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Diabetes mellitus (DM) is a terribly growing epidemic, currently affecting about 463 million people worldwide, with expected rise to 700 million by the year 2045.

It is the most prevalent metabolic disease, in which insulin secreting β cells are damaged to various extents. Different etiologies and interfering factors exist for each of type 1 and type 2 DM (T1DM and T2DM), the most famous well-known types. However, β cell dysfunction and hyperglycemia are disease hall-marks for both types, and diabetic complications, as well as decreased life quality and increased mortality are unfortunately inevitable in most cases. Accordingly, there is an urgent need to develop novel therapeutic modalities which would help not only to manage the disease, but also hopefully provide a real cure for DM. Regenerative medicine and stem cell therapy opened new avenues and ignited much hope for patients with DM over the past few years.

Various types of stem cells have been investigated regarding their therapeutic potential for DM in the preclinical as well as clinical settings. Interestingly, among the various sources of stem cells, the umbilical cord (UC) has proved to be a unique source, providing several advantages over other sources. Most importantly, UC-derived stem cells are readily available and can be obtained non-invasively during the process of delivery. Moreover, their banking potential adds a lot to their importance for regenerative medicine.

Several previous meta-analyses concluded the safety as well as therapeutic efficacy of stem cell therapy in DM. Nevertheless, published meta-analyses mostly combined studies which applied MSCs derived from various sources including the bone marrow-MSCs, placenta-MSCs, as well as WJ-MSCs together, and some also combined UCB together with peripheral blood mononuclear cells (PB-MNCs), or included studies which employed UCB transplantation, together with those employing “stem cell educator” therapy. While others pooled all different types of stem cell therapies together including UCB, WJ-MSCs, as well as HSCs and other types of MSCs. Additionally, previously, we compared the therapeutic effect of WJ-MSCs and UCB-derived MSCs in streptozotocin-induced diabetic rats. Interestingly, we found that WJ-MSCs can better control hyperglycemia in diabetic rats in vivo and also better differentiate into insulin producing cells in vitro, as compared with UCB-MSCs.

The results of the current study also shed lights on the importance to consider cryopreservation/banking of WJ-MSCs together with the well-established routine banking of UCB, especially for those with family history of DM. Additionally, the current study highlights the crucial need for additional well-designed randomized controlled trials with larger cohorts, in order to fill the obvious gap between pre-clinical and clinical studies. Undoubtedly, the future will unravel much more findings concerned with the therapeutic mechanisms of action, as well as methods to maximize the therapeutic benefits of WJ-MSCs.

COMPLETE STUDY>> stemcellres.biomedcentral.com/articles/10.1186/s13287-020-01996-x

A new study led by UC Davis MIND Institute researchers found a distinct DNA methylation signature in the cord blood of newborns who were eventually diagnosed with autism spectrum disorder (ASD). This signature mark spanned DNA regions and genes linked to early fetal neurodevelopment. The findings may hold clues for early diagnosis and intervention.

The researchers studied the development of 152 children born to mothers enrolled in the MARBLES and EARLI studies. These mothers had at least one older child with autism and were considered at high risk of having another child with ASD. When these children were born, the mothers’ umbilical cord blood samples were preserved for analysis. At 36 months, these children got diagnostic and developmental assessments. Based on these, the researchers grouped the children under “typically developing” (TD) or “with ASD.”

The researchers also analyzed the umbilical cord blood samples taken at birth from the delivering mothers. They performed whole-genome sequencing of these blood samples to identify an epigenomic signature or mark of ASD at birth. They were checking for any patterns of DNA-epigenome binding that could predict future ASD diagnosis.

The researchers identified DMRs stratified by sex that discriminated ASD from TD cord blood samples in discovery and replication sets. They found that seven regions in males and 31 in females replicated, and 537 DMR genes in males and 1762 DMR genes in females replicated by gene association. These DMRs identified in cord blood overlapped with binding sites relevant to fetal brain development. They showed brain and embryonic expression and X chromosome location and matched with prior epigenetic studies of ASD.

“Findings from our study provide key insights for early diagnosis and intervention,” LaSalle said. “We were impressed by the ability of cord blood to reveal insights into genes and pathways relevant to the fetal brain.”

