Regenerative Medicine and Stem Cells Technologies

A preclinical study conducted by researchers at Sungkyunkwan University (Seoul, South Korea) has

indicated that extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) could alleviate intraventricular hemorrhage (IVH) damage – a devastating condition that commonly affects premature babies.

Their research was recently published in the journal STEM CELLS Translational Medicine.

Severe IVH can cause a build-up of fluid in the brain, resulting in an increase in pressure that can lead to seizures, cerebral palsy, developmental retardation and an increased mortality rate. Up until now, there have been no promising treatments for this disease on the horizon.

MSCs have the ability to produce biologically active molecules that have regenerative effects on the body – making them an ideal asset in regenerative therapy. However, transplantation with these cells gives rise to a few concerns – including the potential to form tumors, cause pulmonary embolisms, or a chance of the cells being rejected.

In their study, the team used MSC-derived EVs to target IVH in rats. These membranes containing proteins, lipids and RNAs can recreate the therapeutic activity of their parent MSC – whilst avoiding the associated safety concerns.

“This all has led to the questions of whether MSC-derived EVs might serve as a surrogate for stem cell therapy in cases of severe IVH and, if so, whether the neuroprotection is related to protein transfer from EVs to the damaged host brain tissue,” commented the study’s corresponding author, Won Soon Park (Sungkyunkwan University).

In their experiments, the team discovered that the therapeutic EVs transferred a protein-coding gene called BDNF, which is likely to be responsible for the neuroprotection seen.

Both MSCs and MSC-derived EVs with or without BDNF knockdown, or fibroblast-derived EVs were administered in vitro to thrombin-exposed rat neuronal cells. This procedure was also repeated in vivo on 4-day old rats.

“We learned that the MSCs and MSC-derived EVs – but not the EVs derived from BDNF-knockdown MSCs or fibroblasts – significantly reduced both the thrombin-induced neuronal cell death in vitro and the severe IVH-induced brain injuries and inflammatory responses in vivo,” Park explained. “As such, our data indicate that MSC-derived EVs are as effective as parental MSCs in attenuating severe IVH-induced brain injuries, and this neuroprotection is primarily mediated by BDNF transfer via EVs. We hope now to move on to establishing the optimal timing, route and dosage of the MSC-derived EVs.”

“The promising potential of MSC derivatives are highlighted in this early study for a treatment for bleeding in the brain, a common occurrence in premature babies,” concluded Anthony Atala, Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine (NC, USA). “This approach offers hope someday of a treatment to prevent or reduce the devastating effects of brain hemorrhage that can cause seizures, developmental delay and death in these vulnerable babies.”