by admin | Jun 24, 2022 | Mesenchymal Stem Cells, Exosomes, Stem Cell Research, Stem Cell Therapy
Mesenchymal stem cells (MSCs) have been widely studied and increasingly recognized as a potential therapeutic with the ability to initiate and support tissue regeneration and remodeling. While over 1100 clinical trials have been conducted to assess the therapeutic benefits of MSCs, there continues to be widespread variation surrounding the potential treatment outcomes associated with these cells.
This review, authored by Chang, Yan, Yao, Zhang, Li, and Mao, focuses primarily on profiling the effects of the secretome, or the effects of paracrine signals of MSC, as well as highlights the various engineering approaches used to improve these MSC secretomes. Chang et al. also review recent advances in biomaterials-based therapeutic strategies for the delivery of MSCs and MSC-derived secretomes.
Recent research has demonstrated paracrine signaling as the primary mechanism of MSC therapeutic efficacy. This shift towards the MSC secretome in applications ranging from cartilage regeneration to cardiovascular and other microenvironments has demonstrated its therapeutic potential in prevalent injury models. Additionally, the versatility of MSCs allows them to be specifically tailored using biomaterials toward specific therapeutic outcomes.
A specific example of MSC secretome’s therapeutic potential is their ability to support cardiovascular tissue repair through minimization of fibrotic scarring of cardiac tissue typically observed to occur during a myocardial infarction (MI). Additionally, research has demonstrated MSC secretomes facilitate the proliferative, angiogenic, and anti-inflammatory phases of the wound healing process.
Secretome transfer occurring between MSCs and other cells in the target area primarily occurs through the release of extracellular vesicles (EVs) and is considered a safer form of therapeutic application compared to MSC therapy. MSC secretomes can also be specifically engineered through hypoxia, treatment with bioactive agents, and modulating cell-cell and ECM interactions in the MSC culture.
One of the biggest challenges facing the therapeutic efficacy of MSC is their limited cell survival, retention, and engraftment following injection or transplantation (found to be as low as 1% surviving one day after implantation). Recent studies have demonstrated MSC secretome, and specifically, EVs, although they remain a significant obstacle, are a promising alternative and able to bypass a number of cellular challenges, including cell survival.
Further consideration and approaches to increasing survival rates of MSCs include experimenting with a wide variety of biomaterials as a way to promote adaptation in the target implantation area. This includes looking for biomaterials to regulate oxygen tension levels, glucose supply, mechanical stress, and pH levels, which collectively can be used to regulate metabolic pathways of the MSC, effectively influencing cell survival and their ability to be used as therapeutic treatment options.
Despite the recent advances in the use of MSC secretomes and their delivery strategies, Chang et al. call for continued study of the subject and specifically recommend developing a specific set of paracrine cues to be used as a well-defined formulation in future therapeutic applications.
The authors also point out that the use of EVs and other direct applications of the MSC secretome are thought to be promising for the treatment of osteoarthritis, ischemic stroke, and coronavirus-related diseases. Considering this, Chang et al. highlight the increasing need to fully understand the paracrine signaling effects of MSC therapies and the delivery strategies associated with this application.
Source: “Effects of Mesenchymal Stem Cell‐Derived Paracrine Signals and ….” 12 Jan. 2021, https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.202001689.
by admin | May 20, 2022 | Stem Cell Therapy, Mesenchymal Stem Cells
Every year, stem cell therapy gains massive traction due to its incredible regenerative and auto-repair properties. More specifically, patients who deal with chronic, incurable conditions such as multiple sclerosis (MS) are closely following any news about this cutting-edge technology.
What is a stem cell?
A stem cell is a special biological entity that has unlimited differentiation potentials and can become any type of cell, hence is also called an undifferentiated cell. The body keeps a large number of these cells in different sites (e.g. bone marrow, umbilical cord, adipose tissue) in case it endures lesions that need regenerative capacities.
The fascinating feature of stem cells is their ability to differentiate into different cell types, including hepatocytes, nerve fibers, osteocytes, chondrocytes, and keratinocytes.
Are stem cells extracted from fetuses?
Perhaps the unethical aspect of stem cell therapy is the most commonly believed misconception out there. This is because early research focused on extracting stem cells from fetuses and embryos, which is what stuck with media outlets and the general population.
However, as mentioned earlier, stem cells are kept in the body to repair inflicted damage, allowing medical professionals to extract these cells and use them to manage a variety of conditions and their symptoms.
How do stem cells help with MS?
Multiple sclerosis is a chronic condition that’s caused by a type IV hypersensitivity reaction, which occurs when the immune system releases antibodies and specific cells to target a certain tissue. In the case of MS, the immune system attacks the myelin sheaths on nerve fibers that allow for fast bioelectrical transmissions of signals.
