Worldwide, an estimated 10 million people suffer some form of traumatic brain injury (TBI) severe enough to result in either death or hospitalization each year. Nearly 20% of these TBIs occur in the United States and over 50,000 of those affected die as a result of their injury.
Characterized by a wide range of physical, psychological, and emotional impairments that range from mild memory and mood disorders to severe loss of body control and coma, TBIs are most often caused by a serious blow to the head or neck area[1].
Research has confirmed that the initial trauma resulting from the TBI is not the only factor causing damage to the brain. After sustaining an initial injury, the brain initiates a series of complex biochemical responses that significantly influence the overall severity of the damage caused as a result of the injury.
TBIs come with a tremendous cost, with direct and indirect costs estimated at over $60 billion per year in the United States alone. Additionally, there has been limited success in identifying therapeutic or pharmacological treatments that improve the long-term prognosis of moderate to severe TBI.
Considering the recent success of regenerative therapies in the treatment of a number of serious health conditions, researchers are optimistically exploring the potential benefits of using stem cells, specifically mesenchymal stem cells (MSCs), as a possible way to restore functionality to damaged neurons in and around the brain.
In this publication, Hasan et al. review numerous studies investigating the effects of the infusion of MSCs into animal models of TBIs and summarize the advances in the application of MSCs in the treatment of TBI. MSCs are multipotent stromal cells and are available for extraction from all tissue in the body.
Adding to the potential benefits offered by MSCs, they have been found to differentiate into a wide range of cell lines (not just mesenchymal cells) making them an easily accessible and potentially highly effective option for use in the regenerative treatment of TBIs.
In addition, MSCs have been observed selectively migrating and settling within injured tissue, which adds additional benefit for treatment within previously undeliverable or difficult-to-deliver sites such as the brain and the heart.
The growing evidence supporting the efficiency of using MSCs to alleviate the long-term and debilitating effects of TBI has been further bolstered by recent research highlighting the potential for the genetic modification of MSCs as a way to enhance the survival of stem and neuronal cells. Coupled with additional findings in human trials demonstrating that oxidative stress production can be manipulated by MSCs and therefore contribute to the brain’s recovery after injury, researchers are increasingly optimistic that MSC-based approaches offer significant benefits for the treatment of TBIs.
Hasan et al. also point out several concerns and potential challenges of using MSCs in the treatment of TBIs that need to be further explored and better understood before regular use in clinical settings can be approved. Among these concerns, the authors point out, is that a better understanding of the mechanisms of MSC homing in TBI-affected regions of the brain is important in order to employ them efficiently in clinical settings. Another area requiring further research is a better understanding of the respective roles of paracrine effects, transdifferentiated cells, and other factors related to tissue repair. The authors also identify a recent concern over the potential role of MSCs in the development of cancer and autoimmune diseases as a cause for further study of this potential treatment.
Despite the areas identified as in need of further research, the authors conclude that MSCs continues to demonstrate great potential in the field of regenerative medicine and specifically with respect to their use in the treatment of TBI.
Developing weak and brittle bones from osteoporosis can lead to mild bone stress — like that from bending over — causing a fracture. Most bone fractures from osteoporosis occur in the wrist, hip, or spine. While there is no cure for osteoporosis, there are treatments and medications that can help strengthen and protect your bones. Here we will discuss the benefits of Regenerative Medicine for Osteoporosis.
What Causes Osteoporosis?
Bones are living tissue. Your body constantly breaks down old bone cells and replaces them with new cells. Young bodies form new bone faster than old bone breaks down, increasing bone mass. That process slows in your early 20s, and bone mass typically peaks by the age of 30.
After your bone mass peaks, the formation process slows, and you begin losing bone faster than you create it, causing a loss of bone mass.
Many factors contribute to developing osteoporosis. Your bone mass development is partially inherited, but it’s also affected by hormone levels, diet, exercise, medical conditions, and lifestyle choices.
How Does Regenerative Medicine Work?
Regenerative medicine, also known as stem cell therapy, involves stem cells that are often called the building blocks of all cells. They contain unique healing capabilities, as they’re the only cells in the body that can divide to create two more stem cells or differentiate to form two new specialized cells.
Stem cells lie dormant in tissue like bone marrow or adipose tissue (fat) until they’re needed to restore damaged or dead cells. Stem cell therapy extracts those dormant stem cells, then injects them into damaged areas to foster healing.
How Can Stem Cells Treat Osteoporosis?
From the beginning, researchers sought out mesenchymal stem cells (MSCs) to help manage osteoporosis. They believed that MSCs would increase bone mass by producing new bone cells faster than they age, similar to the process that happens in your youth.
They were pleased to find that MSCs have even more capabilities in treating osteoporosis than expected, as they secrete bioactive molecules and growth factors fostering bone tissue repair and remodeling.
Combining MSCs’ growth factor secretion and differentiation capabilities allows them to repair and restore bone cells efficiently. As a result, stem cell therapy has the potential to help manage the effects of osteoporosis and potentially restore bone strength and mass.
