by admin | Jul 30, 2021 | Stem Cell Research, Multiple Sclerosis, Stem Cell Therapy
Typically understood to support hematopoiesis and to produce the cells of the mesodermal lineage, mesenchymal stem cells (MSCs) found in bone marrow, fat, and other tissues of the body, have recently been found to contain additional properties that include immunomodulator and neurotrophic effects.
Considering earlier studies that have demonstrated favorable effects of MSC treatments in a variety of conditions – including stroke, multiple sclerosis, multi-system atrophy, and amyotrophic lateral sclerosis, Petrou et al. performed this double-blind study as a way to evaluate the best way of administration and the safety and clinical efficacy of MSC transplantation – specifically in patients with active and progressive multiple sclerosis.
The response of the 48 patients with progressive multiple sclerosis and with displaying evidence of either clinical worsening or activity during the previous year in this study were evaluated after being treated intrathecally (IT) or intravenously (IV) with autologous MSCs or with sham injections. Having identified a critical and unmet need for treatment, the goal of Petrou et al.’s study was to examine the therapeutic efficacy of MSC transplantation in this specific population.
Over the course of this controlled clinical trial, participants were randomly assigned to three treatment groups and treated (either intrathecally or intravenously) with autologous MSCs or with sham injections. At the 6-month mark, the authors of this study retreated half of the patients in both the MSC-IT and MSC-IV groups with MSCs, while the remaining participants were treated with sham injections. The same process occurred with patients initially treated with sham injections; meaning that at the 6-month mark, half were either treated with MSC-IT or MSC-IV.
Prior to the start of this study, Petrou et al. established a number of primary and secondary endpoints. Predetermined primary endpoints of this study included: the safety of the MSC-IV and MSC-IT treatments and the difference among the three groups in relation to performance on the Expanded Disability Status Scale (EDSS) at 6- and 12-month intervals. Predetermined secondary endpoints included the difference between the sham-treated and MSC-IT or MSC-IV treated group in the number of relapses and the relapse rate, the number of MRI gadolinium-enhancing lesions, the annualized rate of change in the T2 lesion load on MRI, percent brain volume change, performance on a series of physical and cognitive functions, and the retinal nerve fiber layer thickness.
At the conclusion of this 14-month trial, the authors reported that the study demonstrated positive results in all predetermined primary endpoints. More specifically, throughout the course of this study, the authors discovered that significantly fewer patients experienced treatment failure in the MSC0IT and MSC-IV groups compared with those in the sham-treated group. Additionally, over the course of the following year, nearly 59% and 41% of patients treated with MSC-IT and MSC-IV exhibited no evidence of multiple sclerosis activity; this is compared with less than 10% of patients in the sham-treated group.
Significant improvements of those receiving MSC-IT treatment (compared to sham treatment) were also observed in the following: ambulation index, the sum of functional scores, 25-foot timed walk test, 9-hole peg tests, PASAT and OWAT/KAVE cognitive tests, and newer biomarkers, including retinal nerve fiber layer and motor network. The authors also report beneficial, but less significant effects were observed in the MSC-IV groups.
Although the authors report a number of limitations associated with this study, including a small number of patients in each group, the short duration of the study, and the crossover design of the study (which could have resulted in a “carry-over” effect from the first cycle of treatment), they also conclude that the clinically significant findings observed in patients with progressive multiple sclerosis who were previously unresponsive to traditional or conventional therapies provide clear evidence of short-term efficacy and possible indications of neuroprotection induced by administration of autologous MSCs in patients with progressive multiple sclerosis.
In addition, the authors found that intrathecal administration of MSCs appears more beneficial than intravenous, as well as the potential benefits provided by receiving repeated injections of MSCs.
As such, Petrou et al. conclude by calling for a larger phase III study to confirm these findings and as a way to further evaluate the therapeutic potential of autologous MSCs in neuroinflammatory and neurodegenerative diseases, including active progressive multiple sclerosis.
