Interesting Research

The number of research publications involving stem cells has risen steadily over the past decade. Much of that research is based on animal models with the potential to progress into human studies at a later point. Some articles covering the early-stage clinical trials (primarily for neurodegenerative conditions) have also been featured in academic journals. However, often these studies lack the adequate sample size to validate the treatment protocol, were not placebo-controlled, or the patient profiles turned out to not be the right fit. Achieving progress can therefore be a slow-moving process and the ability to demonstrate efficacy for a specific medical condition can be time-consuming. With those observations in mind, listed below is some of the more promising research from the past couple of years.

Hearing Restoration In A Deaf Animal Model With Intravenous Transplantation Of Mesenchymal Stem Cells Derived From Human Umbilical Cord Blood

The ability to reverse the effects of an auditory insult using intravenously administered stem cells was demonstrated in this research publication from 2012. The animal-model showed that stem cells canmigrate to the cochlea when a sufficient quantity is employed. The result provides evidence that the more invasive procedures such as lumbar puncture or intratympanic injection can be avoided in the treatment of hearing loss. Together with similar published research from 2008, the outcome of this type of work formed the basis for the subsequent hearing loss study (in humans) that was conducted at the Florida Hospital for Children. The results of the 10-patient trial are still pending but should be available in 2018. However, a source affiliated with the investigation has already confirmed that positive outcomes were observed, but declined to elaborate on the specifics. So, it remains to be seen exactly what level of hearing improvement participants gained from the open-label intervention and whether all age groups benefited equally. But under the right circumstances, hearing loss is potentially already treatable today. [DOI Link]

Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial

The results of a double-blind placebo-controlled clinical trial for the treatment of acute ischemic stroke were published in the Lancet in 2017. The investigation had been ongoing for several years but failed to meet the primary efficacy endpoint (recovery measured at day-90, post-treatment). However, further analysis showed progressive improvement for treated patients up to one year as well as an improved outcome for those participants where intervention was performed within a 36-hour time window. The mechanism-of-action behind the allogeneic stem cell procedure relates to the role of the spleen which – in the slipstream of stroke – contributes to an increase of inflammation that leads to cell death. But the MultiStem-product employed in the study modulates the immune system response and is believed to enable a superior recovery provided the stem cells are administered early enough. In addition, those participants who were treated with MultiStem had a lower incidence of subsequent infection. The study sponsor – Athersys Inc – is planning a larger phase-III trial in the hopes of confirming the subpopulation results of the phase-II study. [DOI Link]

Long-term therapeutic effects of mesenchymal stem cells compared to dexamethasone on recurrent experimental autoimmune uveitis of rats

Published research from 2014 demonstrated how mesenchymal stem cells outperformed dexamethasone for the treatment of autoimmune uveitis. Besides their regenerative properties, MSCs are also known to be immunomodulatory – an important consideration for a number of medical conditions. The investigation showed that MSCs possess both a superior ability to suppress symptoms of relapsing uveitis but also a favourable safety profile. While the efficacy was evaluated during the acute-stage, other studies have looked into how MSCs perform when uveitis has become chronic. The administration of stem cells was done intravenously in the animal-model – thereby making it especially feasible for treatment in humans. [DOI Link]

Safety and Clinical Effects of Mesenchymal Stem Cells Secreting Neurotrophic Factor Transplantation in Patients With Amyotrophic Lateral Sclerosis: Results of Phase 1/2 and 2a Clinical Trials

In 2016, the results of two small-scale studies investigating stem cell therapy for the treatment of ALS were published. The trials relied on autologous mesenchymal stem cells (MSCs) that were expanded and modified to secrete neurotrophic growth factors. Through several treatment arms, it was then investigated to what extent the novel type of stem cells could halt disease progression in both patients with early- and advanced-stage ALS. While safety was the primary outcome of the studies, indications of efficacy were observed in those patients treated via the spinal cord administration route. A subsequent larger phase-II double-blind placebo-controlled trial confirmed clinically meaningful improvements in the 48-patient cohort. Based on the results, the study sponsor (BrainStorm Cell Therapeutics) initiated a phase-III trial in late 2017. The 200-patient clinical trial is expected to be completed in 2019 – read more via (use identifier: NCT03280056). [DOI Link]

