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.
by admin | Jan 21, 2022 | Stem Cell Therapy, Mesenchymal Stem Cells, Stem Cell Research, Stroke
According to the CDC, stroke continues to be a major cause of serious disability for adults. It is also estimated that nearly 800,000 people in the United States have a stroke each year[1]. While 80% of those experiencing a stroke survive for at least one year following the event, more than 70% will continue to experience long-term disabilities.
Stroke is divided into three distinct phases: acute, subacute, and chronic phases. The acute phase of stroke occurs within 24 hours of the actual ischemic event. The subacute phase starts at 24 hours and lasts up to 3 months. The chronic phase of stroke, by definition, starts at 3 months.
While stroke patients tend to see some response to rehabilitation efforts occurring in the chronic phase, they tend to quickly plateau, leaving many with serious chronic neurological and functional disabilities. To date, there are no approved treatments for the chronic phase of stroke.
For the purposes of this study, Steinberg et al. report the two-year outcomes of their phase 1/2a study examining chronic stroke patients after implantation of mesenchymal stem cells (MSCs). This study specifically examined the outcomes of 18 patients who were at least 6 months post-stroke onset and had chronic motor deficits secondary to the nonhemorrhagic stroke.
At the 1-year point of this study, the authors reported the implantation of bone marrow-derived MSCs (BMD MSCs) was generally safe, well-tolerated, and associated with significant improvement in clinical outcomes.
There were no correlations between improvement in clinical outcomes and cell dose, baseline patient age, or baseline stroke severity. However, two years after implantation of MSCs, those enrolled in this study experienced significant improvement in motor impairment scales as indicated by a number of scores, including the ESS, NIHSS, F-M total, and FMMS scores.
Although all enrolled patients experienced at least one Treatment-Emergent Adverse Event (TEAE), with headache and nausea being the most common, 94.4% of the TEAEs were determined to be unrelated and no one withdrew from the study.
Interestingly, the authors reported that there also appears to be a significant correlation between the size of newly appearing transient lesions primarily in or adjacent to the premotor cortex – a finding that remained consistent at month 12 and month 24 of this study.
While Steinberg et al.’s reported findings are encouraging, the authors point out that the small scale and uncontrolled study design mean the findings should also be interpreted with caution.
Steinberg et al conclude that their findings associated with this completed, open-label, single-arm phase 1/2a study was consistent with the data at the 1-year point and indicated that treatment of chronic stroke with BMD MSCs after 2 years continued to be safe and was associated with sustained and significant improvements in clinical outcomes.
Given the findings of this study, the authors highlight the potential of MCSs, and specifically SB623 cells used in this study, as a potential treatment for patients with chronic ischemic stroke.
Source: “Two-year safety and clinical outcomes in chronic ischemic stroke ….” 23 Nov. 2018, https://pubmed.ncbi.nlm.nih.gov/30497166/.
[1] “Stroke | cdc.gov.” https://www.cdc.gov/stroke/index.htm.
by admin | Dec 31, 2021 | Stem Cell Therapy, Diabetes, Mesenchymal Stem Cells, Stem Cell Research
According to recent data from the CDC, an estimated 30 million Americans currently have type 2 diabetes mellitus (T2DM), and another 88 million are considered to be prediabetic[1].
Occurring most often as a result of being overweight and/or sedimentary and often resulting in severe kidney, heart, or vision issues, T2DM has demonstrated to be difficult to treat, often resulting in life-long insulin therapy as the primary method of treatment.
Considering the negative impacts associated with insulin treatment, and T2DM in general, Liu, et al.’s research explores the potential of specific mesenchymal stem cells (MSCs) in the treatment of the condition.
Recently, stem cell therapy has been shown to be beneficial in improving glycemic control and beta function. Building off of these findings, Liu, et. al designed this study to specifically examine the efficacy and safety of Wharton’s Jelly mesenchymal stem cells transplantation (WJ-MSC) as a therapeutic option for those with T2DM.
