A promising source of MSCs for therapeutic uses is Wharton’s Jelly. WJ-MSCs are easily accessible with many advantages over the BM-MSCs. Several maternal and neonatal parameters have been studied in relation to the characterization and quality of hematopoietic UC blood stem cells in the past. Although research on how maternal and neonatal variables affect the yield of WJ-MSCs is still under research investigation. For the purpose of aiding in finding and selecting the ideal UC donors, this study studied the effects of many maternal and fetal factors on the yield of WJ-MSCs.
According to our findings, the mother’s age has a substantial impact on the yield of WJ-MSCs. This is in agreement with the findings of22, who found that whereas UC-MSCs from elder donors show diminished differentiation potential, UC from younger donors is a reasonably abundant source of MSCs. Furthermore, compared to younger age groups, there was a significant negative correlation in the expression levels of both CD29 and CD105, according to23. It was reported that as a woman ages increase, her mesenchymal stem cells expressing the BIRC2 and BIRC3 genes decrease as stem cells obtained from younger women may exhibit more apoptotic resistance and a more stem cell-like quality, which may enhance their therapeutic potential and clinical usability16.
A known pluripotent transcription factor, SOX2 is implicated in reprogramming, self-renewal, and maintaining the homeostasis of stem cells. The SOX2 gene is statistically considerably more expressed in WJSC in women under the age of 34 than it is in women over 34, according to24. Furthermore, a statistically significant moderate negative correlation is demonstrated between the SOX2 gene expression and the maternal age. This result was clarified by25 and26, who found that aging in mothers is related to telomere shortening and increased susceptibility to apoptosis, and that stem cells’ telomere length could not be maintained by the level of telomerase activity.
These results largely stated the decline in CD105, CD73, and CD90 expression levels that they reported in their study’s UC-MSCs as they were older. Furthermore, it has been previously reported how aging affects adult stem cells27 found a decrease in adult MSCs number derived from the bone marrow with aging. According to28, there is a decrease in the quantity, functionality, and multi-lineage differentiation characteristics of mature MSCs as they age. Additionally, the authors hypothesized that the lower differentiation capacity of the older donor’s umbilical cord cells could be related to the declining functional state of the mother’s older organs, which support and foster the development of umbilical cord MSC22. Conversely to this finding, maternal age had no effect on the quality of WJ-MSCs, according to29.
As per the study carried out by30, vaginal and cesarean births had MSC cell yields that were comparable. According to Penolazzi et al.29, the method of delivery had no impact on the characteristics or survivability of MSCs. To reduce the incidence of contamination, we only used specimens from Cesarean births in our investigation. We observed that the WJ-MSCs count and doubling time were not more impacted by birth order. A reduction in the number of WJ-MSCs was correlated with increasing parity, nevertheless the relationship was not statistically significant. Birth order and viability showed a moderately positive association (r = 0.119, P = 0.044), whereas parity and the amount of UC blood showed no correlation (P = 0.057)31. According to32, WJ-MSCs obtained from younger women who gave vaginal delivery have increased expression of the BIRC2, BIRC3, and BIRC5 genes.
Pre-eclampsia had no obvious effect on the population doubling time or WJ-MSC yield in this study. In contrast, pre-eclampsia has been shown by33 to result in a considerable increase in cell count and reduction in the fraction of immature cells and increasing the mature cells. Compared to normal samples, the proliferation rate of early-passage gestational diabetes mellitus (DM) samples was significantly lower34 . Furthermore, with a mean cell density of 1.9 × 104 cells per plate in gestational DM samples as opposed to 4.1 × 104 cells per plate in normal samples, the population doubling rate was considerably lower in these samples after 12 days of incubation. Gestational DM-UC-MSCs did not grow above passages 6 or 7. All UC-MSCs had comparable amounts of the stem cell markers CD90, CD73, and CD105 during early stages. These results are consistent with a study conducted by35, which found that MSCs derived from Wharton Jelly of the DM group grew and proliferated at a much slower rate in all passages than MSCs isolated from a control group. The quantity of non-viable cells in the gestational DM samples significantly increased than viable cells.