Source: (2020, December 1). Beneficial effects of autologous mesenchymal stem cell … – PubMed. from https://pubmed.ncbi.nlm.nih.gov/33253391/
by admin | May 7, 2021 | Stem Cell Therapy, Mesenchymal Stem Cells, Musculoskeletal
Research exploring the benefits of mesenchymal stem cells (MSCs) has demonstrated tremendous potential as a regenerative therapy option for the musculoskeletal system. Research into these cell-based regenerative therapies is promising, and they must continue to provide the data necessary to show their therapeutic potential in clinical settings.
In this review, Steinert et al. review and summarize some of the promising and unique therapeutic features of adult MSCs, detail their current state of clinical application as a regenerative musculoskeletal therapy, and describe the potential for future developments in this field.
Specifically, as a part of this review, the authors share the status of 31 clinical cell therapies for musculoskeletal regeneration occurring between 1996 through 2011 and specifically covering bone defects and nonunions, avascular necrosis of the hip, cysts and benign tumors of the bone, cartilage lesions, and tendons and ligaments; results for the majority demonstrate the safety of and/or the efficacy associated with the specific method of cell-delivery being evaluated.
The field of regenerative orthopedics points to the large body of MSC clinical research indicating the successful treatment of myocardial infarction, post-stroke or spinal cord injury nerve regeneration, graft versus host disease, and a variety of other conditions as an indication that the application has tremendous potential as a regenerative therapeutic option in a wide variety of musculoskeletal indications.
Although there appears to be evidence demonstrating the paracrine and trophic functions of MSCs, research explaining the specifically demonstrated therapeutic effects is still being determined. The authors highlight that research continues to explore the reasonable therapeutic expectations associated with MSC-based treatments, an essential step required to fully understand the range of healing associated with musculoskeletal regenerative cell-based therapy.
The authors, in concluding this review, point out that the demand for MSC-based musculoskeletal regenerative therapies continues to increase. Steinert et al. call for further study into the specific combination of cell preparation, bioactive factors, and stimuli for each specific MSC therapeutic application. Once these have been demonstrated for each application and should they demonstrate better or improved outcomes compared to standard treatments, only then can they be considered for long-term clinical application.
Source: (n.d.). Concise review: the clinical application of mesenchymal stem cells …. Retrieved from https://pubmed.ncbi.nlm.nih.gov/23197783/
by admin | Apr 30, 2021 | Neurodegenerative Diseases, Stem Cell Research, Stem Cell Therapy
Neurodegenerative disease is a broad term encompassing a number of chronic, progressive diseases that result in degeneration and or death of neurons; these diseases include Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS) and affect over 50 million Americans each year[1][2].
Since neurons possess a very limited ability to reproduce and/or replace themselves, any damage to these cells tends to be permanent and contributes to incurable and progressive debilitating conditions affecting physical movement and mental function.
While research has determined that these neurodegenerative diseases are primarily a result of the accumulation of misfolded proteins in the brain, the specific cause of these conditions remains unknown; additionally, the complexity of these conditions often lead to delayed diagnosis, most often a result of the lack of effective and recognizable biomarkers. To date, no preventative treatment for these conditions exist and any current treatment serves to only delay the progression of the disease, most often with poor results.
In this article, Yao et al. explore the viability of using mesenchymal stem cells (MSCs) as cell replacement therapy for treating neurodegenerative diseases. According to the authors, MSCs demonstrated the ability to self-renew and differentiate coupled with their relative ease of collection, isolation, and ability to culture and their immunoregulatory properties make them a promising potential treatment option.
Although the specific therapeutic mechanisms of MSCs in the treatment of neurodegenerative diseases are still being studied, they have shown potential in three specific areas: homing, paracrine, and immunoregulation.
Homing involves MSCs ability to spontaneously migrate to damaged regions of the body, making them a viable therapeutic treatment option – especially as a carrier of therapeutic drugs. It is hypothesized that MCS’s ability to home should allow drugs to be attached and to pass through the blood-brain barrier to be delivered to locations in the CNS and brain that are affected by neurodegenerative diseases.
