Human cord blood hematopoietic cells acquire neural features when cultured in the presence of neurogenic cytokines.

In vitro growth of hematopoietic cells depends on the presence of hematopoietic cytokines. To date, it is unclear if these cells would be able to respond to non-hematopoietic cytokines. In the present study, we have explored this by culturing human hematopoietic cells in presence of neurogenic cytokines. Lineage-negative (Lin-) umbilical cord blood (UCB)-derived cells -enriched for hematopoietic stem and progenitor cells- were cultured in presence of different combinations of hematopoietic cytokines, neurotrophins, epidermal growth factor, fibroblast growth factor, and neurogenic culture media, in a 3-phase culture system. A proportion (1-22%) of Lin- UCB hematopoietic cells normally express neural markers and are capable of responding to neural cytokines. Neural cytokines did not have effects on hematopoietic cell proliferation; however, we observed generation of neural-like cells, assessed by morphology, and a significant increase in the proportion of cells expressing neural markers. Such neural-like cells, however, retained expression of hematopoietic markers. It seems that under our culture conditions, no actual transdifferentiation of hematopoietic cells into neural cells occurred; instead, the cells generated in culture seem to be hematopoietic cells that acquired neural features upon contact with neurogenic factors. The identity of UCB cells that acquired a neural phenotype is still unclear.

Functional Integrity and Gene Expression Profiles of Human Cord Blood-Derived Hematopoietic Stem and Progenitor Cells Generated In Vitro.

To date, different experimental strategies have been developed for the ex vivo expansion of human hematopoietic stem (HSCs) and progenitor (HPCs) cells. This has resulted in significant advances on the use of such expanded cells in transplantation settings. To this day, however, it is still unclear to what extent those stem and progenitor cells generated in vitro retain the functional and genomic integrity of their freshly isolated counterparts. In trying to contribute to the solving of this issue, in the present study we have selected and purified three different hematopoietic cell populations: HSCs (CD34+ CD38- CD45RA- CD71- Lin- cells), myeloid progenitor cells (CD34+ CD38+ CD45RA+ CD71- Lin- cells), and erythroid progenitor cells (CD34+ CD38+ CD45RA- CD71+ Lin- cells), obtained directly from fresh human umbilical cord blood (UCB) units or generated in vitro under particular culture conditions. We, then, compared their functional integrity in vitro and their gene expression profiles. Our results indicate that in spite of being immunophenotipically similar, fresh and in vitro generated cells showed significant differences, both in functional and genetic terms. As compared to their fresh counterparts, those HSCs generated in our culture system showed a deficient content of long-term culture-initiating cells, and a marked differentiation bias toward the myeloid lineage. In addition, in vitro generated HSCs and HPCs showed a limited expansion potential. Such functional alterations correlated with differences in their gene expression profiles. These observations are relevant in terms of HSC biology and may have implications in UCB expansion and transplantation. Stem Cells Translational Medicine 2018;7:602-614.

Protein malnutrition and aging affects entraining and intensity of locomotor activity and body temperature circadian rhythms in rats.

Independently, chronic protein malnutrition and aging have been shown to affect locomotor activity (LA) and body temperature (BT) rhythms in mammals. The objective of the present study was to ascertain the combined effects of these two factors by examining period, entrainment and other circadian parameters between LA and BT rhythms. Chronic protein malnourished (PM) and well-nourished (WN) male Sprague-Dawley rats (550-590 days of age) were implanted with activity temperature intraperitoneal radio transmitters (Mini Mitter) and exposed to different lighting protocols during at least 10 days - light-dark cycles (LD 12:12), constant darkness (DD), skeleton photoperiod (SP) and again LD. Results indicate that parametric entrainment, achieved by means of complete photoperiod, is not negatively affected in malnourished rats; however, it is affected under non-parametric entrainment like SP. A different free running period between the LA and BT circadian rhythms was detected for well-nourished and malnourished aged rats.