The researchers pointed out that these results will require further replication before being used diagnostically. Their study serves as an important proof of principle that the cord blood methylome is informative about future ASD risk.

+INFO www.newswise.com/articles/cord-blood-dna-can-hold-clues-for-early-asd-diagnosis-and-intervention

CLINICAL TRIAL genomemedicine.biomedcentral.com/articles/10.1186/s13073-020-00785-8

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.

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.

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.

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.

Keeping in mind the study limitation, our results suggest that treatment with MSC substantially reduces the rate of progression and yields a twofold extension of survival in those who achieved a positive response to the first administration in comparison to the reference subject.

These HR values were even better than those achieved with the registered drug, edaravone. Demographic factors have a certain impact on the risk-benefit ratio, so they should be discussed with the patient before the start of therapy. MSC administration was absolutely safe. Eligibility for the treatment should be confirmed following first administration based on the progression rate in comparison with at least one reference subject (more would be beneficial). Future studies should focus on confirming these observations in double-blind, controlled studies, optimally with a three-arm design to investigate additive or synergic effects with edaravone.

CLINICAL STUDY link.springer.com/article/10.1007/s12015-020-10016-7?elqTrackId=e04512242c98421ba643066ab0c83a41

In the attempt to find a possible cure for Alzheimer’s disease (AD), mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) are being investigated for therapeutic purposes thanks to their protective and anti‐inflammatory properties. The results from this study show that MSC‐EVs operate in dampening inflammation (that favors and accelerates the pathogenic process in AD) and in inducing neuroprotective effects. Furthermore, they sustain the delivery of MSC‐EVs through the intranasal route, being safe and low invasive, thus laying the foundation for a translational future exploitation of MSC‐EVs toward therapy.

Alzheimer’s disease (AD), the most common form of age‐related dementia, is characterized by a slow progressive and detrimental degeneration of the central nervous system (CNS). Neuropathological hallmarks of AD are extracellular β‐amyloid plaques, neurofibrillary tangles, inflammation, synaptic and neuronal dysfunction, and degeneration.1 Inflammation, a concurrent etiopathological mechanisms in AD, is primarily orchestrated by microglia, which represent the innate immune cells of the CNS. They exert also regulatory roles on synaptic plasticity, interacting with neurons by cell‐to‐cell contact or by secreting mediators,2, 3 thus contributing to the remodeling of neural circuits and being involved in learning and memory processes.4

In order to rapidly respond to minimal changes of brain microenvironment, microglia are plastically capable of adopting different and complex activation states, which allow them to contribute either to the cytotoxic response, or to injury resolution and tissue repair.5, 6

CLINICAL TRIAL https://stemcellsjournals.onlinelibrary.wiley.com/

Studies suggest that the use of mesenchymal stem cells collected from umbilical cord blood and tissue are a safe and effective way to alleviate symptoms of coronavirus and promote fast recovery.

Recently, mesenchymal stem cells (MSCs) harvested from umbilical cord blood have attracted significant attention in clinical trials for COVID-19 due to their immunomodulatory and regenerative properties.

When an individual contracts COVID-19, an immune overreaction is triggered in the body, producing large amounts of inflammatory factors whilst simultaneously destroying numerous essential cells. This results in in an overproduction of immune cells and cytokines, which researchers refer to as an “inflammatory storm”.

Here, the idea to use MSCs in the treatment of COVID-19 patients was coined, to prevent the storm release of cytokines by the immune system and promote repair by reparative properties of the stem cells.

These MSCs oppose viral infections due to the presence of specific cytokines improved qualities. Subsequently, they can prevent lung tissue damage by counteracting the cytokine storm through their immunomodulatory function and differentiation ability to regenerate and reconstruct damaged tissue. As a result, it has been demonstrated that MSCs significantly reduce the risk of COVID-19 pneumonia and respiratory failure.

The application of these stem cells seems to be particularly effective in cases of critically ill patients, as reported in the Aging and Disease journal. In this study, seven COVID-19 patients were administered with MSCs from the umbilical cord. After two days of receiving the MSC treatment, the pulmonary function and symptoms of the seven patients were significantly improved without any adverse effects.

