Stem Cells for Covid-19: Hype or Hope

Written by: Professor Datuk Dr. A Rahman A Jamal, Senior Principal Research Fellow, UMBI

Date published: 23rd April 2020

It has been 5 days since I posted about Covid-19. This one is a bit technical but I hope it will be simple enough for the public layperson to understand. Everyone is looking for an effective treatment for Covid-19 infection especially for those very sick ones in intensive care and requiring respiratory support. There are the anti-viral therapies and drugs such as hydroxychloroquine which have shown promising results. In the past few weeks, stem cells have entered the ring. Stem cells are the mother cells from which all other cells are derived. Mesenchymal stem cells (MSCs) are a type of stem cells which can be obtained from bone marrow or umbilical cord blood. The interest for MSCs in the treatment for Covid-19 began with the first reported case where a 65-year-old patient in China in ICU was given three infusions of 50 million MSCs (derived from human umbilical cord blood) 3 days apart. She made full recovery. In medicine, one case is considered anecdotal in nature, nevertheless, this case attracted attention and triggered it all. The next report came very soon and this time seven patients were treated (one critically ill, 4 severe cases and 2 non-severe cases). All patients received a single dose of 1 million cells per kg body weight. The results were positive in all cases and no adverse events were recorded and all the main inflammatory markers decreased.

The basis for treatment using MSCs is simple and attractive. MSCs is considered an immunomodulatory and anti-inflammatory agent. In Covid-19 patients with pneumonia, it is believed that the acute respiratory distress syndrome (ARDS) is caused by the overwhelming presence of a cytokine storm with widespread inflammation. MSCs when given are believed to home in to the lungs and counter the inflammation quickly and effectively. Magical right? Sounds like good science too. But let’s not make a quick conclusion.

Since the case report and the cases series involving the 7 patients, many stem cell researchers all over the world are embarking on clinical trials of MSCs. More than 20 clinical trials using MSCs have been registered worldwide. The FDA itself has approved a 24-patient clinical trials to test the safety and efficacy of UC-MSCs (from umbilical cord) based at the University of Miami Health System. The University of Texas also recently announced a Phase 2B randomised trial using BM-MSCs (from bone marrow), with the aim to recruit 120 patients. The bulk of clinical trials are in China.

However, not everyone is impressed, even top professors and researchers working with stem cells and regenerative medicine (many reviews and comments available online). Some of them say the stem cell studies are small and many are conducted without controls (a group of patients not given stem cell therapy but given standard treatment so that efficacy can be compared). Some say the therapeutic effect of MSCs on any clinical condition (other than Covid-19) has not be shown convincingly.

As doctors, we have vowed to do no harm, and not to subject sick and vulnerable patients to unnecessary studies. MSCs may sound very fashionable but the rush to test for the best treatment should not be done at the expense of rigorous science. Many of the clinical trials do not have a control arm; hence, the likelihood for false positives (stating a good outcome when in fact the same outcome will happen even without MSC treatment) and over-interpretation is high. Even those clinical trials with a control arm are mostly underpowered. Many of us doctors were taught statistics, sampling, sample size, effect size and study power. Those conducting clinical trials are also trained in Good Clinical Practice. We should not forget these principles of good experimental approach and study design. Poor design will allow for the opportunity for bias hence giving false results and worse, false hopes, whilst wasting public funding and resource.

My take on this is simple. There is a need to show and prove clearly the science first before embarking on human studies. For the Covid-19 trials, somehow many are bypassing the pre-clinical studies in the name of emergency and compassion. Quoting the safety evidence from other studies is easy, but for many ethics committees, it is a requirement that this should be shown from the research team’s own research work. The clinical trials design must state clearly outcomes related to safety and efficacy. The trials should have enough number of patients and should be at multiple site (again to avoid bias), and standardisation of protocols is a must including dosing (how many million cells to give and how many infusions). There is hope and potential of MSCs, but we cannot rush things through at the expense of good science and research quality.

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