Stem cell therapy can potentially help MS progression and symptoms in two major ways:
Immunomodulating
By getting rid of the hyperactive immune cells and replacing them with new regulated ones, using stem cell therapy, the reaction against nerve fibers is potentially halted and symptoms may start to temper down.
Re-myelinization
Instead of targeting the immune system, stem cell therapy also helps by having the ability to regenerate myelin sheath. Note that the process of re-myelinization does not occur spontaneously without having progenitor cells to rely on.
In other words, if the patient does not receive stem cell therapy, the myelin sheaths that were destroyed in the relapse phase are irreversibly lost.
How long does it take for possible symptom improvement?
Typically, patients experience symptom improvement after several months of receiving therapy, with peaking results between the 3rd and 6th-month post-procedure. Some may experience feeling improvements earlier. The types of symptoms expected to improve include all signs that were triggered by multiple sclerosis-related inflammatory and immune reactions.
Is stem cell therapy superior to conventional treatment?
The answer to this question is not straightforward, as many factors fall into play. To keep it short, conventional therapy focuses on suppressing your immune system, which predisposes you to several infectious pathogens. Moreover, it cannot modulate the immune system nor regenerate the damage inflicted on the nerve fibers.
Incorporating stem cell therapy in the treatment of MS has opened a door to new opportunities to manage a condition that was initially thought incurable. It is important to remember that this is a management tool that can be done in conjunction with traditional medicine as well as healthy lifestyle choices.
by admin | May 13, 2022 | Mesenchymal Stem Cells, Stem Cell Research
Multiple system atrophy (MSA) is a rare, degenerative adult-onset neurological disorder that affects your body’s involuntary functions, including blood pressure, breathing, bladder function, and motor control. MSA also demonstrates several symptoms similar to those accompanying Parkinson’s disease, including slow movement, stiff muscles, and loss of balance[1].
Considering the rapid and fatal progression of MSA, there are not currently any long-term drug treatments known to produce therapeutic benefits against the condition. The typical neuropathological hallmarks of MSA are bone marrow destruction and cell loss in the striatonigral region of the brain that results in dopamine deficiency significant enough to result in behavioral abnormalities.
Since mesenchymal stem cells (MSCs) have demonstrated the ability to self-renew and differentiate within a wide variety of tissues, Park et al., in this study, aimed to assess whether the transplantation of human-derived MSCs could have beneficial effects in a double-toxin-induced MSA rat model. Additionally, the authors assessed the signaling-based mechanisms underlying the neuroprotective effects of MSCs.
Specifically, as part of this study, Park et al. studied the effects of MSCs in 60 rats randomly allocated to one of six groups – a control group, a double-toxin group, two groups receiving MSC intra-arterial (IA) injections, and two groups receiving MSC transplantation via intrathecal (IT) injection after double-toxin induction.
After receiving treatment each group of rats underwent a variety of tests, including the Rotarod test, gait test, and grip strength test. Additionally, the brain tissue of the rats was collected, preserved, and evaluated to assess notable differences.
At the conclusion of this study, the authors found clear evidence of the protective effects of MSCs on double-toxin-induced MSA. The study also demonstrated that transplantation of MSCs prevented neuronal cell death and improved behavioral disorders caused by double-toxin-induced MSA, specifically by reducing dopaminergic neurodegeneration and neuroinflammation.
Additionally, Park et al.’s study demonstrated a higher expression of polyamine modulating factor-binding protein 1 and a lower expression of 3-hydroxymethyl-3-methylglutaryl-COA lyase (HMGCL) after MSC transplantation.
Park et al. also point out that further investigation is required to better understand the exact mechanism of neuron-specific knockdown in vivo animal and clinical trials.
The authors of this study conclude that treating MSA with bone-marrow-derived MSCs protects against neuronal loss by reducing polyamine- and cholesterol-induced neural damage and may represent a promising new therapeutic treatment option for MSA.
Source: “Prevention of multiple system atrophy using human bone marrow ….” 11 Jan. 2020, https://stemcellres.biomedcentral.com/track/pdf/10.1186/s13287-020-01590-1.pdf.
[1] “Multiple system atrophy (MSA) – Symptoms and causes – Mayo Clinic.” 21 May. 2020, https://www.mayoclinic.org/diseases-conditions/multiple-system-atrophy/symptoms-causes/syc-20356153. Accessed 4 Apr. 2022.
by admin | May 6, 2022 | Stem Cell Therapy, Mesenchymal Stem Cells, Multiple Sclerosis, Stem Cell Research
Multiple sclerosis (MS) is a chronic inflammatory disease that attacks myelin, the protective sheath that covers nerves and causes progressive and serious communication issues between the brain, central nervous system, and the rest of the body[1].
