With more than 17,000 people in the US sustaining a spinal cord injury (SCI) each year and an estimated combined cost to healthcare and the workforce exceeding $40 billion, the condition has significant personal and socioeconomic implications. In addition, SCIs have limited pharmacological treatment options to support the regeneration of nerve damage.
Considering the limited treatment options for this condition, the field of regenerative medicine, and specifically the use of stem cells, has recently drawn interest as a potential therapeutic treatment option for paralysis resulting from SCIs.
In this report, Bydon et al. summarize findings of the ongoing multidisciplinary phase 1 clinical trial exploring the safety and efficacy of intrathecal autologous adipose tissue-derived (AD) mesenchymal stem cells (MSCs) in patients with blunt, traumatic SCI.
Specifically, as part of this report, the authors describe the outcome of the first patient with C3-4 SCI treated with AD-MSCs. At the time of SCI, neurologic examination revealed complete loss of motor and sensory function below the level of injury; an injury diagnosed as an American Spinal Injury Association (ASIA) grade A SCI.
After undergoing initial treatment, including C2-6 posterior cervical decompression and fusion, improvement in motor and sensory function was demonstrable. However, neurological gains plateaued 6 months after sustaining injury.
Upon enrollment into the CELLTOP clinical trial 9 months after injury, the patient’s neurologic status was found to be ASIA grade C and imaging revealed bilateral myelomalacia at the C3 level and at the C2-6 decompression and fusion. Additionally, an open biopsy of adipose tissue found in the abdominal wall was performed 8 weeks prior to receiving an initial intrathecal injection.
After receiving an intrathecal injection of 100 million autologous AD-MSCs 11 months after injury, the patient was observed for clinical signs of efficacy at 3, 6, 12, and 18 months following injection.
Bydon et al. observed progressive improvement in upper extremity motor scores and considerable improvement in lower extremity scores at 18 months following injection. The patient also demonstrated consistent improvement in ASIA sensory score, including improvements in pinprick and light touch scores at follow-up after 18 months. The authors reported patient improvements in Capabilities of Upper Extremity score, quality of life (as measured by Global Health Score), and in physical and occupational therapy measures. Other than a moderate headache on day 2, no other safety issues or adverse events were reported.
While further clinical trial is required, the authors conclude that intrathecal AD-MSC administration may be a relatively noninvasive and safe therapeutic option for patients with SCI to improve their neurologic status after reaching a ceiling effect in terms of spontaneous recovery.
No one wants to grow old. That is apparent from the huge amounts of money people spend on anti-aging products and services each year. These products and services include everything from lotions to more invasive options like plastic surgery.
However, healthier aging is possible without relying on invasive procedures. Stem cell rejuvenation, for example, offers promising results for people searching for ways of going through a healthier aging process.
Intrinsic vs. Extrinsic Aging: What to Know
Intrinsic aging refers to the various traits you inherited, including collagen and elastin production levels, hormonal balance, and more. The thinning lips or particular types of wrinkles you see on your parents, for example, are intrinsic aging traits, and you will likely deal with them as you age, too.
Intrinsic aging doesn’t just refer to visible signs of aging. It also includes the damage that occurs to organs and other body tissues as you get older. How fast an organ deteriorates and how fast tissues regenerate to keep up with the damage all depends on intrinsic aging.
Extrinsic aging refers to the things that you can control about aging. It includes lifestyle choices like smoking, not eating correctly, and so much more.
Both intrinsic and extrinsic factors in aging begin to accumulate, sending messages of aging to the core of stem cells. Thus, everything associated with aging can be seen through the lens of stem cells.
Understanding Stem Cell Rejuvenation
Introducing youthful stem cells into the body can make it easier to rejuvenate existing cells, helping the body age in a healthier way and even offering the chance to reverse some of the effects of aging.
As you age, your cells are not as efficient at replicating as they were when you were younger. This leads to cells getting damaged and dying off. Inefficiency in cell replication leads to aging bodies.
Stem cells are the cells that create specialized cells. They are your body’s building blocks. To combat the natural aging process, stem cells can help regenerate damaged tissue. This is because they can be made into various cell types.
Stem cells can also stimulate the production of growth factors and other molecules that trigger healing mechanisms, helping maintain healthy tissues. Chronic, low-grade inflammation is associated with aging, and stem cells help to reduce inflammation.
They do this by impacting the processes of white blood cells. Macrophages are white blood cells that are integral to the immune system. M1 macrophages can create inflammation, while M2 macrophages reduce it.
Stem cells help transform M1 macrophages into M2 macrophages. This stimulates the process of reducing inflammation.
