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 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 8, 2024 | Osteoarthritis, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Osteoarthritis (OA) is the most common form of arthritis and occurs as a result of the protective cartilage, found on the ends of the bones, degenerates over time. While OA can occur in any joint, it is most commonly found to occur in the hands, hips, spine, and knee.
An estimated 365 million people worldwide are currently living with some form of knee OA. Although there have been improvements in conventional treatment methods that have shown some benefit, there is no therapy or drug that can prevent or treat the development of OA in the knee.
Recent phase I/II trials using mesenchymal stromal cells (MSCs) derived from bone marrow (BM) and adipose tissue have demonstrated the feasibility, safety, and clinical and structural improvements in focal or diffuse disease.
Considering the findings of these phase I/II trials, Orrego et al. conducted this study to better assess the safety and efficacy of the intra-articular injection of single or repeated umbilical cord-derived (UC) MSCs in knee OA.
The target population of this study was individuals between the ages of 40-65 with symptomatic knee pain for at least 3 months with grade 1-3 Kellgren-Lawrence radiographic changes in the targeted knee, without meniscus rupture.
The authors divided participants of this study into three specific groups, a control group which received intra-articular knee injections of hyaluronic acid (HA) at baseline and 6 months; the MCS-2 group, which received UC-MSCs at baseline and 6 months; and the MSC-1 group, who received UC-MSCs at baseline followed by placebo injection at 6 months.
At the conclusion of this study’s 12 months follow-up period, Orrego et al. found that the group with repeated UC-MSC intra-articular injections, or MCS-2, experienced significant clinical changes in total WOMAC, pain component, and VAS when compared with the control group. The authors also found that only patients in the MSC groups experienced significant amelioration of pain and disability at 6 and 12 months. The authors also reported no safety signals were detected in the experimental groups as compared with the HA controls.
Considering these findings, the authors conclude that the use of MSCs produces anti-inflammatory properties in response to tissue damage or inflammation that demonstrates suppressive effects on the maturation of dendritic cells, macrophages, Natural Killer, and cytotoxic T-lymphocytes.
While these results appear promising, the authors point out that even if all MSC trials report a good safety record and improvements in cartilage quality, the use of autologous cell therapy does come with some limitations. Among these limitations include a dramatic decline of bone precursor cells when these cells are derived from bone marrow. Studies have also shown reduced chondrogenic activity of MSCs in cultures obtained from individuals with advanced forms of OA. For these reasons, and considering the findings in this study, the authors highlight that allogeneic sources of MSCs have been shown to express superior clonogenicity, migration, and paracrine capacities.
The authors conclude that the repeated UC-MSC dose strategy utilized in this study led to a favorable safety profile and improved clinical results for the treatment of long-term pain in knee OA patients.
Source: Jose Matas, Mario Orrego, Diego Amenabar, Catalina Infante, Rafael Tapia-Limonchi, Maria Ignacia Cadiz, Francisca Alcayaga-Miranda, Paz L. González, Emilio Muse, Maroun Khoury, Fernando E. Figueroa, Francisco Espinoza, Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial, Stem Cells Translational Medicine, Volume 8, Issue 3, March 2019, Pages 215–224, https://doi.org/10.1002/sctm.18-0053
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
by admin | Jan 31, 2024 | Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Acute and chronic pancreatitis are associated with local and systemic inflammation that is linked to a host of serious health issues. A result of the digestive juices and enzymes attacking the pancreas, pancreatitis currently has no definite treatment.
Currently, it is estimated that over 6 million people worldwide are afflicted by acute or chronic pancreatitis with the number of diagnoses appearing to be steadily increasing.
The rising interest in stem cell therapy being used to potentially treat a wide variety of other diseases has led to interest in exploring it as a way to aid in the treatment of both acute and chronic pancreatitis.
As part of this review, Chela et al. examine numerous studies using commonly used stem cells to explore their promise in the treatment of pancreatitis.
A number of studies are utilizing stem cells to repair and replace tissue damaged as a result of numerous gastrointestinal diseases, including acute and chronic pancreatitis. In the case of using stem cells, and specifically mesenchymal stem cells (MSCs), to treat pancreatitis, researchers are interested in the ability of these stem cells to regenerate damaged cells and to influence the immunological and inflammatory response resulting from this condition.
A significant issue that has stymied progress in the ability of the pancreas to self-repair and regenerate when affected by pancreatitis is the perceived lack of stem cells found specifically in the tissue of the pancreas. While there has been conflicting research into whether or not stem cells exist in pancreatic tissue, the research reviewed by the authors indicates that there appears to be a tiny amount of stem cells located within pancreatic tissue.
Considering this and considering that additional research indicates that other stem cells found in the pancreas appear to originate from bone marrow (BM), the authors believe the ability of MSCs’ ability to differentiate will support the healing of the pancreas; these include stem cell sources from BM, adipose tissue, umbilical cord, and induced pluripotent stem cells (iPSCs).
Source: “Stem cell therapy: a potential for the perils of pancreatitis – PMC – NCBI.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433995/.
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