significant personal and socioeconomic implications. In addition, SCIs have limited pharmacological treatment options to support the regeneration of nerve damage.
Considering the limited treatment options for this condition, the field of regenerative medicine, and specifically the use of stem cells, has recently drawn interest as a potential therapeutic treatment option for paralysis resulting from SCIs.
In this report, Bydon et al. summarize findings of the ongoing multidisciplinary phase 1 clinical trial exploring the safety and efficacy of intrathecal autologous adipose tissue-derived (AD) mesenchymal stem cells (MSCs) in patients with blunt, traumatic SCI.
Specifically, as part of this report, the authors describe the outcome of the first patient with C3-4 SCI treated with AD-MSCs. At the time of SCI, neurologic examination revealed complete loss of motor and sensory function below the level of injury; an injury diagnosed as an American Spinal Injury Association (ASIA) grade A SCI.
After undergoing initial treatment, including C2-6 posterior cervical decompression and fusion, improvement in motor and sensory function was demonstrable. However, neurological gains plateaued 6 months after sustaining injury.
Upon enrollment into the CELLTOP clinical trial 9 months after injury, the patient’s neurologic status was found to be ASIA grade C and imaging revealed bilateral myelomalacia at the C3 level and at the C2-6 decompression and fusion. Additionally, an open biopsy of adipose tissue found in the abdominal wall was performed 8 weeks prior to receiving an initial intrathecal injection.
After receiving an intrathecal injection of 100 million autologous AD-MSCs 11 months after injury, the patient was observed for clinical signs of efficacy at 3, 6, 12, and 18 months following injection.
Bydon et al. observed progressive improvement in upper extremity motor scores and considerable improvement in lower extremity scores at 18 months following injection. The patient also demonstrated consistent improvement in ASIA sensory score, including improvements in pinprick and light touch scores at follow-up after 18 months. The authors reported patient improvements in Capabilities of Upper Extremity score, quality of life (as measured by Global Health Score), and in physical and occupational therapy measures. Other than a moderate headache on day 2, no other safety issues or adverse events were reported.
While further clinical trial is required, the authors conclude that intrathecal AD-MSC administration may be a relatively noninvasive and safe therapeutic option for patients with SCI to improve their neurologic status after reaching a ceiling effect in terms of spontaneous recovery.
Source: “First Report From a Phase 1 Trial of Autologous Adipose Tissue ….” 27 Nov. 2019, https://www.mayoclinicproceedings.org/article/S0025-6196(19)30871-7/fulltext.
by admin | Feb 22, 2024 | ALS, Stem Cell Research, Stem Cell Therapy
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of upper and lower motor neurons resulting in paralysis, respiratory insufficiency, difficulties speaking and swallowing, stiffness and spasticity, and muscle atrophy. Commonly known as Lou Gehrig’s disease, after the baseball player was diagnosed with it, ALS is diagnosed in an estimated 5,000 Americans each year.
Currently, ALS has a median survival time of 4.32 years and no known cure. As part of the effort to develop new therapeutic options to slow the progression of ALS, stem cell (SC) transplantation has shown potential in recent clinical trials.
In this review, Aljabri et al. examine the results of various clinical trials exploring the use of stem cell therapy as a viable therapy for ALS. Specifically, the authors identified six studies determined to have met the established criteria for review.
As part of this research, the authors examined the efficacy of SC transplantation in patients with ALS. Studies examined included a number of routes of administration, including subcutaneous, combined intrathecal and intramuscular, intravenous and intralumbar injections, and intrathecal approach. These studies all demonstrated slower decline or significant improvement as measured on the ALS Functional Rating Scale (ALSFRS-R).
While there appears to be a benefit in this application, the authors of two of the studies did not observe a significant difference in the efficacy between treatment and placebo groups after injections.
Additionally, the authors noted that all three studies using bone marrow mesenchymal stem cells (BM-MSC) demonstrated a significant decrease in the progression of disease burden and an overall slower decline in the ALSFRS-R score. On the other hand, studies that used granulocyte colony-stimulating factor (G-CSF) did not demonstrate a significant benefit.