Another way stem cells help battle against the aging process is by modulating the immune system. They have the potential to maintain a healthy immune system and delay the type of immune dysfunction that comes with age.
Oxidative stress also plays a role in aging. Free radicals damage cells, leading to many of the issues the aging process causes. Stem cells help combat the effects of oxidative stress.
Stem cells also have the potential to affect visible signs of aging. They can increase collagen production, which is vital for maintaining skin flexibility and firmness. As part of the aging process, your collagen production decreases, leading to the formation of fine lines and wrinkles.
The Process of Stem Cell Rejuvenation
Stem cell rejuvenation begins with choosing the right type of stem cells. The main stem cell type used is mesenchymal stem cells.
Mesenchymal stem cells (MSCs) are a type of multipotent stem cell that can differentiate into a variety of cell types. They are typically found in the stromal or connective tissue of various organs and tissues in the body.
MSCs were first identified in the bone marrow, but they can also be isolated from other tissues such as adipose (fat) tissue, and umbilical cord tissue.
MSCs possess immunomodulatory properties, meaning they can regulate the immune system. They can influence the activity of immune cells, such as T cells and macrophages, and have anti-inflammatory effects. This makes them potentially useful for treating conditions with immune system dysregulation.
MSCs exhibit low immunogenicity, meaning they are less likely to provoke an immune response when transplanted into a recipient. This characteristic makes them potentially suitable for allogeneic (from a donor) transplantation.
MSCs have been studied for their potential therapeutic applications in regenerative medicine, tissue engineering, and treatment of various diseases, such as autoimmune disorders, cardiovascular diseases, and musculoskeletal conditions.
If from a patient’s own tissues, the healthcare provider extracts the stem cells and prepares them for injection. They then inject the stem cells into the treatment area to provide relief from inflammation while encouraging your body to start regenerating tissues at the same time.
Because stem cells have the ability to endlessly duplicate themselves, the benefits of stem cell therapy for rejuvenation purposes can only improve over time.
Benefits of Stem Cell Rejuvenation
Stem cell rejuvenation procedures are minimally invasive. They require an extraction of stem cells and then an injection or the introduction of an IV. Other procedures that target aging can be significantly more invasive, leading to long recovery times.
The results continue to improve over time. This is because stem cells will go on to multiply where they were injected, potentially leading to more powerful results.
Stem cell rejuvenation can target the aging process at the cellular level, helping reduce inflammation and prevent oxidative stress. Stem cells may lead to an increase in collagen production as well, which helps combat fine lines and wrinkles.
Choosing Regenerative Medicine
Anti-aging solutions don’t have to involve invasive procedures or the reliance on options that take a very long time to work. Regenerative medicine treatments like stem cell therapy offer the chance to tackle the causes of aging at the cellular level.
Stem cells can offer anti-inflammatory results while also targeting free radicals and helping repair damaged tissues as well as damaged stem cells. By turning to regenerative medicine options, you have the chance to find rejuvenation solutions that can work.
Mesenchymal stem cells (MSCs) isolated from a wide variety of tissues and organs have demonstrated immunomodulatory, anti-inflammatory, and regenerative properties that contribute to a host of regenerative and immunomodulatory activities, including tissue homeostasis and tissue repair. The most frequently studied and reported sources of MSCs are those collected from bone marrow and adipose tissue.
In this review, Krawczenkjo and Klimczak focus on MSCs derived from adipose tissue (AT-MSCs) and their secretome in regeneration processes.
Adipose tissue is the most commonly used source of MSCs, primarily because it is easily accessible and is often a byproduct of cosmetic and medical procedures. Like most MSCs, AT-MSCs are able to differentiate into adipocytes, chondrocytes, and osteoblasts; they are also able to differentiate into neural cells, skeletal myocytes, cardiomyocytes, smooth muscle cells, hepatocytes, endocrine cells, and endothelial cells.
In addition, AT-MSCs secrete a broad spectrum of biologically active factors that serve as essential components involved in the therapeutic effects of MSCs, including the ability to stimulate cell proliferation, new blood vessel formation, and immunomodulatory properties; these factors include cytokines, lipid mediators, hormones, exosomes, microvesicles, and miRNA.
Preclinical and clinical studies on AT-MSCs in tissue regeneration were demonstrated to contribute to wound healing, muscle damage, nerve regeneration, bone regeneration, and lung tissue regeneration.
Evaluating these studies, Krawczenko and Aleksandra Klimczak conclude that AT-MSCs and their secretome are promising and powerful therapeutic tools in regenerative medicine, primarily due to their unique properties in supporting angiogenesis.
The results obtained by the preclinical and clinical studies evaluated for this review suggest that the ability of AT-MSCs and their derivatives, including EVs and CM, to deliver a wide range of bioactive molecules could be considered as factors supporting enhanced tissue repair and regeneration.
