Reproductive disorders, including intrauterine adhesion (IUA), premature ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS), are great threats to female reproduction. Recently, mesenchymal stem cells derived–extracellular vesicles (MSC-EVs) have presented their potentials to cure these diseases, not only for the propensity ability they stemmed from the parent cells, but also for the higher biology stability and lower immunogenicity, compared to MSCs. EVs are lipid bilayer complexes, functional as mediators by transferring multiple molecules to recipient cells, such as proteins, microRNAs, lipids, and cytokines. EVs appeared to have a therapeutic effect on the female reproductive disorder, such as repairing injured endometrium, suppressing fibrosis of endometrium, regulating immunity and anti-inflammatory, and repressing apoptosis of granulosa cells (GCs) in ovaries. Although the underlying mechanisms of MSC-EVs have reached a consensus, several theories have been proposed, including promoting angiogenesis, regulating immunity, and reducing oxidate stress levels. In the current study, we summarized the current knowledge of functions of MSC-EVs on IUA, POI, and PCOS. Given the great potentials of MSC-EVs on reproductive health, the critical issues discussed will guide new insights in this rapidly expanding field.
Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open Label Trial
Despite advances in early diagnosis and behavioral therapies, more effective treatments for children with autism spectrum disorder (ASD) are needed. We hypothesized that umbilical cord blood derived cell therapies may have potential in alleviating ASD symptoms by modulating inflammatory processes in the brain.
Accordingly, we conducted a phase I, open-label trial to assess the safety and feasibility of a single intravenous infusion of autologous umbilical cord blood, as well as sensitivity to change in several ASD assessment tools, to determine suitable endpoints for future trials. Twenty-five children, median age 4.6 years (range 2.26–5.97), with a confirmed diagnosis of ASD and a qualified banked autologous umbilical cord blood unit, were enrolled. Children were evaluated with a battery of behavioral and functional tests immediately prior to cord blood infusion (baseline) and 6 and 12 months later.
Assessment of adverse events across the 12-month period indicated that the treatment was safe and well tolerated. Significant improvements in children’s behavior were observed on parent-report measures of social communication skills and autism symptoms, clinician ratings of overall autism symptom severity and degree of improvement, standardized measures of expressive vocabulary, and objective eye-tracking measures of children’s attention to social stimuli, indicating that these measures may be useful endpoints in future studies.
Behavioral improvements were observed during the first 6 months after infusion and were greater in children with higher baseline nonverbal intelligence quotients. These data will serve as the basis for future studies to determine the efficacy of umbilical cord blood infusions in children with ASD.
Human umbilical cord-derived mesenchymal stem/stromal cells: a promising candidate for the development of advanced therapy medicinal products
Umbilical cord-derived mesenchymal stem/stromal cells (UC-MSCs) emerge as a perspective for therapeutic use in immune and inflammatory diseases. Indeed, immunomodulatory and anti-inflammatory properties, associated to fewer ethical, availability, and safety issues, position UC-MSCs as a promising active substance to develop medicinal products. Since 2007, UC-MSC-based products are classified as advanced therapy medicinal products (ATMP) according to the European Regulation 1394/2007/EC. This new regulatory status required a total adaptation of stakeholders wishing to develop UC-MSC-based ATMPs.
Cell production in tissue and cell banks has been replaced by the manufacturing of a medicine, in authorized establishments, according to the good manufacturing practices (GMP) specific to ATMPs. After a brief description of UC-MSCs, we described in this review their recent use in a large panel of immune and inflammatory pathologies, including early and late phase clinical trials. Despite the use of the same product, we noticed an important heterogeneity in terms of indication, posology and study design.
Then, we discussed regulatory and manufacturing challenges for stakeholders, especially in terms of process harmonization and cells characterization. Our aim was to point that despite MSCs use for several decades, the development of an UC-MSC-based ATMP remains at this day a real challenge for both academic institutions and pharmaceutical companies.
