| Autor: |
Whitlock AE; Department of Surgery, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, USA., Moskowitzova K; Department of Surgery, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, USA., Kycia I; Department of Surgery, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, USA., Zurakowski D; Department of Surgery, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, USA., Fauza DO; Department of Surgery, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, USA. |
| Jazyk: |
angličtina |
| Zdroj: |
Stem cells and development [Stem Cells Dev] 2023 Aug; Vol. 32 (15-16), pp. 484-490. |
| DOI: |
10.1089/scd.2023.0040 |
| Abstrakt: |
Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can attenuate placental inflammation and minimize intrauterine growth restriction (IUGR). We sought to determine whether MSC-based TRASCET could mitigate fetal cardiopulmonary effects of IUGR. Pregnant Sprague-Dawley dams were exposed to alternating 12-h hypoxia (10.5% O 2 ) cycles in the last fourth of gestation. Their fetuses ( n = 155) were divided into 4 groups. One group remained untreated ( n = 42), while three groups received volume-matched intra-amniotic injections of either saline (sham; n = 34), or of syngeneic amniotic fluid-derived MSCs, either in their native state (TRASCET; n = 36) or "primed" by exposure to interferon-gamma and interleukin-1beta before administration in vivo (TRASCET-primed; n = 43). Normal fetuses served as additional controls ( n = 30). Multiple morphometric and biochemical analyses were performed at term for select markers of cardiopulmonary development and inflammation previously shown to be affected by IUGR. Among survivors (75%; 117/155), fetal heart-to-body weight ratio was increased in both the sham and untreated groups ( P < 0.001 for both) but normalized in the TRASCET and TRASCET-primed groups ( P = 0.275, 0.069, respectively). Cardiac b-type natriuretic peptide levels were increased in all hypoxia groups compared with normal ( P < 0.001), but significantly decreased from sham and untreated in both TRASCET groups ( P < 0.0001-0.005). Heart tumor necrosis factor-alpha levels were significantly elevated in sham and TRASCET groups ( P = 0.009, 0.002), but normalized in the untreated and TRASCET-primed groups ( P = 0.256, 0.456). Lung transforming growth factor-beta levels were significantly increased in both sham and untreated groups ( P < 0.001, 0.003), but normalized in both TRASCET groups ( P = 0.567, 0.303). Similarly, lung endothelin-1 levels were elevated in sham and untreated groups ( P < 0.001 for both), but normalized in both TRASCET groups ( P = 0.367, 0.928). We conclude that TRASCET with MSCs decreases markers of fetal cardiac strain, insufficiency, and inflammation, as well as of pulmonary fibrosis and hypertension in the rodent model of IUGR. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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