CARDIOLOGY
Circulating Cast continued
The environmental connection
Aside from the cardiovascular system , the lateral plate mesoderm also gives rise to mesothelial cells , which provide a sort of protective shrink wrap for organs and produce mucous to lubricate them . Dr . Mosimann ’ s team isolated the first genetic program that sets them apart from other cells in the LPM . It ’ s the same program they use to repair themselves , after , say , a surgical incision .
And in the case of mesothelioma , a type of lung cancer triggered by asbestos fibers , Dr . Mosimann ’ s team found that it ’ s that same genetic program that goes awry .
“ It ’ s just an example of a way we can connect developmental biology to environmental factors , in this case asbestos exposure ,” says Dr . Mosimann . “ It ’ s a bigger story than just glow-in-the-dark fish .”
have problems with their joints and kidneys too .’ And our clinician colleages somewhere down the road can make those connections and make a care plan that improves that kid ’ s quality of life .”
FREE-FLOATING PREDICTORS
As clinicians , one of the most vexing problems Drs . Miyamoto and Nakano encounter in their patients is the unpredictable heterogeneity of outcomes . Some kids with , say , single ventricle heart disease do really well . With the help of three well-established operations that reconfigure their circulation , they can live long , relatively healthy lives .
Others ’ hearts ’ fail . That ’ s a growing public health problem , particularly as better treatments lead to longer survival for kids with serious heart anomalies ( 4 ). A transplant might last fifteen years . For a 2-year-old , that ’ s a lot of heart transplants down the road .
A much better solution would be to preserve the existing heart , but that ’ s a complicated problem to figure out . In the adult world , for example , many studies are done with biopsies . They ’ re relatively routine . For kids , whose hearts are much smaller , they ’ re intolerably risky . Dr . Miyamoto ’ s researchers get around that working with explanted tissues . But they ’ re also , increasingly , looking at the blood .
“ If we could predict who would do poorly that could help inform treatment ,” Dr . Miyamoto says . “ We ’ re trying to find cells and other
In color : the beginnings of the lateral plate mesoderm , developmental precursor to the heart and circulatory system . Photos by Hannah Moran
biomarkers that can do that , but we need to be able to get them from a blood draw .”
As she transitions from Dr . Miyamoto ’ s lab to independent research , Dr . Nakano is currently focused on those circulating biomarkers . In fact , last year she identified a set of circulating microRNAs that predicted survival or either transplant or death by one year of age .
She ’ s now investigating the potential role of the immune system through rigorous classification of the peripheral blood mononuclear cells , or PBMCs , in the blood of single ventricle patients on their way to surgery . Working with the Human Immune Monitoring Shared Resource , or HIMSR Core , a collaborative immunology lab on the Anschutz Campus , Dr . Nakano is working to define the types of immune cells in circulation , their activation status and what kind of cytokines they may produce .
“ In order to really figure out if a cell type works as a marker , if it ’ s a good surrogate for what ’ s happening in the heart ,” she says , “ you need to know exactly what you ’ re working with .”
And if that doesn ’ t work out , well , there are plenty of other fish in the sea . •
Cover photo by Hannah Moran ( left image ) and Christian Mosimann , PhD ( right image ).
1 . Nakano SJ , Walker JS , Walker LA , Li X , Du Y , Miyamoto SD , Sucharov CC , Garcia AM , Mitchell MB , Ambardekar AV , Stauffer BL . Increased myocyte calcium sensitivity in end-stage pediatric dilated cardiomyopathy . Am J Physiol Heart Circ Physiol . 2019 Dec 1 ; 317 ( 6 ): H1221-H1230 .
2 . Prummel KD , Nieuwenhuize S , Mosimann C . The lateral plate mesoderm . Development . 2020 Jun 19 ; 147 ( 12 ): dev175059 .
3 . Prummel , K . D ., Hess , C ., Nieuwenhuize , S . et al . A conserved regulatory program initiates lateral plate mesoderm emergence across chordates . Nat Commun 10 , 3857 ( 2019 ).
4 . Nakano SJ , Miyamoto SD , Price JF , Rossano JW , Cabrera AG . Pediatric Heart Failure : An Evolving Public Health Concern . J Pediatr . 2020 Mar ; 218:217-221 .
10 | CHILDREN ’ S HOSPITAL COLORADO