Nanoparticles, Fetal Therapy, & Pediatric Surgery - The Stitelman Lab at Yale School of Medicine

Transcript

• 00:05The fetus is a fascinating patient.
• 00:08They have many accessible and developing stem cell populations
• 00:12that are gone once the baby is born.
• 00:15Historically, if you do fetal surgery where you operate on a fetus,
• 00:20the wound heals with no scar.
• 00:22So it's a very different patient than even a baby.
• 00:26And so the idea that you could get organs to grow more normally while they're
• 00:32in the process of becoming the organs that they're going to be is compelling.
• 00:40Our lab is looking at ways to
• 00:43treat and cure genetic and structural diseases before birth.
• 00:47The clinical practice in pediatric surgery
• 00:50is babies who are born with a variety of needs.
• 00:53So babies whose abdominal walls don't form normally
• 00:57or diaphragms don't form normally
• 00:58or lungs, guts and airways that don't form normally,
• 01:01and some of these things are diagnosed before birth
• 01:04and that's a window to allow the baby to develop normally,
• 01:09if you can correct problem.
• 01:15So our work is a collaboration with biomedical engineering
• 01:18and molecular therapy at Yale,
• 01:20and we deliver therapeutic agents in very small particles
• 01:24to try to treat genetic or structural diseases before birth.
• 01:28The first part of it is synthesizing those particles
• 01:32using a variety of techniques to verify that they're good quality,
• 01:36and that they are loaded with the things that you think that they're loaded with.
• 01:40We're able to deliver those particles to fetuses in experimental models
• 01:45and then there's one round of analysis, which is where are the particles going?
• 01:50So that's typically microscopy or flow cytometry,
• 01:54and then if you're trying to rescue a disease model then
• 01:57the analysis depends on the model that you're looking.
• 02:00They're projects where we're looking at lung growth,
• 02:03techniques to to assess those are microscopy functional assays
• 02:06and we've actually started to get into more sophisticated molecular techniques
• 02:10like single cell RNA sequencing and spatialomics
• 02:14where you can really try to understand
• 02:16the interactions between the cells in normal fetal development,
• 02:19and then the interactions of those cells when there's abnormal fetal development.
• 02:27With the spectrum of things that we're working in the lab,
• 02:30you could provide a single shot
• 02:32that would cure a variety of genetic diseases.
• 02:35So lysosomal storage diseases,
• 02:38diseases of the brain, cystic fibrosis, blood diseases.
• 02:41You may be able to have a single shot
• 02:43and cure a genetic disease for the duration of that patient's lifetime.
• 02:48Other strategies that are a little bit newer for our lab,
• 02:5145% of neonatal death
• 02:54is due to these issues of prematurity
• 02:57and if you could improve the health and function of the tissues that support a healthy pregnancy,
• 03:02then you may be able to drastically move the needle
• 03:05on these sort of major public health problems.