While these results are promising, the authors point out limitations of the study that make it difficult to identify the long-term effects and long-term benefits associated with SC therapy. These limitations include short follow-up periods of either 6 or 12 months and the loss of patients during follow-up, both of which compromise the ability to determine long-term benefits and effects with fidelity.
Aljabri et al. also highlights many challenges associated with the introduction of SCs into the CNS. Among these challenges include the increased risk of AEs associated with the multiple SC injections required to deliver therapeutic doses and determining the most appropriate route of injection for therapeutic benefits.
The authors conclude that early clinical trials have made great progress in delineating the safety of SC therapy in the treatment of ALS. What remains to be determined is how effective SCs are compared to other forms of therapy. While the current data of SC therapy hold great promise, more properly designed clinical trials are needed to verify their benefit.
Source: Aljabri A, Halawani A, Bin Lajdam G, Labban S, Alshehri S and Felemban R (2021) The Safety and Efficacy of Stem Cell Therapy as an Emerging Therapy for ALS: A Systematic Review of Controlled Clinical Trials. Front. Neurol. 12:783122. doi: 10.3389/fneur.2021.783122
by admin | Feb 15, 2024 | Osteoarthritis, Exosomes, Extracellular Vesicles, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Osteoarthritis (OA) is the most common form of arthritis and is estimated to affect nearly 365 million people worldwide. Characterized as an inflammatory disease, OA slowly progresses over time and results in the gradual loss of the protective cartilage found on the ends of the bones.
While the specific cause of OA has yet to be determined, a growing body of evidence suggests the chondrocyte inflammatory response resulting from elevated levels of pro-inflammatory cytokines is a critical factor in the development and progression of OA.
Recent evidence also suggests that mesenchymal stem cell-derived exomes (MSCs-Exos) exhibit beneficial anti-inflammatory responses in several inflammatory diseases, including OA.
In this study, Wang et al. explore the role of human umbilical cord-derived MSCs-Exos (hUC-MSCs-Exos) in treating the inflammation of chondrocytes and its related mechanisms.
As part of this study, the authors report that supplementing the observed chondrocyte inflammation models with hUC-MSCs-Exos demonstrated the ability to reduce the inflammation of chondrocytes caused by the inflammatory factor IL-1β.
Additionally, activation and polarization of synovial macrophages to M1 phenotypes also contribute to the progression of OS. As part of this study, Wang et al. report that hUC-MSC-Exos demonstrated a protective effect against M1 macrophage-induced chondrocyte damage and cell death.
Wang et al. indicate that the results of this study confirm the anti-inflammatory effects of hUC-MSCs-Exos in the human articular chondrocytes inflammation model. The authors also conclude that hUC-MSCs-Exos may be used as a potential cell-free treatment for chondrocyte inflammation in OA.
Source: Wang S, Jiang W, Lv S, et al. Human umbilical cord mesenchymal stem cells-derived exosomes exert anti-inflammatory effects on osteoarthritis chondrocytes. Aging (Albany NY). 2023;15(18):9544-9560. doi:10.18632/aging.205034
by admin | Feb 8, 2024 | Spinal Cord Injury, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Spinal cord injury is one of the most complicated and serious pathological impairments affecting the central nervous system. Since the human body is unable to regenerate and repair the spinal cord after injury, there is a high likelihood of suffering permanent damage and disability.
Often compounding the issue of SCI, secondary events occurring after the initial injury to the spinal cord significantly reduce cell migration and axonal regrowth and limit repair and regeneration.
Recently, transplantation of mesenchymal stem cells (MSCs) has been shown to promote the repair of injured spinal cord tissues in animal models. However, as Qu and Zhang highlight in this review, there remain many unanswered questions that are essential for improving the effects of this MSC therapy. As such, the authors focus this review on recent information about the behavior and function of MSCs in SCI, the function of biomaterials to direct the behavior of MSCs, and the attempt to emphasize combinational strategies such as tissue engineering for functional improvements of SCI.
