# Human umbilical mesenchymal stem cell-derived mitochondria transplantation suppresses sFLT-1 secretion by regulating calcineurin-NFAT-dependent pathways in angiotensin II-induced preeclampsia rats

## TL;DR

Human umbilical stem cell mitochondria help treat preeclampsia in rats by reducing harmful protein levels and improving placental function.

## Contribution

This study shows that mitochondrial transplantation from human umbilical stem cells can reverse preeclampsia symptoms in rats.

## Key findings

- Mito-T reduced sFLT-1 levels and improved placental mitochondrial function in preeclampsia rats.
- Mito-T increased mitochondrial fusion proteins and decreased fission/mitophagy proteins in placental tissue.
- Mito-T suppressed calcineurin-NFAT pathways in trophoblast cells and placental tissue.

## Abstract

Mitochondrial transplantation (Mito-T) is a novel therapeutic strategy for ischaemic cardiovascular diseases. This study aimed to test the efficacy of human umbilical mesenchymal stem cell-derived mitochondrial transplantation (Mito-T) on preeclampsia (PE).

PE was induced in Sprague–Dawley pregnant rats by infusing angiotensin II (Ang II) starting on gestation day 8 (GD 8). Mito-T (100 μg/μl) was injected via the jugular vein on GD 14.

On GD 20, PE rats exhibited high blood pressure, kidney and placental vascular abnormalities, reduced placental and foetal weights, foetal crown-rump lengths. Mito-T was predominantly distributed in the kidneys, uterus, and placenta of PE rats. Mito-T reversed clinical manifestations of PE, restored placental vascular abnormalities, and reduced serum sFLT-1 levels and the sFLT-1/PlGF ratio. In placental mitochondria, Mito-T increased protein levels of complexes (I‒V), improved mitochondrial membrane potential, ATP synthase, citrate synthase activities, and biogenesis markers (PGC-1α, TFAM, and NRF1), and reduced reactive oxygen species production. Mito-T increased mitochondrial fusion proteins (OPA1, MFN1, and MFN2) in the placenta, whereas fission (DRP1 and FIS1) and mitophagy (PINK, BNIP3, BNIP3L, and FUNDC1) proteins were reduced. In placental tissue, primary trophoblast cells, and the Bewo cell line, Mito-T reduced the mRNA and protein levels of sFLT-1 and attenuated the calcineurin-NFAT pathways elevated by PE or Ang II.

This study demonstrates that Mito-T reverses the pathological phenotypes of PE rats by improving placental mitochondrial activity and suppressing trophoblast-derived sFLT-1 production. These findings provide proof-of-concept evidence that Mito-T could serve as a potential therapeutic strategy for reducing maternal and foetal risks in patients with PE.

The online version contains supplementary material available at 10.1186/s13287-026-04930-9.