Paracrine, or paracrine signaling, is a cell’s ability to release hormones that communicate with the cells in its vicinity. MSCs ability to secrete growth factors, cytokines, chemokines, and various enzymes are important aspects of cell migration and immune regulation. Animal studies have demonstrated using MSC-derived exosomes to improve symptoms associated with muscle atrophy translates into a promising clinical treatment strategy for neurodegenerative diseases.
MSCs are undifferentiated precursor stem cells with low immunogenicity. Researchers attribute the immunoregulation of MSCs to their various interactions with T cells, B cells, and natural killer cells. Animal studies have shown that placental-derived MSCs have demonstrated beneficial effects, particularly in mice with AD; researchers hypothesize that this effect is a result of these MSCs inhibiting the release of inflammatory cytokines, preventing cognitive impairments, and increasing the survival rate of neurons and nerve regeneration. These findings have demonstrated the potential for immunosuppressants, in combination with MSCS, to be used in future clinical treatments of neurodegenerative diseases.
After reviewing numerous in vitro and in vivo experiments in animal models, the researchers have confirmed the potential therapeutic benefits of MSCs as well as their safety and effectiveness in a wide variety of therapeutic applications. Additionally, studies have also demonstrated no serious or concerning adverse reactions associated with clinical trials (both human and animal) using MSCs from autologous or allogeneic sources.
However, Yao et al. caution that as therapies using MSCs continue to develop, so too should the process used for preparing MSCs as well as that used for determining ideal method and dose for patients; taking these steps will contribute to a deeper understanding of MSCs potential when used as a therapeutic treatment for neurodegenerative diseases.
Source: (2020, July 20). Mesenchymal Stem Cells: A Potential … – Karger Publishers. Retrieved from https://www.karger.com/Article/Fulltext/509268
[1] “What? | JPND.” https://www.neurodegenerationresearch.eu/what/.
[2] “Neurodegenerative Diseases: An Overview of … – NCBI – NIH.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280411/.
by admin | Apr 9, 2021 | Mesenchymal Stem Cells, Spinal Cord Injury, Stem Cell Research, Stem Cell Therapy
Spinal cord injury (SCI) continues to be a significant cause of disability. In fact, it is estimated that annual SCIs account for nearly 18,000 injuries in the United States and between 250,000 and 500,000 injuries worldwide[1]. Additionally, an estimated 294,000 people in the United States are currently living with some form of SCI, with males accounting for nearly 80% of all SCI injuries[2].
Despite a large number of SCIs occurring each year, therapeutic treatment options remain limited and primarily ineffective. Recently, improvements in the understanding of the promising role stem cells play in the healing process have led to significant developments in improving healing and restoring function lost as a result of Spinal Cord Injuries; specifically, the therapeutic treatment of SCIs with mesenchymal stem cells (MSCs) in animal models has demonstrated promising results.
Building off of the success observed in previous studies, Honmou Et al.’s recent study (2021) sought to further explore the safety and feasibility of intravenous infusion of MSCs is SCI patients; the study also explored the patients’ functional status after receiving IV infusion of MSC.
Specifically, Honmou Et al.’s phase 2 study delivered a single infusion of autologous MSCs cultured in auto-serum, to 13 SCI patients. After infusion, the study assessed the feasibility and safety of this procedure over a six-month period by using the American Spinal Injury Association Impairment Scale (ASIA) and International Standards for Neurological Function Classification of Spinal Cord (ISCSCI-92). The researchers also used the Spinal Cord Independence Measure (SCIM-III) as a way to assess the ability of daily living after receiving MSCs infusion.
Although this was a small, early, unblinded, and uncontrolled study, the researchers point out that the intravenous infusion of autologous bone marrow-derived MSCs, expanded in auto-serum, into SCI patients appeared to be safe and feasible with none of the patients exhibiting abnormal cell growth or neurological deterioration. Additionally, and similar to what’s been observed in prior studies conducted on animal models, the findings appear to support the rapid improvement of neurological function within a few days after IV infusion. The researchers also pointed out this study had several limitations, including potential observer bias and potential improvements resulting from surgical interventions.