Autologous Mesenchymal Stem Cells for the Treatment of Secondary Progressive Multiple Sclerosis: An Open-Label Phase 2A Proof-of-Concept Study

Research based on a small-scale clinical trial investigating stem cells for the treatment of progressive MS was published in The Lancet in 2012. The clinical trial was among the first to elucidate the potential efficacy of stem cells in the management of progressive MS, specifically. Administration of the autologous bone marrow-derived mesenchymal stem cells was done intravenously. Post-treatment, participants in the open-label trial saw indications of improvements of outcome endpoints concerning vision. Mesenchymal stem cells have the ability to differentiate and multiply; other mechanisms-of-action of MSCs relate to repair through the paracrine signalling effect. In the case, of progressive MS, it is believed that MSCs support remyelination of damaged nerve cells. Due to the size of the clinical trials and the heterogeneity of patient profiles, more work is required to confirm the efficacy of stem cells. A review of existing literature on clinical trials for the treatment of MS was published in 2017. [DOI Link]

Clinical Outcomes of Transplanted Modified Bone Marrow–Derived Mesenchymal Stem Cells in Stroke: A Phase 1/2a Study

A small-scale clinical trial investigating stem cells for the treatment of chronic ischemic stroke was conducted at the universities of Stanford and Pittsburgh. Patients enrolled in the study had plateaued in terms of their recovery, but upon receiving the modified stem cells through intracranial administration, they began experiencing further recovery. The encouraging outcome in terms of both safety and efficacy paved the way for a 2nd clinical trial (blinded) which will enroll a larger cohort of patients (see more via – use identifier: NCT02448641). The publication of results in 2016 led to significant media coverage and patient testimonials. A 2017-review on cell therapy for stroke recovery included a mention of the SB623 stem cells used in the joint Stanford-Pittsburgh trial. [DOI Link]

Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells

Following in the slipstream of an earlier investigation evaluating stem cells for the treatment of TBI in pediatric patients, the results of a similar study in adults were published in the journal, Stem Cells (in 2016). The small-scale study included control groups and provided indications of efficacy for the TBI-patients treated with autologous bone marrow-derived cells. The administration of cells was done intravenously in the acute phase of an injury to the brain. When an intervention with stem cells is done during this stage, it is believed that the mechanism-of-action lies with a reduction in the inflammation response that would otherwise remain elevated in untreated TBI-patients. Specifically, microglial activity is known to remain high long after the initial injury and hence contribute to an impaired recovery. This initial trial paved the way for a larger phase-IIb blinded placebo-controlled study (see more via – use identifier NCT02525432). [DOI Link]

Clinical Trial of Human Umbilical Cord Blood-Derived Stem Cells for the Treatment of Moderate-to-Severe Atopic Dermatitis: Phase I/IIa Studies

The results of a first-in-class study employing allogeneic stem cell transplantation for the treatment of eczema were published in 2016. As a phase-I/IIa with dose-escalation, a differentiated response was observed in the treatment cohorts: 55% patients who received the larger dose gained 50% reduction in the so-called EASI-score (lasting through the end of the trial). The improvement in severity of symptoms was correlated with a reduction in the evaluated biomarkers included in the study. No adverse events encountered. The stem cells were administered subcutaneously. Further studies are planned to accommodate the lack of placebo and small sample size. [DOI Link]

Intra-Articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritis of the Knee: A Proof-of-Concept Clinical Trial

Using stem cells for the treatment of osteoarthritis was investigated in a small-scale study that saw the publication of results in 2014. The study design included dose-escalation with three cohorts for each increasing dosage. The cell source was autologous from adipose tissue through a liposuction procedure. Mesenchymal stem cells were isolated and administered into the affected joint. Post-treatment. patients reported increased knee function and reduced pain with no adverse events encountered in the study. The mechanism-of-action in the case of joint repair is believed to be through differentiation of MSCs into chondrocytes as well as through the paracrine signalling effect. Other studies employing a similar approach are underway (see – use identifiers NCT03014401 and NCT03308006). [DOI Link]