by admin | Sep 3, 2021 | Stem Cell Therapy, Mesenchymal Stem Cells, Stem Cell Research
Human mesenchymal stem cells (hMSCs) are multipotent adult stem cells found in tissue throughout the body, including in the umbilical cord, bone marrow, and adipose tissue. Capable of self-renewing and differentiating into multiple tissues including bone, cartilage, muscle, fat cells, and connective tissue[1], MSCs appear to have a wide range of potential for use as therapeutic purposes for many serious health problems occurring throughout the body.
In this review, Rodriguez-Fuentes et al. examined currently registered (as of July 2020) clinical trials involving mesenchymal stem cells with the goal of analyzing the different applications of MSCs in a clinical setting to demonstrate the growing and broad potential of their therapeutic application relative to the reconstruction of damaged tissue.
As of July 2020, the authors identified 1,138 registered clinical trials (CTs) worldwide using MSCs to investigate their therapeutic potential. Therapeutic applications are a relatively new area of study, evidenced by the fact that only 19 CT studies were started between 1995 and 2005 and over 900 were initiated in the last ten years (2011-present). The majority of these CTs focused on the fields of traumatology, neurology, cardiology, and immunology. Interestingly, of the 1,138 CTs identified in this query, only 18 had published outcomes.
Examining the global distribution of registered CTs, it was observed that CTs are located in 51 countries, with China (228) and the US (186) leading the research.
As part of this review, and in addition to examining the number and geographic locations of registered CTs, the sourcing, isolation and treatment methods, and storage conditions of MSCs used in each clinical trial.
Most of the MSCs used for these CTs were obtained from cells of the iliac crest, placenta, and adipose tissue. All recovered cells underwent steps of purification and expansion prior to use in patients. Additionally, all methods used in these CTs were also found to follow good manufacturing practices (GMP).
Upon completing their review of registered CTs, Rodriguez-Fuentes et al. also observed that medical specialties for the most published studies included (in descending order) cardiology, traumatology, pneumology, neurology, hematology, ophthalmology, and plastic surgery. The most frequent pathologies addressed in these published CT studies included knee osteoarthritis, ischemic heart disease, and dilated cardiomyopathy. While the number of MSCs used varied by study, most utilized around 100 million MSCs.
The authors concluded that most studies analyzed as part of this review demonstrate positive outcomes with no serious adverse effects. While China and the US lead the world in the number of registered MSC clinical trials, the authors point out the fact that many of these CTs have multiple locations in different countries – indicating the importance of, and willingness to, collaborate internationally on this research.
Although most of the conditions for which clinical utility of MSCs have been published are conditions that do not currently have specific treatments with desirable or effective outcomes, there appears to be significant and broad potential for the clinical use of hMSCs without serious adverse events.
While there are currently at least 1,138 registered MSC CTs, there is still much to be examined and understood about MSCs. As such the continually increasing number of CTs including MSCs will help identify and demonstrate the therapeutic potential of these versatile stem cells.
[1] “Mesenchymal stem cells – Latest research and news | Nature.” https://www.nature.com/subjects/mesenchymal-stem-cells.
Source: Mesenchymal Stem Cells Current Clinical Applications. From https://www.sciencedirect.com/science/article/pii/S018844092030638X
by admin | Aug 6, 2021 | Stem Cell Therapy, Mesenchymal Stem Cells, Stem Cell Research
It is estimated that over 126 million Americans, or nearly one in two adults, are affected with some form of musculoskeletal disorder, condition, or injury – a number comparable to the percentage of the population currently living with a chronic lung or heart condition[1].
While there are a number of treatment modalities proven to be effective for treating musculoskeletal disorders, conditions, and injuries, using stem cells appears to be among the most explored promising potential option of these methods.
With mesenchymal stem cells (MSCs) being the preferred source of stem cell, mostly because of their abundance (including sources such as bone, tendon, skin, and blood) and ability to differentiate to many different tissues, orthopedic surgeons have focused largely on MSC therapies for healing a number of specific orthopedic conditions, including the healing of fractures, regenerating articular cartilage in degenerative joints, healing ligaments or tendon injuries, and replacing degenerative vertebral discs.
The goal of the comprehensive literature review conducted by Akpancar et al. was to evaluate the most recent progress in stem cell procedures and current indications in the orthopedic clinical care setting.
Specifically, as part of this review, the authors found that therapeutic applications using stem cells, and MSCs in particular, allow the stem cells to be used as progenitor cells as a way to enhance the healing and repair process. The authors point out that while many sources of stem cells have been considered for use in orthopedic procedures, including bone marrow-derived MSCs (BM-MSCs), adipose-derived stem cells (AD-MSCs), synovial tissue-derived stem cells (ST-MSCs), peripheral blood-derived progenitor cells, and bone marrow concentrate, the optimal source of stem cells has yet to be determined.
In addition, Akpancar et al. while reviewing the orthopedic indication of stem cells on various musculoskeletal disorders, conditions, and injuries, found that in large part, stem cell therapy demonstrated positive results in improved healing in a variety of orthopedic indications, including major orthopedic bone-joint injuries, osteoarthritis-cartilage defects, ligament-tendon injuries, as well as other conditions.
Despite these findings, the authors also point out that while there have been large amounts of preclinical studies conducted and there continues to be increasing interest in performing additional studies on human subjects, the current findings gathered from preclinical studies are still preliminary. Considering this, the authors recommend additional research be conducted to evaluate the safety and efficacy of stem cells therapy in orthopedic surgery.
