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 | 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 | Jun 18, 2021 | Stem Cell Research, Glaucoma, Stem Cell Therapy
Characterized by vision loss caused by progressive damage to the optical nerve, glaucoma continues to be the second leading cause of blindness worldwide. Although painless, the glaucoma-induced cupping, thinning, and structural damage caused to various parts of the eye causes vision loss that starts in the periphery and gradually travels inward, eventually resulting in a total loss of vision.
Current treatments for glaucoma are mainly pharmacologic, laser-based, and surgical procedures that reduce the eye’s intraocular pressure (IOP), the most treatable risk factor of glaucoma. While these treatments have been demonstrated to be effective in treating the symptoms associated with glaucoma, they are not able to restore vision that has already been lost as a result of glaucoma.
The purpose of Chamiling et al.’s review is to evaluate the current developments surrounding the use and effectiveness of stem cell therapy, not only to treat the symptoms of glaucoma and other optic neuropathic conditions but also to explore the potential of restoring vision loss resulting from these conditions.
According to the authors, while most glaucoma-based therapies center around controlling IOP, they fail to address the main contributing factors associated with glaucoma-associated vision loss – which include axonal damage and loss of retinal ganglion cells (RGCs), the neurons that make up the optical nerve and that are responsible for transmitting visual images from the eye to the brain.
In their natural state, RGCs are what’s considered postmitotic; in other words, they are cells that do not regenerate. This means that any vision loss sustained as a result of the loss of these RGCs is permanent and unable to be reversed. Adding to the severity of early glaucoma is the fact that significant damage to, and loss of, RGCs typically occur before the first signs of developing visual issues are detected.
However, with the recent advancements in cell-based therapies, and considering the field’s rapid-developing understanding of ocular regeneration, there is hope that science will soon be able to advance options that not only treat glaucoma but also restore vision lost as a result of the condition. As such, Chamiling et al. focus this review primarily on the use of stem cell-derived RGCs for drug discovery and transplantation-based therapy in four specific areas: control of intraocular pressure; using pluripotent stem cells as a source of RGCs; stem cell-derived RGCs for transplantation and vision restoration; and using stem cell as a source for neurotrophic factors (NTF).
Through their review of the literature and, in part, a summary of advanced discussions held at the 2015 Ocular Research Symposia Foundation’s “Sight Restoration Through Stem Cell Therapy” meeting, the authors conclude that advancements in our understanding of stem cells combined with key advancements made in the field of ocular biology have resulted in the ability to differentiate human stem cells into a number of different ocular cell types.
While much of the research and trials examined has involved animal models of study, the progression of these efforts has led to a number of human trials exploring the differentiation of stem cells into retinal pigment epithelial cells. In addition, and more specifically related to glaucoma, recent studies demonstrate significant potential for the differentiation of stem cells into trabecular meshwork (TM) and RGCs as well as the opportunity to be used as a way to secrete NTFs.
As a result of this review, Chamling et al. call for continued study into the potential of human stem cells for the treatment of glaucoma while also concluding that the rapid advancement in stem cell technology continues to provide the pathway to further understanding of stem-cell applications in this field and to offer new hope for using cell-based therapies as a way to restore vision lost as a result of glaucoma or other optic nerve conditions.
Source: (2016, April 1). The Potential of Human Stem Cells for the Study … – PubMed – NIH, from https://pubmed.ncbi.nlm.nih.gov/27116666/
by admin | Jun 4, 2021 | Stem Cell Therapy, COPD, Stem Cell Research
For patients facing a lung disease, including COPD, current and traditional therapeutic options may not be as effective in managing symptoms or slowing the progression of the condition so researchers have turned their attention to the potential benefits of stem cell therapy and ex vivo lung bioengineering in hopes of developing new and effective therapeutic approaches to treat lung disease.
Demonstrating a rapid progression over the last decade, the development of stem cell therapies and bioengineering approaches for lung disease has primarily shifted focus to the application of immunomodulatory and paracrine actions of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) and the field of ex vivo lung bioengineering.
In this manuscript, Weiss reviews clinical trials in lung disease and provides the current progress for a variety of therapeutic options. Specific treatments reviewed include:
- Structural Engraftment of Circulating or Exogenously Administered Stem Cells
- Ex Vivo Derivation of Lung Epithelial Cells from Embryonic Stem Cells or Induced Pluripotent Stem Cells (iPS)
- Endogenous Lung Stem and Progenitor Cells
- Circulating Fibrocytes
- Endothelial Progenitor Cells
- MSCs and Immunomodulation of Lung Disease
The author points out that although preclinical literature supports the use of EPCs and MSCs in acute lung injury and/or chronic inflammatory and immune-mediated conditions (including asthma, bronchiolitis, obliterans, and bronchopulmonary dysplasia), these preclinical models are not always predictive of clinical behaviors. As such, clinical investigations of these cell-based therapies for lung disease have been slow to develop.
Currently, the only effective treatment for severe lung diseases, including BPD, CF, COPD, and IPF, is lung transplantation. With a 50% five-year post-transplant mortality rate, essential lifelong immunosuppression (to prevent chronic lung rejection), and a critical shortage of donor’s lungs, research has turned its attention toward manufacturing surgically implantable ex vivo (or “outside the living body”) lung tissue. While several challenges still exist, recent significant progress has been made using both synthetic and donor tissue in generating ex vivo tissue for use in various lung treatment applications.
The author concludes that while exciting progress has been made in the field of stem cell therapy and ex vivo generation of tissue to treat lung diseases, much research is still on the horizon. Within future research, they hope to better understand the identity of endogenous lung airway, the development of functional airway and alveolar epithelial cells from ESCs and iPS cells, and a better understanding of the physiologic and pathophysiologic roles of EPC and Fibrocytes in lung diseases.
The use of stem cell therapy and ex vivo lung bioengineering offers tremendous potential for the treatment of lung diseases, however, the clinical use of artificial engineered or decellularized scaffolds for use in treating lung disease is likely to be several years off.
Source: (n.d.). Current Status of Stem Cells and Regenerative Medicine in Lung …. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208500/
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 | 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/.
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