Circulating trophoblast cell clusters for early detection of placenta accreta spectrum disorders

Yalda Afshar; Jiantong Dong; Pan Zhao; Lei Li; Shan Wang; Ryan Y Zhang; Ceng Zhang; Ophelia Yin; Christina S Han; Brett D Einerson; Tania L Gonzalez; Huirong Zhang; Anqi Zhou; Zhuo Yang; Shih-Jie Chou; Na Sun; Ju Cheng; Henan Zhu; Jing Wang; Tiffany X Zhang; Yi-Te Lee; Jasmine J Wang; Pai-Chi Teng; Peng Yang; Dongping Qi; Meiping Zhao; Myung-Shin Sim; Ruilian Zhe; Jeffrey D Goldstein; John Williams 3rd; Xietong Wang; Qingying Zhang; Lawrence D Platt; Chang Zou; Margareta D Pisarska; Hsian-Rong Tseng; Yazhen Zhu

doi:10.1038/s41467-021-24627-2

Circulating trophoblast cell clusters for early detection of placenta accreta spectrum disorders

Nat Commun. 2021 Aug 3;12(1):4408. doi: 10.1038/s41467-021-24627-2.

Authors

Yalda Afshar^#¹, Jiantong Dong^#^{2

3}, Pan Zhao⁴, Lei Li^{2

5}, Shan Wang^{2

5}, Ryan Y Zhang², Ceng Zhang², Ophelia Yin¹, Christina S Han^{1

6}, Brett D Einerson⁷, Tania L Gonzalez⁸, Huirong Zhang⁴, Anqi Zhou², Zhuo Yang², Shih-Jie Chou², Na Sun², Ju Cheng², Henan Zhu², Jing Wang², Tiffany X Zhang², Yi-Te Lee², Jasmine J Wang⁹, Pai-Chi Teng⁹, Peng Yang², Dongping Qi², Meiping Zhao³, Myung-Shin Sim¹⁰, Ruilian Zhe⁴, Jeffrey D Goldstein¹¹, John Williams 3rd⁸, Xietong Wang⁵, Qingying Zhang^{2

12}, Lawrence D Platt^{1

6}, Chang Zou¹³, Margareta D Pisarska¹⁴, Hsian-Rong Tseng¹⁵, Yazhen Zhu¹⁶

Affiliations

¹ Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
² California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
³ Beijing National Laboratory for Molecular Sciences, MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
⁴ Clinical Medical Research Center, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong, China.
⁵ Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
⁶ Center for Fetal Medicine and Women's Ultrasound, Los Angeles, CA, USA.
⁷ Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, University of Utah Health, Salt Lake City, UT, USA.
⁸ Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁹ Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁰ Departments of Computational Medicine & Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹¹ Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹² Department of Obstetrics, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
¹³ Clinical Medical Research Center, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong, China. zou.chang@szhospital.com.
¹⁴ Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. margareta.pisarska@cshs.org.
¹⁵ California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA. hrtseng@mednet.ucla.edu.
¹⁶ California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA. yazhenzhu@mednet.ucla.edu.

^# Contributed equally.

Abstract

Placenta accreta spectrum (PAS) is a high-risk obstetrical condition associated with significant morbidity and mortality. Current clinical screening modalities for PAS are not always conclusive. Here, we report a nanostructure-embedded microchip that efficiently enriches both single and clustered circulating trophoblasts (cTBs) from maternal blood for detecting PAS. We discover a uniquely high prevalence of cTB-clusters in PAS and subsequently optimize the device to preserve the intactness of these clusters. Our feasibility study on the enumeration of cTBs and cTB-clusters from 168 pregnant women demonstrates excellent diagnostic performance for distinguishing PAS from non-PAS. A logistic regression model is constructed using a training cohort and then cross-validated and tested using an independent cohort. The combined cTB assay achieves an Area Under ROC Curve of 0.942 (throughout gestation) and 0.924 (early gestation) for distinguishing PAS from non-PAS. Our assay holds the potential to improve current diagnostic modalities for the early detection of PAS.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biomarkers / blood
Cell Aggregation
Cohort Studies
Diagnosis, Differential
Female
Humans
Lab-On-A-Chip Devices
Maternal Serum Screening Tests / instrumentation
Maternal Serum Screening Tests / methods*
Middle Aged
Nanostructures
Placenta Accreta / blood
Placenta Accreta / diagnosis*
Placenta Previa / blood
Placenta Previa / diagnosis
Pregnancy
ROC Curve
Reproducibility of Results
Trophoblasts / pathology*

Substances

Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding