Amniotic liquid undifferentiated cells may prompt better treatment for ischemic stroke

Overview

• Post By : Kumar Jeetendra


• Source: AlphaMed Press


• Date: 07 Oct,2020

A study published today in STEM CELLS Translational Medicine points the way to a potential new avenue of treatment for ischemic stroke.

The study, led by Annamaria Cimini, Ph.D., of the University of L’Aquila, and Liborio Stuppia, M.D., of D’Annunzio University, Italy, shows how the secretome of amniotic fluid stem cells can restore neuronal plasticity (the brain’s capacity to change and adapt), improve cognition, and replace nerves damaged or lost because of an ischemic stroke.

Their finding may lead to a more broadly applicable stroke treatment that is not hindered by a narrow treatment window or pre-existing conditions.

When we examined the results, we found that the hAFSC-derived secretome had activated pro-survival pathways, as well as pathways that halted apoptosis (programmed cell death). Furthermore, microRNA analysis in the exosomal component revealed an abundance of miRNAs involved in protecting neurons and controlling neuronal cell death.”-Liborio Stuppia, M.D., D’Annunzio University, Italy

Each year, 5.5 million people across the world die from stroke, and over 116 million years of healthy life are lost as a result of stroke-related disabilities and death, according to the World Stroke Organization. Most strokes – an estimated 87 percent – are the ischemic type, which occur when a vessel supplying blood to the brain becomes obstructed.

The very best treatment currently in use is a clot-busting medication known as a tissue plasminogen activator (t-PA). However, to succeed the t-PA must be given within three hours after the onset of stroke symptoms, and even then the treatment rate is one in 10 patients. T-PAs have their own dangers, especially for men and women who have a history of bleeding problems, uncontrolled high blood pressure, or recent surgery or injury.

“Thrombolytic treatment itself may lead to brain injuries, namely cerebral ischemia/reperfusion (I/R) injury. I/R injury is among the major reasons for disability, high morbidity, and mortality globally,” Dr. Cimini said. (Reperfusion denotes the act of restoring the flow of blood to an organ or tissue, typically after a heart attack or stroke.)

In the search for improved treatment options, stem cells have emerged as a possible candidate due to their regenerative abilities. Human amniotic fluid stem cells (hAFSCs) in particular are interesting, as adult stem cells – even after reprogramming – might pass along any pre-existing genetic conditions, thus representing a limitation in their application.

On the other hand, hAFSCs offer a clean curative slate. Furthermore, ethical issues related to their use are minimal, as they’re gathered during routine amniocentesis, third-trimester amnio-reduction or Cesarean section.

The growing interest in hAFSCs within the past decade has led researchers to also investigate the cells’ secretome – that encompasses the complete set of proteins expressed by cells and secreted into the extracellular space – and its potential neuroprotective mechanisms.

In their current study, the Cimini- Stuppia team wanted to ascertain which signal transduction pathways may be activated by hAFSC-derived secretome during a stroke. (Signal transduction is how signals are transferred through a mobile via proteins – a process necessary for recovery.)

They also wanted to analyze miRNA expression in the conditioned medium. MiRNAs found in exosomes are key regulators of the immune response that influence maturation, proliferation, differentiation and activation of immune cells, as well as antibody secretion and release of inflammatory mediators.

“Thus, exosomes offer an alternative therapeutic approach for a substitute for cell transplantation,” Dr. Cimini said.

The team began by first devising an in vitro stroke model. To do so, they deprived hAFSCs of oxygen and sugar for a three hour period after testing several different time windows – in three hours, the cells showed a reduction in viability of roughly 50 percent. Then, 24 hours later, they treated the oxygen/glucose depleted cells with a number of different percentages of hAFSC-conditioned medium.

“In light of the information obtained, we believe that the use of conditioned medium and, in particular, exosomes may represent a suitable treatment for I/R injury,” he reasoned.

“These early pre-clinical results are certainly encouraging and demonstrate the need to further pursue human amniotic fluid stem cells-derived secretome as a regenerative cell therapy,” said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “These results suggest a possible approach that could alter the outcome for millions of patients who suffer a stroke.”