Currently, it’s estimated that over 2.3 million people worldwide, and over one million people in the US have a diagnosis of MS[2].
While there have been significant improvements in treatments designed to stabilize, delay, and even improve symptoms of MS, new and more effective treatments are needed to improve the long-term outcome associated with the condition.
One area currently being investigated as a potential therapeutic option for treating MS is the use of regenerative medicine, also known as stem cell therapy, and specifically treatment using mesenchymal stem cells (MSCs).
In this review of evidence from preclinical and clinical studies, Gugliandolo et al. examine studies involving the use of MSCs or their derivatives in vivo models of MS and patients affected by MS. The authors also examine and discuss the feasibility of autologous MSCs therapy for MS patients.
Specifically, and when assessed in terms of effectiveness when treating MS, the therapeutic potential of MSCs was associated with their differentiation capacity and paracrine effects, their ability to differentiate toward oligodendrocytes and express oligodendrocyte progenitor cell (OPC) markers, and their capacity for homing (moving towards the damaged area following chemical gradients).
As part of this review, the authors also examined the effectiveness of various sources of MSC in MS models, these sources included bone marrow MSCs (BM-MSCs), adipose tissue-derived MSCs (AD-MSCs), periodontal ligament stem cells (PDLSCs), skin-derived MSCs (S-MSCs), Wharton’s jelly-derived MSCs (WJ-MSCs), human umbilical cord MSCs (UCMSC), human amnion mesenchymal cells (AMCs), placental derived MSCs (PMSCs), and decidua derived MSCs (DMSCs). According to the research reviewed by Gugliandolo et al., all MSCs, regardless of where they were harvested from, demonstrated beneficial effects in the therapeutic treatment of MS.
Specifically, the results demonstrated that MSCs were able to produce some form of protective effects in reducing inflammatory cell infiltration, disease score, demyelination, and blood-brain barrier disruption.
A review of 29 phase 1 or 2 clinical trials registered on clinicaltrials.gov demonstrated that MSCs, regardless of the type and method of administration, demonstrated to be safe and absent of severe adverse effects with the majority demonstrating measurable improvements when used in MS patients.
While clinical trials demonstrated the safety of administration of MSC in MS patients, the authors were particularly interested in learning if autologous MSC transplantation presented some advantages over heterologous administration.
The authors of this review found that samples obtained from healthy controls and MS patients showed similar features, indicating the possibility of autologous stem cell therapy in MS patients. However, other studies found that MSCs obtained from MS patients exhibited a different transcriptional pattern and fewer immunosuppressive functions compared to healthy donor MSCs.
Gugliandolo et al. point out that limits to these experimental studies include the use of animals of a single gender, given that sex-dependent differences exist and the use of different MS models, different number of transplanted cells, different MSCs sources, and routes of administration. These limitations make it difficult to define the optimal treatment in terms of cell type, dose, and administration conditions.
The authors conclude that clinical trials demonstrate the safety and feasibility of MSCs treatment, and also some improvements, but more data on larger cohorts are required to establish their efficacy. Considering the controversial results pertaining to the features of MSCs derived from MS patients, the authors also call for additional research in order to conclusively determine the safety and efficacy of autologous MSCs therapy in MS patients.
Source: “Mesenchymal Stem Cells in Multiple Sclerosis – NCBI.” 17 Nov. 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698327/.
[1] “Multiple sclerosis – Symptoms and causes – Mayo Clinic.” 7 Jan. 2022, https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269.
[2] “Understanding MS | National Multiple Sclerosis Society.” https://www.nationalmssociety.org/What-is-MS/MS-FAQ-s.
by Stemedix | Apr 11, 2022 | Parkinson's Disease, Mesenchymal Stem Cells, Stem Cell Therapy
Regenerative medicine, also known as stem cell therapy, is emerging as a viable treatment for Parkinson’s disease as clinical trials move through the FDA approval process. Patients in clinical trials see positive results from mesenchymal stem cell therapy for Parkinson’s Disease.
What Is Parkinson’s Disease?
Parkinson’s disease is a progressive, neurodegenerative condition. It occurs when dopamine-producing brain cells stop working or die. Dopamine’s role in the body is to send messages between nerve cells or from nerve cells to muscle cells, affecting the body’s physical and mental functions.
Symptoms of Parkinson’s start gradually, and the disease worsens over time. Early symptoms include tremors in the hands, rigidity, and slowness of movement. Patients with Parkinson’s also experience difficulty with balance, and eventually, with speech, writing, and automatic muscle movement such as blinking.
While there’s currently no cure for Parkinson’s, there are medications that patients can take to manage symptoms. Some symptoms are also relieved from surgery to regulate specific brain areas.