Source: (2016, August 16). The Current Perspectives of Stem Cell Therapy in Orthopedic Surgery. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253188/
[1] “One in two Americans have a musculoskeletal condition: New report ….” 1 Mar. 2016, https://www.sciencedaily.com/releases/2016/03/160301114116.htm.
by admin | May 14, 2021 | Stem Cell Therapy, Mesenchymal Stem Cells, Stem Cell Research, Traumatic Brain Injury
According to the CDC, in 2019, traumatic brain injury (TBI) contributed to nearly 61,000 deaths in the United States alone[1]. While there are several clinical treatments designed to address the neurological dysfunction after sustaining a TBI, including hyperbaric oxygen, brain stimulation, and behavioral therapy, none appear to produce satisfactory or lasting results.
In recent years, several studies have demonstrated the therapeutic potential of various stem cells, including mesenchymal stem cells (MSCs), neural stem cells (NSCs), Multipotent adult progenitor cells (MAPCs), and endothelial progenitor cells (EPCs) in the treatment of neurological impairment resulting from TBI. Specific benefits of these stem cells observed throughout these studies demonstrate that exogenous stem cells have the ability to migrate to the site of damaged brain tissue, help to repair damaged tissue, and significantly improve neurological function.
In this article, Zhou et al. review recent findings on the role, effects, deficiencies, and related mechanisms of the various stem cells being used as therapeutic agents in the treatment of TBI.
Examining numerous studies occurring between 2010-17 and exploring various TBI models and the roles of different stem cells in animal models, the author’s general summary is that the use of stem cells demonstrated some form of measurable improvement in every study reviewed. As a reference, specific observed benefits included improved integrity of the blood-brain barrier; improved neurological function, social interaction, and motor performance; enhanced neurovascular repair and recovery; and enhanced cognitive and spatial learning, information retention, and memory retrieval.
The authors point out that although there appears to be a large amount of research exploring the complexity of pathophysiology and the application of stem cell therapy for treating TBI, many problems still exist and must be addressed before the best method for TBI recovery can be determined.
Specifically, while there have been several clinical studies exploring the role of stem cells in the role of TBI treatment and recovery, and while most demonstrate promising results, the studies have almost universally been completed on mice and/or rats, contained human sample sizes that are not large enough, or failed to include a control group. As a result, Zhou et al. call for further study, including multi-center long term follow-up and randomized prospective trials that examine the safety of stem cells, route of injection, the time of injection, and the specific mechanisms as a way to identify the appropriate and effective stem-cell-based therapeutic treatment options for those suffering from various types of TBI.
Source: (2019, August 13). Advance of Stem Cell Treatment for Traumatic Brain Injury. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700304/
[1] (2021, May 12). Get the Facts About TBI | Concussion …. Retrieved from https://www.cdc.gov/traumaticbraininjury/get_the_facts.html
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 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 | Apr 2, 2021 | Stem Cell Therapy, Mesenchymal Stem Cells, Osteoarthritis, Stem Cell Research
Osteoarthritis (OA), the most common form of arthritis, affects over 32 million people in the U.S. each year. Characterized by a progressive degeneration of cartilage resulting in pain, stiffness, and swelling in the joints, and most frequently occurring in the hands, hips, and knees, OA has no pharmacological, biological, or surgical treatment to prevent progression of the condition. The authors of this case report focus specifically on potential treatment options for OA of the knee.
With the emergence of stem cell-based therapies for a multitude of health conditions, stem cells, and specifically mesenchymal stem cells (MSCs), have demonstrated immunosuppressive activities that could prove beneficial in supporting the regeneration of cartilage tissue in and around joints in the body.
Research has demonstrated that MSCs are effective in differentiating into essential connective tissues like fat, cartilage, and bone; MSCs have also demonstrated immunomodulatory and anti-inflammatory effects, the ability to self-renew, and plasticity, making MSCs a potentially powerful treatment of OA in the knee (and other parts of the body).
This specific case study details cartilage regeneration in the knee of a 47-year-old woman diagnosed with OA when treated with bone marrow-derived MSC cells. For the course of this treatment, autologous MSCs were collected from bone marrow harvested from the iliac crest. After processing and preparing the MSCs, the sample was confirmed to be free of microbial contamination and was prepared and transplanted into the patient’s knee joint.
Periodic follow-ups with the patient revealed no local or systemic adverse events associated with the MSC transplant procedure. The authors of this case report found that the patient’s functional status of her knee, the number of stairs she could climb, reported pain on a visual analog scale, and walking distance all improved in the two months following the MSC transplant procedure.
Additionally, twelve months after the transplant, the patient demonstrated a positive change in WOMAC (3 to 2), a continued increase in the number of stairs climbed (5 increasing to 50), and visual analog (80 mm to 11 mm). The patient also demonstrated improved gelling (or the amount of time it takes for synovial fluid to thicken as a result of rest) in the knee from 8 minutes to 30 minutes; knee flexion also increased 20° (100° to 120°). Periodic MRIs taken after the transplant procedure demonstrated an extension of the repaired tissue over the subchondral bone.
Mehrabani, et al. conclude that MSC transplantation for treating OA in the knee appears to be a simple, safe, effective, and reliable treatment option that has demonstrated pain relief, improved quality of life, and significantly improved quality of cartilage without hospitalization, pharmaceuticals, or surgery.
Source: (n.d.). The Healing Effect of Bone Marrow-Derived Stem Cells … – NCBI – NIH.; from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003953/
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