While research continues around specific protocols for using stem cells to manage osteoporosis, early studies show promise for this groundbreaking therapy. To learn more about regenerative Medicine for Osteoporosis contact a care coordinator today at Stemedix!
Mesenchymal stem cells (MSCs) are multipotent fibroblast-like cells found throughout the body and have been found to have self-renewing and multilinear therapeutic potential by providing new cells for tissue repair by replacing damaged cells.
Thought to stimulate repair and control the immune response through an expression of growth factors and other cytokines, MSCs are at low risk of rejection and repair tissue damage through immunomodulation, not by their ability to differentiate.
While MSCs can be isolated from a number of tissue sources, including bone marrow, peripheral blood, adipose (fat) tissue, umbilical cord blood, and umbilical cord tissue (Wharton’s jelly). MSCs derived from the human umbilical cords (UCMSCs) have been found to have significant advantages over MSCs isolated from other sources. These advantages include higher proliferation and self-renewal capacity and multilineage differentiation capability.
Unlike many sources of MSCs, the umbilical cord is considered medical waste, making the collection of UCMSCs noninvasive and eliminating ethical concerns associated with the collection of MSCs from other sources. These UCMSCs have been developed as effective “off-the-shelf” cell therapy for a number of conditions, including autoimmune diseases, and as a treatment for a number of emergency medical conditions.
This Phase 1 clinical study, designed and conducted by Chin et al., intended to determine the safety and efficacy of intravenous allogeneic infusion of UCMSCs in healthy volunteers and to determine the effective dose at which an immunomodulatory effect is observed. The findings of this study are intended to serve as a guideline and benchmark for future CVL-100 clinical research.
Analyzing the results of this clinical study, the authors report that there was no observed complication resulting from the infusion and no significant adverse event in either dosage group in the 6 months of follow-up. These findings led Chin et al. to conclude that UCMSCs infusion was safe among healthy subjects, results that were consistent with other UCMSC treatment-based studies.
The authors also reported that UCMSCs infusion posed no significant adverse effects in patients with type 2 diabetes. Despite the relatively small sample group of this study (11 subjects), the authors reported demonstrating an initial transient proinflammatory effect followed by a significant and prolonged anti-inflammatory effect.
In addition, Chin et al. report found that high-dose (HD) CLV-1000 infusion provided a significant increase in both hemoglobin level and MCV level that falls within the normal range. Biomarker assessment results also indicated that the HD group demonstrated a significant steady increase of cytokine IL-1RA from baseline up until 6 months of posttreatment. This finding is especially important as IL-1RA is a naturally occurring antagonist to the proinflammatory cytokine 1L-1.
The authors conclude that this study clearly demonstrates a difference in immunomodulatory effect between the high-dose and low-dose treatment groups, with the HD group demonstrating a significantly greater reduction of proinflammatory cytokine TNF-α and an increased level of specific anti-inflammatory cytokines within 6 months and in relation to those in the low dose group. Considering this, Chin et al. conclude that a CLV-100 dosage of two million MSCs per kilogram of body weight represents the optimal dose level for overcoming inflammatory conditions by displaying the best improvement in all parameters tested, absence of side effects, and SAEs.
The data collected in this study also suggests that this is the first study to report a significant reduction of globulin observed over the course of the study. This is important because globulin serves an important role in immunity. Additionally, increases in serum globulins are associated with several immune-mediated diseases, including rheumatoid arthritis, chronic liver disease, diabetes mellitus, and cancer.
Considering these findings, the authors of this study conclude that high doses of allogeneic MSCs could help exert beneficial effects of repair and healing.
Osteoarthritis (OA) is the most common form of arthritis and affects an estimated 25% of adults in the United States. Characterized by pain, stiffness, and inflammation in the joints of the body, OA is most frequently observed in the knees, hands, hips, and spine.
OA is one of the leading causes of disability with an annual cost of medical care and lost earnings exceeding $300 billion. With over 250 million people affected by OA worldwide, the combination of aging, obesity, and increased incidents of oxidative stress is causing the condition to become increasingly prevalent.
To date, treatment and medical interventions – including exercise, physical therapy, lifestyle modifications, and prescription and over-the-counter medications – have been successful in managing symptoms, reducing pain, and maintaining joint mobility, but have not been able to promote the regeneration of degenerated tissue.
Stem cells, and specifically mesenchymal stem cells (MSCs), have been identified as a potential therapy option for OA. In this review, Zhu et al. summarize the pathogenesis and treatment of OA and review the current status of MSCs as a potential treatment option for the condition.
In reviewing the pathogenesis of OA, the authors highlighted the fact that OA is a dynamic and progressive degenerative disease that is primarily caused by the imbalance between restoration and destruction of the joints; the disease is also significantly influenced by environmental, inflammatory, and metabolic aspects.
The authors highlight that the primary goals of current OA treatment methods are to reduce pain, slow progression, and preserve and improve joint mobility and function.