There are studies showing that the migratory and homing capacities of MSCs are closely related to their engraftment and regeneration ability. Considering this, the authors highlight the importance of having MSCs migrate and integrate into host spinal cord tissue. Since MSC homing toward injured tissue is not an efficient process, and to ensure a more effective stem cell therapy outcome, it is important that these transplanted cells be introduced in a way that increases the migratory potential of healthy MSCs to the site of injured tissue.
Additionally, while transplanted cells have been identified adjacent to neurons after SCI, the surviving number of grafted and differentiated neurons was too small to be considered to contribute to functional recovery after SCI. However, data suggests that the ability of MSCs to secrete soluble factors or vesicles rather than engrafting and transdifferentiating might serve an important role in SCI repair.
The authors also point to studies that indicate MSC implantation could promote a therapeutic effect and functional recovery in experimental SCI animal models. The authors believe that this is a result of MSCs ability to differentiate into specialized neuronal and glial cell lineages after transplantation. While MSC transplantation has not yet been proven to be an effective and reliable therapy for SCI, additional studies need to be done before the therapy is utilized in clinical applications.
MSCs respond to the local environment in multiple ways and represent the most promising exosomes for neuropathic applications. Qu and Zhang conclude this review by calling for more intensive studies examining the potential benefits of combining MSCs with nerve tissue-engineered scaffolds to direct cell behaviors after SCI, including growth, migration, and differentiation.
Source: “Roles of Mesenchymal Stem Cells in Spinal Cord Injury – Hindawi.” https://www.hindawi.com/journals/sci/2017/5251313/.
by admin | Feb 1, 2024 | Psoriasis, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Characterized by scaly white or erythematous plaques, psoriasis is a chronic autoimmune dermatological disease most often appearing on the scalp, genitalia, lumbosacral area, and extensor surfaces of the limbs.
Affecting an estimated 125 million people worldwide, the condition most commonly is observed in those between the ages of 15 and 25 years of age.
The most recent advancements in the development of biological treatment have revolutionized the treatment of the condition for those with moderate to severe psoriasis, achieving clear or nearly clear skin with long-term success.
However, these treatments in their current form have not been proven to cure psoriasis completely. Additionally, a growing number of those suffering from severe psoriasis are not responding to these current therapeutic treatment options.
Recently, stem cell therapy, including regulatory T-cells, hematopoietic stem cell transplantation, and mesenchymal stromal cells (MSCs) have been used in patients with recalcitrant psoriasis. In this review, Naik discusses stem cell treatment options available for psoriasis.
Regulatory T-cells, or Tregs, regulate or suppress other immunocytes by modulating their responses to the endogenous environment and antigens, which helps to avoid autoimmune reactions and chronic inflammation. Several treatments for psoriasis, including many biologics currently being used, appear to increase the number of Tregs and their performance in patients with psoriasis. This finding led Naik to conclude that, despite their high cost, Treg-based therapies may have the ability to interfere with the pathogenesis of psoriasis.
MSCs have been found to have a significant role in adaptive immunity. This immune-enhancing activity typically occurs in partnership with a number of immune cells, including neutrophils, dendritic cells, monocytes, natural killer cells, macrophages, B-cells, and T-cells. While several Phase I and II studies have not demonstrated significant toxicity, the author calls for more extensive controlled trials to better understand the efficacy and long-term safety of MSCs in this application.
The favorable results observed when using hematopoietic stem cells (HSCT) in a wide range of autoimmune conditions, including lymphoma, leukemia, lupus, diabetes, rheumatoid arthritis, and multiple sclerosis, led to interest in using these cells in patients with psoriasis. Interestingly, improvements in psoriasis have been observed in patients who have undergone allogeneic (rather than autologous) HSCT, suggesting that hematopoietic stem cells could contribute as a primary cause of psoriasis.
Naik concludes that the application of stem cells in the treatment of psoriasis raises hope for the development of a safe and effective therapy for those suffering from severe forms of the condition. While more data is required before clinical application, MSCs could be a promising therapy for the treatment of psoriasis.
Source: Naik PP. Stem cell therapy as a potential treatment option for psoriasis. An Bras Dermatol. 2022;97(4):471-477. doi:10.1016/j.abd.2021.10.002
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