Therapeutic Role of Mesenchymal Stem Cell Derived Extracellular Vesicles in Female Reproductive Diseases


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.

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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Cell production in tissue and cell banks has been replaced by the manufacturing of a medicine, in authorized establishments, according to the good manufacturing practices (GMP) specific to ATMPs.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.

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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.

Significant Improvement of Acute Complete Spinal Cord Injury Patients Diagnosed by a Combined Criteria Implanted with NeuroRegen Scaffolds and Mesenchymal Stem Cells


Stem cells and biomaterials transplantation hold a promising treatment for functional recovery in spinal cord injury (SCI) animal models. However, the functional recovery of complete SCI patients was still a huge challenge in clinic. Additionally, there is no clinical standard procedure available to diagnose precisely an acute patient as complete SCI. Here, two acute SCI patients, with injury at thoracic 11 (T11) and cervical 4 (C4) level respectively, were judged as complete injury by a stricter method combined with American Spinal Injury Association (ASIA) Impairment Scale, magnetic resonance imaging (MRI) and nerve electrophysiology. Collagen scaffolds, named NeuroRegen scaffolds, with human umbilical cord mesenchymal stem cells (MSCs) were transplanted into the injury site. During 1 year follow up, no obvious adverse symptoms related to the functional scaffolds implantation were found after treatment. The recovery of the sensory and motor functions was observed in the two patients. The sensory level expanded below the injury level, and the patients regained the sense function in bowel and bladder. The thoracic SCI patient could walk voluntary with the hip under the help of brace. The cervical SCI patient could raise his lower legs against the gravity in the wheelchair and shake his toes under control. The injury status of the two patients was improved from ASIA A complete injury to ASIA C incomplete injury.
Furthermore, the improvement of sensory and motor functions was accompanied with the recovery of the interrupted neural conduction. These results showed that the supraspinal control of movements below the injury was regained by functional scaffolds implantation in the two patients who were judged as the complete injury with combined criteria, it suggested that functional scaffolds transplantation could serve as an effective treatment for acute complete SCI patients.

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Stem cell therapy for stress urinary incontinence

stem cells urinary

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.

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Clinical feasibility of umbilical cord
tissue-derived mesenchymal stem cells
in the treatment of multiple sclerosis

stem cells multiple sclerosis

Multiple sclerosis (MS) is a progressively debilitating neurological condition in which the immune system abnormally erodes the myelin sheath insulating the nerves. Mesenchymal stem cells (MSC) have been used in the last decade to safely treat certain immune and infammatory conditions.

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Safety and efficacy of intracoronary human umbilical cord-derived mesenchymal stem cell treatment for very old patients with coronary chronic total occlusion

stem cells coronary chronic total occlusion

This study aimed to investigate the safety and feasibility of intracoronary injection of human umbilical cord mesenchymal stem cell to the very old patients with coronary chronic total occlusion 15 consecutive patients received mesenchymal stem cells from human umbilical cord in epicardial coronary artery supplying collateral circulation.

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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.

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