The authors’ single-center phase I/II study involved observing 22 patients with T2DM for 12 months after receiving two injections of WJ-MSC (one intravenously and one intrapancreatic endovascularly). Over the course of the 12-month observation period, the participants were monitored with primary endpoints observed including changes in the levels of glycated hemoglobin and C-peptide and secondary endpoints including insulin dosage, fasting blood glucose, post-meal blood glucose, inflammatory markers, and T lymphocyte counts.
At the conclusion of this study, Liu et al. found that both glycated hemoglobin and fasting glucose levels demonstrated a progressive decline after WJ-MSC transplantation and over the course of the 12-month follow-up period, the suggested potential of long-lasting effects of the WJ-MSC treatment. Researchers also observed a general improvement in fasting C-peptide levels. Secondary endpoint observations over the course of the 12-month follow-up included improved beta-cell function and reduced markers of systemic inflammation and T lymphocyte counts.
While there were no significant adverse observed effects associated with either of the WJ-MSC injections, the authors did note isolated and separate incidences of mild fever, nausea, and headache in a very small number of participants – all of which spontaneously resolved within a week of onset. The authors also noted a temporary decrease in levels of C-peptide and beta-cell function one month after treatment, possibly related to the intrapancreatic endovascular injection. As a result of these observations, the authors call for further investigation of the safety of intrapancreatic endovascular delivery of WJ-MSC.
As a result of this research, Liu et al. concluded that their findings suggest the possible therapeutic potential of WJ-MSC transplantation for treatment of T2DM and specifically with improved beta-cell function, systemic inflammation, and immunological regulation. The authors also call for further large-scale placebo-controlled clinical studies to fully understand the safety and efficacy of WJ-MSCs in the treatment of T2DM. Source: “PMC – NCBI.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055092/
[1] “Type 2 Diabetes | CDC.” https://www.cdc.gov/diabetes/basics/type2.html. Accessed 22 Jan. 2022.
by admin | Dec 10, 2021 | Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Articular cartilage is the smooth, white cartilage that covers the ends of the bone in diarthrodial joints. Essential for fluid and pain-free movement, articular cartilage protects the bones by reducing friction and absorbing shock.
However, articular cartilage is also subject to damage and injury as a result of normal wear and tear or as a result of a number of conditions, including osteoarthritis (OA), osteonecrosis, and osteochondritis. Articular cartilage has been found to have a weak capacity for self-repair, mostly a result of having no blood, lymphatic, or nerve supply.
Until recently, the primary option for treatment of joint cartilage defects, including damage to articular cartilage, involved a series of invasive marrow simulating techniques, including microfracture, Pridie drilling, and abrasion arthroplasty which generally produced inferior results.
The search for alternative and more effective treatment options for damaged joint cartilage has recently led scientists to identify mesenchymal stem cells (MSCs) as an appropriate cellular material for repair of joint cartilage, and specifically for articular cartilage.
As part of this review, authors Eslaminejad and Poor examine and identify the past attempts to use MSCs as a way to cure articular cartilage defects occurring as a result of OA, rheumatoid arthritis (RA), and trauma. In addition, the authors further discuss the specific characteristics that led scientists to conclude MSCs to be an appropriate cell candidate for regenerating articular cartilage, including their inherent chondrogenic property, ease of availability, cell homing potential, and immunomodulatory function.
MSCs demonstrate the ability for long-term self-renewal and the capacity to differentiate along multiple cell lineages – including cartilage cells. While bone marrow has been found to possess low numbers of MSCs, the cells have been easily multiplied through standard lab-based culture techniques. In addition, MSCs are considered readily available cells for application in regenerative medicine, thanks in large part to their availability from a number of sources in the body, including adipose tissue, synovial membrane, and skeletal muscle.
Among the most compelling reasons for MSCs being considered appropriate for the repair of articular cartilage is their homing potential. Specifically, the homing potential of MSCs is thought to help repair damaged cartilage by differentiating into tissue cells to restore function and by secreting a number of bioactive factors to create a repair environment with anti-apoptotic effects, immunoregulatory function, and stimulation of endothelial progenitor cell proliferation.