The researchers point out that although the specific mechanism for this observed improvement in neurological status is not clear, several studies suggest that secreted neurotrophic factors from MCSs might be associated with the rapid improvements. Additional studies have also demonstrated that IV infusion of MSCs in patients with SCIs might also encourage changes in gene expression that encourage functional improvements, an observation that was consistent with the findings of this study.
In conclusion, the authors reiterate that the observed safety, feasibility, and initial indications of functional improvement after MSC infusion support the importance of additional, larger future studies designed to examine potential efficiencies in patients with SCI. Source: (2021, February 18). Intravenous Infusion of Auto Serum-expanded … – ScienceDirect.com. Retrieved March 23, 2021, from https://www.sciencedirect.com/science/article/pii/S0303846721000925#!
[1] “Spinal cord injury – WHO | World Health Organization.” 19 Nov. 2013, https://www.who.int/news-room/fact-sheets/detail/spinal-cord-injury.
[2] “(SCI) Facts and Figures at a Glance – National Spinal Cord Injury ….” https://www.nscisc.uab.edu/PublicDocuments/fact_figures_docs/Facts%202015.pdf.
by admin | Mar 12, 2021 | Stem Cell Therapy, Mesenchymal Stem Cells, Osteoarthritis
Affecting over 52 million people, or nearly 25% of the adult patients, osteoarthritis (OA) continues to be the leading cause of disability for people in the United States. Occurring as a result of the protective cartilage, or articular cartilage, that cushions the ends of the bones breaking down, OA can occur in any joint, but most often causes pain, stiffness, and swelling in the hands, feet, knees, hips, and lower back[1][2].
To date, current conventional treatments employing pharmacological treatments have been developed to temporarily address the symptoms (i.e.: relieve pain, stiffness, and swelling) of OA, but have proven ineffective in preventing the onset, progression, or long-term symptoms of the condition. While there are a number of reasons conventional OA therapies have demonstrated themselves to be ineffective, the primary reason is that they do not regenerate the cartilage required to prevent the progressive degenerative process associated with OA.
However, recent studies exploring mesenchymal stem cell-based therapy for OA have demonstrated several potential benefits, including regenerating lost cartilage, slowing cartilage degeneration, pain relief, and improved patient mobility.
Currently, there have been a number of advancements in using cellular-based therapy for OA, including techniques such as autologous chondrocyte implantation (ACI) and treatment with embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). While all of these treatments have shown promise in the regeneration of cartilage, each has its own issues which limit its effectiveness and/or availability.
Of the cellular based therapies being evaluated, none demonstrate as much promise, with so few drawbacks, as treatment of OA-related cartridge degeneration with mesenchymal stem cells (MSCs). Sourced from a variety of tissue, including adipose, bone marrow, and synovium, MSC have demonstrated to be progenitor cells with the ability to differentiate into cartilage. Because of this, coupled with the low-level of risk and ease of production, MSCs are considered to be a realistic option, holding the best potential treatment of OA.
While each requires further study, a number of studies, both animal and human, exploring the effectiveness of MSCs gathered from adipose tissue, bone marrow, and synovium have all demonstrated varying degrees of success related to regeneration of cartilage lost as a result of OA progression.
As a result of the benefits resulting from previous studies examining the role of MSCs as a cell-based treatment for treating OA-induced cartilage degeneration and because of the effectiveness and high cost associated with current pharmacological-based treatments, the authors of this review call for further clinical study into more innovative and effective modalities to demonstrate the efficacy, safety, and benefits of MSCs in treating patients with OA.
Article Source: (2016, August 10). Therapeutic potential of mesenchymal stem cell based therapy for …. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980326/
[1] “Osteoarthritis – Symptoms and causes ….” 22 Feb. 2020, https://www.mayoclinic.org/diseases-conditions/osteoarthritis/symptoms-causes/syc-20351925.
[2] “Osteoarthritis – Arthritis Foundation.” https://www.arthritis.org/diseases/osteoarthritis.
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