Mesenchymal stromal cells (MSCs) have repeatedly demonstrated the capacity to limit injury and promote regeneration through signaling and secretion of trophic factors. Considering this, MSCs have been increasingly used as a treatment for a wide variety of injuries and immune-related, infectious, and degenerative diseases.
In this review, Jahromi et al. provide a brief overview of the fate and efficacy of intramuscular (IM) delivered MSCs and identify the gaps that require additional study before IM-delivered MSCs are adopted as a primary treatment of systemic diseases.
Specifically, a recent study has demonstrated significant advantages of using skeletal muscle for the delivery of MSC. While skeletal muscle has been used as a delivery route for myopathic, neurodegenerative, and vascular diseases, these studies have identified 3 main advantages of skeletal muscle MSC delivery.
Research has identified two key factors that profoundly affect observed dwell-time variations of 72 hours to 8 months observed in MSCs transplanted in the skeletal muscle; these factors include immune rejection and the methods used for MSC detections. Considering this, the authors point out that allotransplantation provides an advantage since MSCs exhibit low immunogenicity and are expected to evade the immune system.
Although little information on the IM delivery of MSCs currently exists, previously conducted clinical trials demonstrated no therapeutic advantage of using higher doses of MSCs; other studies demonstrated medium doses of MSCs to be more effective than either a lower or higher dose.
While IM-delivery has been shown to be clinically safe and increases the longevity of the secretory activity of the delivered cells, the authors point out that it is important to further evaluate the fate of MSCs post-delivery in skeletal muscle.
Ankylosing spondylitis (AS) is a chronic and progressive inflammatory disease that primarily affects the sacroiliac joints and the spine; in rare cases, AS can also cause issues for the peripheral joints and extra-articular organs, including the skin, eyes, and cardiovascular system.
While there are a number of drugs prescribed to treat symptoms associated with AS, there is currently not a cure for AS nor is there a non-pharmaceutical method for treating the condition and its symptoms.
Considering the potent immune-modulated activity and their ability to inhibit B cell differentiation, T cell activation, and proliferation, researchers have increasingly been exploring the use of mesenchymal stem cells (MSCs) as a potential treatment option for a number of autoimmune diseases.
In this current study, Li et al. evaluated the therapeutic effects of umbilical cord MSC (uMSC) transplantation in patients with AS. This review summarizes the authors’ findings.
Specifically, Li et al.’s study evaluated 5 patients with AS after receiving intravenous transfusions of uMSCs.
After receiving an intravenous uMSC transfusion, the authors reported lower levels of inflammation, slowed progression of AS, and reduced levels of ESR, CRP, and other specific markers indicative of improved spinal functions and spinal movement in subjects with AS.
Considering these findings, the authors conclude that uMSC transplantation is feasible and safe and induces limited side effects.
The authors of this study also highlight a number of limitations, including the low number of patients, limited statistical analysis, and lack of a control group that did not receive an infusion.
In light of these results, Li et al. call for future studies using a larger cohort of patients with AS to enable the systematic evaluation of uMSC in treating symptoms of AS.
Mesenchymal stem/stromal cells (MSCs) continue to be viewed as a source of cell therapy applications due to their immunomodulatory and anti-inflammatory effects and because of their ability to stimulate angiogenesis. In MSCs, these benefits are mainly attributed to the secretion of factors.
Despite MSCs’ known and favorable proliferation levels, multipotency, and immune response regulation, there are other important variables that should be considered when developing cell therapy applications, including the source of MSCs.
Considering that MSCs collected from different tissues can form heterogeneous cellular populations and manifest tissue-specific functional differences, the source of MSCs should be of primary consideration when developing new therapeutic approaches.
In this review, Paladino et al. present a review of recent research related to the therapeutic application of Wharton’s jelly MSC (WJ-MSC) harvested from umbilical cords and how these cells affect immune responses in comparison with other sources of MSCs.
Bone marrow-derived stem cells BM-MSCs have long been considered the favored source of MSCs and are the most used source of MSCs in clinical research. However, BM-MSCs have a history of showing mixed results and are not always recommended for use due to the invasive and painful process used to obtain the MSCs.
While other alternative sources, including adipose tissue, dental pulp, and menstrual blood, are available, WJ-MSCs are considered an easily accessible source of MSCs that are comparable to BM-MSC and have suffered less environmental interference and demonstrate higher proliferative capacity than other sources.
Studies using WJ-MSC in this capacity have shown their robust immunomodulatory potential. Specifically, the authors of this review reference a number of studies using various sources of MSCs, including WJ-MSCs that demonstrate immunomodulatory potential similar to other MSC sources. Studies also demonstrate that WJ-MSC is a better suppressor of specific inflammatory factors, including mixed lymphocyte reaction, and possesses higher levels of IL-17A (a key mediator in the treatment of graft-versus-host disease) than MSCs collected from other sources.
