SickKids-led research demonstrates first use of exosomes as fetal therapy using animal models and human lung cells

Posted on April 21, 2021

Summary:

International research team used exosomes from amniotic fluid stem cells in animal models and human lung cells to treat underdeveloped fetal lungs, restarting growth and normal functioning.

An international team of researchers led by The Hospital for Sick Children (SickKids) has successfully demonstrated the potential of exosomes as a fetal therapy to regenerate immature lungs. Exosomes, which can be thought of as messengers carrying genetic material that travel between cells, have emerged as having therapeutic potential for a wide range of diseases in adults, including cancer and heart conditions.

Now, the SickKids-led research team has demonstrated that exosomes from stem cells isolated in the amniotic fluid can successfully regenerate fetal lung growth and maturation in animal models and human lung cells. Their findings were published in Science Translational Medicine on April 21, 2021. The researchers say their study highlights how exosomes could be a vital precision medicine tool for paediatrics in the future.

Dr. Augusto Zani, principal investigator of the study, Neonatal and Paediatric Surgeon in the Division of General and Thoracic Surgery, and Scientist in the Developmental and Stem Cell Biology program, SickKids, and Lina Antounians, first author of the study, Lab Research Project Manager in the Developmental and Stem Cell Biology program, SickKids, discuss their work and how their findings could have the potential to treat several kinds of congenital abnormalities.

Breathing is essential to life, as with every breath, the body is replenished and cleansed, a process made possible by the lungs.

Every year, in the US and Canada alone, almost 2,000 babies are born with lungs that are too small for them to breath properly. Tragically, half of the babies dies, and the other half has severe difficulty breathing.

These babies suffer from a condition called Congenital Diaphragmatic Hernia or CDH, as they are born with a hole in diaphragm, the muscle that separates the chest from the belly. So, the organs that are supposed to live in the belly, such as the intestines, slip up through the hole into the chest and squash the lungs to a point that they don’t have enough room to grow.

Even when we do surgery to close the hole in the diaphragm and return the bowels into the belly, the lungs remain way too small. We all agree that a therapy for these tiny lungs is desperately needed.

Once the baby is born, it’s too late to make the lungs grow. The good thing is that nowadays we can recognize these babies with CDH before birth, with a simple ultrasound scan. So, we all agree that the ideal timing to intervene on these lungs is when the baby is still in the mom’s womb. However, many research groups have tried, but none of the treatments tested so far has been successful.

I am very excited to tell you that we think we have found the solution in the amniotic fluid!

For years, we have been studying stem cells from the amniotic fluid and we have now demonstrated that they release small droplets, called exosomes, that can make the tiny lungs grow bigger!

Exosomes are like postmen who carry messages from a cell to another. They are released by all cells, but those coming from the amniotic fluid are special as they can regenerate organs, like the lung of a baby. In fact, they carry a message made of genetic material, the so-called microRNAs, molecules that tell the recipient lung cell to restart growing.

When in our studies we gave exosomes to tiny lungs, we observed they restarted growing and functioning like normal.

When we coloured the exosomes to see where they were going, we found them inside the lung cells and saw that they released their cargo.

This caused the lung cells to make more and more of the molecules that help us breathe, like surfactant, and we saw that the treated lungs were more mature as they had more specialized cells.

I am very excited because this is the first fetal therapy using exosomes! Our study opens avenues to test the use of these exosomes for other congenital anomalies. This means increasing the chances for millions of babies to survive and live a normal life.