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.
Osteoarthritis is the most common form of arthritis, affecting more than 900 million people around the world. Developing when the cartilage that protects your bones wears down, osteoarthritis (OA) most commonly affects the joints of the hand, hips, spine, and knees[1].
While current treatment for OA and related joint damage is focused primarily on managing pain and minimizing further damage, function, and quality of life issues, no preventative therapeutic treatment currently exists for preventing or rehabilitating the condition.
Recently, stem cell therapy has been found to be an efficient therapeutic approach for treating degenerative joint conditions, including OA. Specifically, mesenchymal stem cells (MSCs), from adipose cells have been demonstrated to be the most promising type of stem cell for treating osteoarthritis.
In this study, Bui et al. studied the outcomes of applying MSCs harvested from adipose tissue in an effort to evaluate the therapeutic potential when transplanted in patients with grade II and III osteoarthritis.
Previous studies have demonstrated that PRP treatment of ADSCs promotes differentiation and proliferation into chondrogenic cells which resulted in improved healing of articular cartilage when ADSCs were pretreated with PRP. An additional study demonstrated the effects of PRP on the non-expanded stromal vascular fraction (SVF) in cartilage injury observed in an animal model, demonstrating significant regeneration of cartilage.
The aim of this clinical trial was to evaluate the efficiency and related side effects of non-expanded SVF when combined with PRP in treating OA grade II or III.
At the conclusion of Bui et al.’s study, patients demonstrated significant improvements in key measures, including improved joint function, decreased pain score, and improved gradual and consistent improvement observed in pre and post observations as measured by the Lysholm score.
As further evidence of the success associated with a therapeutic treatment combination of ADSC and PRP, post-treatment MRIs demonstrated cartilage regeneration and thicker layers of cartilage at the injured site after 6 months of treatment. In addition, all participating patients reported reduced pain levels after 3 months and 71% of patients demonstrated the ability to climb and descend stairs after 3 months. None of the patients participating in this study demonstrated infection, tumor formation, or any other side effect or complication as a result of this procedure.
As a result of their findings in this study, Bui et al. conclude that this therapeutic treatment method was successful in reducing pain, regenerating cartilage, and improving the quality of life for patients who participated. However, considering the small size of this study, the authors call for additional and larger-scale studies to confirm the potential for this promising, minimally invasive stem cell therapy for patients with osteoporosis.
The immunosuppressive ability of mesenchymal stem cells (MSCs) coupled with their potential to serve important therapeutic roles in a wide range of immune disorders have resulted in a significant increase in the number of clinical studies examining the role of cellular therapy in a wide range of applications.
Of particular interest is MSCs’ ability to migrate towards inflamed environments, produce anti-inflammatory cytokines, and their ability to conceal themselves from the natural immune system.
As part of this review, Mishra et al. address the immunomodulatory properties and immunosuppressive actions of MSCs. The authors also summarize various responses of MSCs in treating a number of immune disorders, including inflammatory diseases, metabolic disorders, and diabetes.
Immunomodulation has been identified as one of the primary functions of MSCs, autocrine and paracrine activities, and evasion of innate immunity. When it comes to immunomodulation, and depending on their specific environment, MSCs have been demonstrated to be either pro or anti-inflammatory.
In certain situations, and when exposed to low levels of pro-inflammatory cytokines, MSCs have been shown to produce an enhanced immune response with neutrophils moving to the site of inflammation and acting mainly by phagocytosis. On the other hand, when part of the anti-inflammatory conditions, and especially in wounds, infections, and organ transplants, MSCs have successfully demonstrated the ability to suppress the immune response.
Research has demonstrated MSCs to have beneficial effects on many different disease models, including myocardial infarction, hepatic fibrosis, and cancer.
Interestingly, the authors of this review point out that, although adipose tissue is considered to be the preferred source of adipose-derived mesenchymal stem cells – specifically for its potential related to healing, tissue engineering, and hepatocellular carcinoma – the health of the adipose tissue appears to matter. Specifically, it appears that adipose tissue gathered from obese patients demonstrates the potential to be dysfunctional. Adipose tissue dysfunction resulting from overnutrition demonstrates an increase in serious LDL and VLDL which ultimately is thought to contribute to impaired multipotency of MSCs.
While Mishra et al. conclude that MSCs possess the potential for significant therapeutic benefits, they also call for future research with standardized and validated isolation and culture protocols with lineage differentiation and stimulation method to ease the animal and clinical studies. They also point out that in order to further understand the therapeutic potential of MSCS, additional study of cell modification, injection frequency, and dosages is required.
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