Paladino et al. conclude that the available literature indicates that WJ-MSCs possess immunological features comparable to MSCs from other sources, including bone marrow-derived MSCs. The authors also call for further study to identify the best therapeutic indications for WJ-MSCs as a substitute for other sources of MSC, including BM-MSC.
Currently, 1 in every 4 adults suffer from chronic knee pain; this represents a 65% increase over the last 20 years. While knee pain can be caused by several causes, including meniscus tears, tendinosis, sprains, rheumatoid arthritis, and lupus, osteoarthritis (OA) remains the most common contributor to this condition.
In this study, Lee and Padgett evaluate the use of the peptides BPC157 and thymosin-beta-4 (TB4) for the treatment of knee pain. Specifically, as part of this study, 17 patients received peptide therapy consisting of BPC157 or a combination of BPC157 and TB4 injections for their knee pain.
It is estimated that the human body has nearly 300,000 peptides. These peptides consist of chains of amino acids that range from 2 to 100 amino acids in length. One specific peptide, BPC157, when isolated, has demonstrated restorative properties that have helped in the repair of tendons, ligaments, muscles, nerves, and bone fractures. BPC157 has also been found to promote recovery from traumatic brain injury (TBI), reduce blood clots, and protect the liver.
Because of its reported acceleration of recovery from ruptured tendons, BPC157 has also become a favored therapeutic option by athletes looking to speed up the healing of their injuries. Prior to this study, no study using BPC157 in humans has been published, nor has this peptide received US Food and Drug Administration (FDA) approval in the United States.
TB4 is FDA-approved and a naturally occurring peptide that originates in the thymus gland. TB4 possesses a range of healing and regenerative properties, including accelerating recovery from skin wounds, TBI, stroke, and multiple sclerosis. TB4 has also been shown to reduce inflammatory markers and pain.
The patients involved in this study either received only an intra-articular injection of BPC157 or a combination of both BPC157 and TB4 injections.
As a follow-up, and as part of this retrospective study, the author followed up with patients between 6 months and 1 year after receiving peptide injections in their knee. Of those receiving only the intra-articular injection of BPC157, 91.6% reported significant improvements in knee pain while 75% of patients who received both peptides showed significant improvement.
While treating knee pain with BPC157 and TB4 has demonstrated potential for future therapeutic options, the author calls for additional larger studies to better understand improvements in structural changes and increased collagen production in patients with OA-induced knee pain.
Lee concludes that this retrospective study demonstrates that BPC157 has been shown to help reduce knee pain and have prolonged effects lasting over six months, a significant benefit when compared to the documented short-lived results of steroid treatment. Source: “Intra-Articular Injection of BPC 157 for Multiple Types of Knee Pain.” https://pubmed.ncbi.nlm.nih.gov/34324435/.
Liver disease accounts for nearly two million deaths annually and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately two-thirds of all liver-related deaths occur in men.
Most forms of chronic liver disease result from viral infections, alcohol abuse, or metabolic disorders and eventually result in cirrhosis and liver failure. The only effective treatment for end-stage cirrhosis is liver transplantation. Unfortunately, considering organ shortages and the high cost associated with this type of medical procedure, liver transplants are not available in many countries.
As part of this review, Kang et al. discuss the therapeutic effects of MSCs in liver diseases to address questions regarding their efficacy and safety, evaluate recent advances in this area, and consider the potential risks and challenges in the use of MSC-based therapies for liver disease.
When considering the therapeutic effects of MSC therapy in chronic liver disease, the authors conclude that this treatment has shown to be effective, primarily due to their immunomodulation, differentiation, and antifibrotic properties exhibited by MSCs. The authors also point out that although the safety and therapeutic effects of MSC therapy have been observed in several clinical studies, to date the therapy has demonstrated only modest improvements in treating liver disease. Kang et al. attribute this modest improvement, in part, to the current limited feasibility of transplanted cells.
The authors provide a detailed review of the strategies that have been utilized to improve the effects of MSC transplantation, including tissue engineering, preconditioning, genetic engineering, and using extracellular vesicles as cell-free therapy, and summarize the future potential of each of these as ways to improve MSC transplantation.
Kang et al. also highlight several problems that must be considered and addressed before MSCs are fully accepted as clinical therapeutic treatment options for chronic liver disease; these problems include the potential for carcinogenesis and viral transmission. For example, previous animal studies have demonstrated a relationship between the development of sarcoma and the number of passages. While this has not been directly observed in clinical trials involving human MSCs, the follow-up period was too short to allow for observed evidence of this development. As a result, the authors call for a detailed study into the chromosomal integrity before MSC transplantation to ensure the safety of the procedure.
In addition to the potential for tumor cell growth, allotransplantation of MSC cells may involve the risk of viral transmission to the patients. As a result, the authors indicate that both MSC recipients and donors may need to be screened for the presence of specific viruses, including parvovirus B19, herpes simplex virus, and cytomegalovirus.
The authors conclude that the prospects of MSC-based cell therapy for treating chronic liver disease will be determined by standardizing the cell source, culture conditions, administration route, and the outcomes of future large-scale clinical trials.
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