The WJ-MSCs count was shown to be statistically significantly impacted by gestational age in our investigation, although there was not a significant association established between gestational age and P1 doubling time. Nevertheless, there was no statistically significant difference in the median MSC output between full-term and preterm newborn when comparing them to full-term babies. Fourty five infants were divided into three groups in a study conducted by36 according to their gestational ages: group A (28–31 weeks), group B (32–35 weeks), and group (C) ≥ 36 weeks. Even after adjusting the birth weight, maternal co-morbidities, and prenatal steroid use, the authors still found a significant inverse correlation between gestational age and MSC yield. Similar findings were reported by37, who found that despite both samples maintained a high rate of proliferation, preterm cord samples developed more MSC in all passages than term cords. On the other hand, according to38, the quantity of umbilical cord vein UC-MSCs from both full term and preterm patients is comparable, and both groups exhibit a high rate of proliferation. Penolazzi et al.29, on the other hand, found no correlation between gestational age and MSC yield.
Age at gestation may possibly have an impact on the UC-MSCs’ potential to modulate immunity. According to38, preterm UC-MSCs do not have the same potent inhibitory effects on immune cell proliferation as full-term UC-MSCs. A lymphocyte co-culture experiment revealed that both full term and preterm UC-MSCs reduced peripheral blood mononuclear cell proliferation in the mixed lymphocyte response. Compared to preterm UC-MSCs, the term UC-MSCs had a stronger proliferation inhibition. The scientists explained the inhibitory difference by the preterm UC-MSCs’ immature immune systems. The source, donor age, and passage number of cells can also have an impact on the immuno-modulatory qualities of MSCs39 and40.
According to41, placental weight, birth weight, and full term birth were the primary factors influencing cell proliferation. Despite the strong correlation between these parameters and gestational age, multivariate regression analysis revealed that gestational age was the only independent predictor of population doubling time (P = 0.0094). Our study found that the baby’s birth weight had a substantial impact on the number of WJ-MSCs; a greater birth weight leads to increased the yield of MSCs. According to30, the yield of MSCs was not significantly affected by the mother’s age or gestational age, but a greater birth weight was associated with a more yield, which is consistent with our findings. On the other hand, Gil-Kulik et al.24 found that lower birth weight correlates to higher SOX2 gene expression in WJ-SCs. SOX2 is a known pluripotent transcription factor that contributes to cell reprogramming and self-renewal. According to Penolazzi et al.29, the MSCs output was not significantly impacted by birth weight. The author explained that their study focused on the quality of the stem cells not the number so the study finding differs from other studies that correlate the number of isolated stem cells to the birth weight31,42.
According to our findings, there was no statistically significant difference in the WJ-MSCs yields in regard to fetal gender, presentation, length at birth, or head circumference. According to36, the mean MSCs number of female neonates was greater than that of male infants. When comparing MSCs separated from WJ from female individuals to MSCs obtained from WJ from male subjects, Balzano et al.43 observed that the expression of OCT4 and DNMT1 genes was considerably greater in WJ-MSCs derived from male participants. They came to the conclusion that gender significantly affects stemness genes. However,29 found that gender did not affect the quality of WJ-MSCs.
We discovered a statistically significant negative association between doubling time and UC width and a slight positive correlation between MSCs yield and UC width.
We discovered that the amount of meconium in the amniotic fluid had no effect on the production of MSCs or the population doubling time. According to44, there was little change in the expression of the mesenchymal markers CD90 and CD105 following exposure to meconium. Amniotic fluid MSCs may change in phenotype after being exposed to meconium, although they are still capable of differentiating.
To sum up, Wharton’s jelly MSCs are a perfect and exciting source of MSCs. Numerous factors related to mothers and newborns may impact the MSC output and should be investigated for settling the optimal selection criteria for the ideal donors. Our research showed that a higher yield of MSCs produced from Wharton’s jelly correlates to a younger mother’s age, increased birth weight, and longer gestational age.
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- Source: https://www.nature.com/articles/s41598-024-72386-z