INFO www.openaccessgovernment.org

CLINICAL TRIALS WITH MESENCHYMAL CELLS IN COVID19

clinicaltrials.gov

A team of researchers at the Washington University School of Medicine in St. Louis have converted human stem cells into insulin-producing cells, controlling the blood sugar levels of laboratory mice. Within just nine months, the mice had been cured of diabetes, hinting that the procedure may be used in humans to cure diabetes.

Published in the journal Nature Biotechnology, the study shows promise in the treatment of chronic diabetes, especially in people with poorly controlled blood sugar levels. The findings of the study could pave the way for developing a novel therapy for treating type 1 and type 2 diabetes.

The use of human stem cells has shown promise in various fields in medicine. The current research was build up from a previous study, wherein the same researchers have found that they can convert human stem cells into pancreatic beta cells to produce insulin. The cells, when they encounter blood sugar, release insulin. In turn, it will control blood sugar levels, even when the patient has a faulty pancreas and a low supply of insulin.

Insulin is a hormone made by the pancreas allowing the body to use glucose or sugar from carbohydrates in the food or to store it for future use. It also maintains blood sugar levels in the body, preventing it from shooting up (hyperglycemia) or going too low (hypoglycemia).

In the current study, the researchers have shown a new method that can more effectively convert human stem cells into insulin-producing cells that can efficiently control blood sugar. The team found that fewer ‘off-target’ cells were produced, and the beta cells that were made had improved function.

The new method targets the cells’ internal scaffolding, dubbed as the cytoskeleton, which gives the cell its shape and allows the cell to interact with the environment.

https://www.nature.com/articles/s41587-020-0430-6.epdf?referrer_access_token=faC8XuxPyidxJMmyL6vXedRgN0jAjWel9jnR3ZoTv0NrfJgRLJqJDJja_WP1AoRFgl2zYrganVQtS0_jK-Cxr0J3-lPMwivynFZjKLH3fapMN_dNGzFdAMG_uh3vsrySCEF88YNMhuJvxHSNhqIuh-9MxUQNfclICtjk1-fRA_jIWMGWitea78_IVIJiwlArkPWOpdY-ChMLKDM-DKKpaQ%3D%3D&tracking_referrer=www.iflscience.com

Last March, scientists announced that Mr. Castillejo, then identified only as the “London Patient,” had been cured of H.I.V. after receiving a bone-marrow transplant for his lymphoma. The donor carried a mutation that impeded the ability of H.I.V. to enter cells, so the transplant essentially replaced Mr. Castillejo’s immune system with one resistant to the virus. The approach, though effective in his case, was intended to cure his cancer and is not a practical option for the widespread curing of H.I.V. because of the risks involved.

Only one other individual with H.I.V. — Timothy Ray Brown, the so-called Berlin Patient, in 2008 — has been successfully cured, and there have been many failed attempts. In fact, Mr. Castillejo’s doctors could not be sure last spring that he was truly rid of H.I.V., and they tiptoed around the word “cure,” instead referring to it as a “remission.”

MORE INFO www.nytimes.com/

Preterm birth and its complications are the leading cause of neonatal death. The main underlying pathological mechanisms for preterm complications are disruption of the normal maturation processes within the target tissues, interrupted by premature birth. Cord blood, as a new and convenient source of stem cells, may provide new, promising options for preventing preterm complications. This prospective, nonrandomized placebo controlled study aimed at investigating the effect of autologous cord blood mononuclear cells (ACBMNC) for preventing preterm associated complications.

The results from this prospective nonrandomized study foundthat autologous cord blood cells infusion substantially reduced the duration of mechanical ventilation and oxygensupplement. Fewer preterm complications were observed inthe cord blood cell infusion group, although there was no sig-nificant difference. Preterm birth complications are the firstmajor direct cause of neonatal death, and no curative thera-pies are available to alleviate the symptoms of preterm com-plications. Stem cells as a treatment provides regrowth totheir underdeveloped organs and therefore could improve theoutcomes of preterm infants by adding more stem/progenitorcells. This may be helpful to prevent preterm complications.

MORE INFO stemcellsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/sctm.19-0106