While using MSCs to repair damaged articular cartilage appears to have tremendous potential, the treatment is not without potential drawbacks or concerns. Among the most pressing of these concerns is that MSCs-regenerated cartilage is potentially too thin to resemble mature cartilage and hypertrophy resulting from MSC-regeneration could lead to ossification of cartilage tissue.
As such, there have been several recent attempts to evaluate the potential of using MSCs to regenerate articular cartilage in both animals and humans, with all demonstrating some degree of enhanced healing and repair by using MSCs as treatment.
The authors conclude that while using MSCs in the repair of damaged articular cartilage appears to have tremendous potential for long-term clinical success, they also call for further research into a number of areas, including improving the quality of repair tissue formed following MSC transplantation, enriching the cell population for chondrogenic cells, and further study into developing a safe and highly efficient gene delivery system for MSCs used in the regeneration and repair of articular cartilage.
Source: “Mesenchymal stem cells as a potent cell source for articular … – NCBI.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131275/.
by admin | Nov 26, 2021 | Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
When it comes to their potential for biomedical applications, mesenchymal stem cells (MSCs) continue to garner support and attention from the global scientific community. Isolated from a variety of sources, including bone marrow, adipose tissue, and umbilical cord tissue, MSCs demonstrate multipotent differentiation in vitro. In other words, they are tissues that are able to develop into more than one type of cell.
Considering MSCs ability to expand into osteogenic, chondrogenic, adipogenic, and myogenic cells for the purposes of repair and recovery, they continue to attract attention for treating a wide variety of conditions, including inflammatory lung and musculoskeletal disorders, multiple sclerosis (MS), and Crohn’s disease (CD).
As part of this review, Markov et al. provide a brief overview of MSC sources, migration process, and unique immunomodulatory attribute’s mechanisms while also focusing on the current findings pertaining to the immunoregulatory plasticity of MSCs and how that contributes to the regulation of immune response to elicit the desired therapeutic outcomes in patients suffering from immune-mediated/immune-dysregulating diseases.
Interestingly, the ability of MSCs to exhibit anti-inflammatory and regenerative properties has proven beneficial in clinical trials exploring therapeutic treatments of a number of immune-mediated disorders, including osteoarthritis, rheumatoid arthritis, and MS. Specifically, the findings of these clinical trials provide evidence that MSCs replace injured tissues while also serving as a source of growth factors and regenerative molecules. These findings also demonstrate that specific differential molecular mechanisms, when correctly identified, appear to be able to adjust the potential of MSCs in the regeneration of damaged tissue.
This review also explores the immunomodulatory properties of MSCs. Specifically, MSCs have been found to modify immunological reactions in several ways, including T cell suppression and induction of macrophages shift from M1 to M2, making MSCs an emerging therapeutic treatment option to a number of immune-mediated disorders including systemic lupus erythematosus (SLE), MS, OA, RA, and CD.
Despite the observed benefits of MSCs in treating these immune-mediated disorders, the authors call for additional large-scale studies over prolonged periods of evaluation before fully utilizing MSCs in clinical applications.
Given their ability to differentiate into a wide variety of cells, their immunomodulatory competence, and lower ethical concerns, Markov et al. conclude that MSCs have good reason to be considered a viable therapeutic option for the treatment of a wide range of immune-mediated disorders.
While animal studies continue to provide evidence of the safety, feasibility, and efficacy of administration of MSCs in immunological disorder, the authors point out that potential of MSCs have not yet been fully realized through human clinical outcomes. Considering this, the authors call for further investigation and study to better understand how recruiting MSCs can improve migration and homing following transplantation.
Finally, the authors point out that enriching MSC culture, choosing appropriate induction factors, and exploring new ways to promote MSCs homing post-transplantation when accompanied by further exploration of optimal MSC dose and route will further improve therapeutic outcomes in patients with immune-mediated diseases.
Source: (2021, March 18). Mesenchymal stem/stromal cells as a valuable source for the … – NCBI. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971361/
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