As researchers continue to search for therapies that encourage the regeneration of damaged articular cartilage and the alleviation of inflammation, they’ve turned their attention to a number of stem cell-based therapies, such as autologous chondrocyte implantation (ACI). While ACI has received FDA approval, unexpected dedifferentiation, and joint invasiveness during harvest limit the availability and usefulness of this application.
Fortunately, MSCs have not been found to demonstrate limitations similar to those observed in ACI and are considered novel therapeutic agents for the treatment of OA. Prized primarily for their ability to stimulate cartilage formation and for their vascularization, anti-inflammation, and immunoregulation, MSCs are sourced from different types of stem cells, including bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and umbilical cord (UC-MSCs). Zhu et al. summarize the characteristics, advantages, and disadvantages of each of these MSC sources in this review.
The authors point out that several clinical trials have proven both the safety and potential efficacy of BM-MSCs, AD-MSCs, and UC-MSCs in the treatment of OA. However, the authors also point out that several of these trials were conducted with limited samples, without rigorous controls, and with relatively short-term follow-up. Considering this, Zhu et al. call for additional clinical trials using larger samples, more rigorous controls, and additional long-term follow-up. In addition, the authors also call for additional considerations to further enhance the efficacy in clinical trials, including cell density, time and location for MSC transplantation, and pretreatment of MSCs by inflammatory cytokines.
The authors conclude that while stem cell-based therapy, and specifically MSCs, demonstrate great potential for the regeneration of new cartilage and strong immunoregulatory capacity, the identified limitations and risks of MSC-based therapy should be realized and treated carefully.
Despite the identified risks and limitations, MSC-based therapy for the treatment of OA might achieve better efficacy in regenerative medicine, especially when administered in combination with other treatment options.
Mesenchymal stem cells (MSCs) have been widely used in a number of applications designed to aid in the regeneration and healing of human tissue. Prized for their multipotent capacity to differentiate into a variety of other specific cell types, MSCs have consistently demonstrated the ability to seek out damaged tissue while also reducing inflammation and promoting healing.
Recently, the discovery of a specific type of MSC known as circulating mesenchymal stem cells has demonstrated increased potential for the use of MSCs in the regeneration, repair, and engineering of tissue throughout the body.
Circulating MSCs demonstrate characteristics similar to MSCs that are derived from bone marrow and are typically found in very low concentrations in healthy individuals. While these specific MSCs have demonstrated the ability to migrate to the site of damaged or injured tissue like other MSCs, what makes circulating MSCs so interesting to researchers is their distinct genetic profile – especially when compared to bone marrow-derived stem cells (BM-MSCs).
Xu and Li’s review provides a summary of the basic knowledge of circulating MSCs, their potential clinical applications, and the issues of using allogeneic MSCs for clinical therapy.
While these circulating MSCs, also known as peripheral blood-derived MSCs (PB-MSCs), have great potential in the field of tissue engineering and regeneration, they are found in very low quantities within the human body. As a point of reference, Xu and Li point out that the frequency of BM-MSCs in humans under normal conditions is very low and ranges from 1 in 104 to 1 in 105. Compared to BM-MSCs, the concentration of circulating MSCs is even lower, typically around 1 in 108.
Despite their low numbers, researchers have successfully identified and collected PB-MSCs in both animal and human models. In both scenarios, PB-MSCs demonstrated characteristics of cell proliferation and multi-differentiation potential that are similar to those observed in BM-MSCs. In addition, and adding to their potential, PB-MSCs are plastic-adherent, have multi-differentiation potential, and demonstrate the ability to differentiate into a variety of cells.
Adding to the benefits described above, and unlike stem cells harvested from embryonic sources, PB-MSCs are not attached to ethical concerns. In addition, numerous research studies have demonstrated the use of MSCs in a variety of applications, including cardiovascular, bone, and cartilage repair have resulted in general significant improvements in tissue healing and regeneration.
To date, studies specific to circulating MSCs are rare. However, Xu and Li highlight that circulating MSCs, while originally found in the bone marrow and other sources throughout the body, are a special subset of MSCs found in circulation. While additional study is required, early research seems to indicate that the release of these circulating MSCs is tightly controlled by a variety of systematic and local factors, including inflammatory cytokines, hormones, and a variety of growth factors.
There is increasing evidence that indicates MSCs are immunosuppressive cells and that allogeneic MSCs may be used with similar therapeutic efficacy to autologous MSCs. Considering this, Xu and Li conclude that allogeneic transplantation seems to be more promising and a way to ensure that patients can receive treatment at the best time and without significant fear of rejection.
As research continues to explore the potential benefits and drawbacks of circulation MSCs, the authors point out that a lack of standard procedures for therapeutic MSC administration remains a critical issue for the clinical application of MSCs. These critical issues need to be addressed through carefully designed animal and clinical trials before clinical applications of MSCs can be used in patients with certain diseases.
This website and its contents are not intended to treat, cure, diagnose, or prevent any disease. Stemedix, Inc. shall not be held liable for the medical claims made by patient testimonials or videos. They are not to be viewed as a guarantee for each individual. The efficacy for some products presented have not been confirmed by the Food and Drug Administration (FDA).
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