Umbilical cord-derived mesenchymal stromal cells: predictive obstetric factors for cell proliferation and chondrogenic differentiation

脐带间充质基质细胞:预测细胞增殖和软骨发生分化的产科因素

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作者:Léonore Avercenc-Léger, Philippe Guerci, Jean-Marc Virion, Ghislaine Cauchois, Sébastien Hupont, Rachid Rahouadj, Jacques Magdalou, Jean-François Stoltz, Danièle Bensoussan, Céline Huselstein, Loïc Reppel1

Background

The umbilical cord is becoming a notable alternative to bone marrow (BM) as a source of mesenchymal stromal cells (MSC). Although age-dependent variations in BM-MSC are well described, less data are available for MSC isolated from Wharton's jelly (WJ-MSC). We initiated a study to identify whether obstetric factors influenced MSC properties. We aimed to evaluate the correlation between a large number of obstetric factors collected during pregnancy and until peripartum (related to the mother, the labor and delivery, and the newborn) with WJ-MSC proliferation and chondrogenic differentiation parameters.

Conclusions

Awareness of obstetric factors influencing the proliferation and/or differentiation of WJ-MSC will make it possible to define criteria for collecting optimal umbilical cords with the aim of decreasing the variability of WJ-MSC batches produced for clinical use in cell and tissue engineering.

Methods

Correlations were made between 27 obstetric factors and 8 biological indicators including doubling time at passage (P)1 and P2, the percentage of proteoglycans and collagens, and the relative transcriptional expression of Sox-9, aggrecans, and total type 2 collagen (Coll2T).

Results

Amongst the obstetric factors considered, birth weight, the number of amenorrhea weeks, placental weight, normal pregnancy, and the absence of preeclampsia were identified as relevant factors for cell expansion, using multivariate linear regression analysis. Since all the above parameters are related to term, we concluded that WJ-MSC from healthy, full-term infants exhibit greater proliferation capacity. As for chondrogenesis, we also observed that obstetric factors influencing proliferation seemed beneficial, with no negative impact on MSC differentiation. Conclusions: Awareness of obstetric factors influencing the proliferation and/or differentiation of WJ-MSC will make it possible to define criteria for collecting optimal umbilical cords with the aim of decreasing the variability of WJ-MSC batches produced for clinical use in cell and tissue engineering.

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