Umbilical Cord Mesenchymal Stem Cells in Amyotrophic Lateral Sclerosis: an Original Study
Objective Amyotrophic lateral sclerosis (ALS) is still incurable. Although different therapies can affect the health and survival of patients. Our aim is to evaluate the effect of umbilical mesenchymal stem cells administrated intrathecally to patients with amyotrophic lateral sclerosis on disability development and survival. Methods This case-control study involved 67 patients treated with Wharton’s jelly mesenchymal stem cells (WJ-MSC). The treated patients were paired with 67 reference patients from the PRO-ACT database which contains patient records from 23 ALS clinical studies (phase 2/3). Patients in the treatment and reference groups were fully matched in terms of race, sex, onset of symptoms (bulbar/spinal), FT9 disease stage at the beginning of therapy and concomitant amyotrophic lateral sclerosis medications. Progression rates prior to treatment varied within a range of ± 0.5 points. All patients received three intrathecal injections of Wharton’s jelly-derived mesenchymal stem cells every two months at a dose of 30 × 106 cells. Patients were assessed using the ALSFRS-R scale. Survival times were followed-up until March 2020.
Results Median survival time increased two-fold in all groups. In terms of progression, three response types measured in ALSFRS-R were observed: decreased progression rate (n = 21, 31.3%), no change in progression rate (n = 33, 49.3%) and increased progression rate (n = 13, 19.4%). Risk-benefit ratios were favorable in all groups. No serious adverse drug reactions were observed.
Interpretation Wharton’s jelly-derived mesenchymal stem cells therapy is safe and effective in some ALS patients, regardless of the clinical features and demographic factors excluding sex. The female sex and a good therapeutic response to the first administration are significant predictors of efficacy following further administrations.
Randomized Assessment of the Safety and Efficacy of Intra-Arterial Infusion of Autologous Stem Cells in Subacute Ischemic Stroke
Stroke is a debilitating illness for which treatment window is limited. Most patients present to the healthcare facility beyond that window.Continue reading
Stem cell therapy for stress urinary incontinence
Stress urinary incontinence is the involuntary loss of urine on effort or physical exertion. It is a highly prevalent condition affecting both men and women. Treatment is performed in a step-wise approach involving conservative measures, such as weight loss and pelvic floor exercises, medical treatment with duloxetine and a variety of surgical treatment options.
However, recent restrictions in the use of synthetic mesh and tape have limited the surgical treatment options, leading to the need for new and novel treatment for stress urinary incontinence. Stem cell therapy is a developing medical field and offers the potential to restore normal physiological function of the urethral sphincter.
The effectiveness of stem cell therapy in stress urinary incontinence has been demonstrated in pre-clinical studies, leading to its evaluation in several clinical studies.
This review assesses the current evidence for the safety and efficacy of stem cell treatment for patients with stress urinary incontinence who have failed conservative and/or medical management and have not undergone previous surgical treatment for stress urinary incontinence.
Human mesenchymal stem cell treatment
of premature ovarian failure: new
challenges and opportunities
Premature ovarian failure (POF) is one of the common disorders found in women leading to 1% female infertility.Continue reading
Safety and efficacy of intracoronary treatment with umbilical cord-derived mesenchymal stem cells for very elderly patients with chronic total coronary occlusion
This study aimed to investigate the safety and feasibility of intracoronary injection of human umbilical cord-derived mesenchymal stem cells in very elderly patients with chronic total coronary occlusion into the coronary artery that provides collateral circulation to the heartContinue reading
Stem Cell Storage: Intermediary companies fail, but there are still Biobanks to rely on like SSCB
“The failure and mismanagement of other Biobanks for Stem Cell Preservation ruin our sector”, speaks Dr. Luca Mariotta, Scientific Director of SSCB.
Last week, Ticinonews reported on a young couple who were looking for their baby’s cells after the company they had contracted with, Genico, disappeared. Cantonal pharmacist Giovan Maria Zanini said he was concerned about Switzerland’s free-market policy in such a sensitive area.
50,000 stem cell transplants worldwide
More than 50,000 transplants have been performed worldwide using haematopoietic stem cells. Umbilical cord stem cells are multi-potent cells: unspecialised mother cells, capable of self-renewal and of differentiating into different cell types each with specific functions.Continue reading