Patients with Parkinson’s disease experience a progressive decline in their ability to function, with treatments only offering some relief. The emergence of mesenchymal stem cell therapy as an option to reverse the damage and halt the progression of Parkinson’s disease is an exciting development.
What Are Mesenchymal Stem Cells?
Stem cells are considered to be the building blocks of cells. All specialized cells in the body come from stem cells. When stem cells divide, they either produce more stem cells, called daughter cells, or differentiate into specialized cells, such as bone, blood, or brain cells.
Mesenchymal stem cells (MSCs) are adult stem cells commonly found in bone marrow. They also exist in adipose (fat), umbilical cord tissue, amniotic fluid, and other locations. MSCs remain dormant in the bone marrow until they’re needed to facilitate healing in the body.
MSCs differentiate into:
- Bone cells
- Muscle cells
- Skin cells
- Cartilage
- Neural cells
- Corneal cells
MSCs are present throughout your life, but they age as the body ages, making them less effective and concentrated over time.
How Can Mesenchymal Stem Cells Benefit Those with Parkinson’s Disease?
In recent clinical trials using mesenchymal stem cells on Parkinson’s patients, the cells significantly improved patients’ symptoms, including facial expressions, gait, and rigidity or “freezing” episodes. Some of the patients in this study substantially reduced their dosages of medicines used to control Parkinson’s symptoms.
In a 2005 study, researchers determined that stem cells may be capable of differentiating into dopamine neurons, which are damaged or destroyed with Parkinson’s.
While the true potential of mesenchymal stem cell benefits in Parkinson’s patients is still being investigated, there is reason to believe that patients with the neurodegenerative condition could experience a significant improvement in their quality of life with stem cell therapy. If you are interested in learning more about Mesenchymal Stem Cell Therapy for Parkinson’s Disease, contact us today at Stemedix!
by admin | Apr 1, 2022 | Stem Cell Therapy, Adipose, Mesenchymal Stem Cells, Musculoskeletal, Wharton's Jelly
Articular cartilage, found on the surface of most musculoskeletal joints, distributes and transfers forces between bones and joints, provides a smooth surface for joint mobility, and plays an important role in human mobility.
However, articular cartilage is also easily susceptible to damage, but difficult to repair itself on its own (primarily due to the fact it is mostly avascular). Over time, the inability of articular cartilage to repair itself leads to progressive joint pain, disfigurement, movement disorders, and ultimately osteoarthritis.
The CDC estimates that nearly 33 million Americans are currently affected by osteoarthritis, most often in the form of pain, stiffness, decreased mobility and range of motion, and swelling in the joints[1].
Current treatment methods, including microfracture technology, autologous or allogeneic cartilage transplantation, and autologous chondrocyte implantation (ACI) have demonstrated the ability to repair and regenerate fibrous cartilage, but not articular cartilage required for smooth, fluid, natural mobility.
To address this issue, recent research has focused on the efficacy of stem cells, and specifically mesenchymal stem cells (MSCs) found in bone marrow, adipose tissue, synovial membrane, and umbilical cord Wharton’s jelly, as potential therapeutic treatments for regeneration of articular cartilage. MSCs are particularly of interest due to their demonstrated abilities of self-renewal, multi-differentiation, and immunoregulation.
While the use of MSCs has demonstrated tremendous potential in the field of regenerative therapy, one notable drawback continues to be unstable or suboptimal results resulting from the heterogeneity of various mesenchymal stem cells.
Specifically, the stability and efficacy of MSCs appear to differ based on a number of factors, including the donor, the tissue source, and their ability for proliferation, differentiation, and immunoregulation.
For example, some of the key heterological differences highlighted in this review include the efficacy of MSCs based on donor’s age (with younger donors providing higher quality MSCs), Wharton’s Jelly MSCs showing greater prospects for application in cartilage regeneration than other MSCs, and differences within specific MSC subpopulations.
The authors of this review acknowledge the potential of MSCs in repairing arterial cartilage, but also point out that there needs to be a deeper understanding of the heterogeneity of various MSCs in order to improve the efficiency of MSC-based therapies designed to repair arterial cartilage. In addition, the authors also call for greater standardization in MSC isolation and harvesting methods among laboratories in order to provide better consistency with respect to results obtained from studies using MSCs.
Source: “Heterogeneity of mesenchymal stem cells in cartilage regeneration.” 19 Mar. 2021, https://www.nature.com/articles/s41536-021-00122-6?elqTrackId=5517bd20493b470cb34fd0e8bc1f6ef9.
[1] “Osteoarthritis (OA) | Arthritis | CDC.” https://www.cdc.gov/arthritis/basics/osteoarthritis.htm.
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