Byron Oppliger1, Marianne S Joerger-Messerli1, Cedric Simillion2, Martin Mueller3, Daniel V Surbek1, Andreina Schoeberlein4. 1. Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Clinical Research, University of Bern, Switzerland. 2. Department of Clinical Research, University of Bern, Switzerland. 3. Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Clinical Research, University of Bern, Switzerland; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, Connecticut, USA. 4. Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Clinical Research, University of Bern, Switzerland. Electronic address: andreina.schoeberlein@dkf.unibe.ch.
Abstract
BACKGROUND AIMS: Wharton's jelly mesenchymal stromal cells (WJ-MSCs) might be ideal candidates to treat perinatal brain damage. Their secretome has been shown to have beneficial effects on neuroregeneration, in part through interaction with neural progenitor cells (NPCs). However, it remains unclear whether cell-to-cell contact decisively contributes to this positive effect. The objective of this study was to elucidate the mechanism through which differentiation in NPCs is triggered after exposure to WJ-MSCs. Furthermore, given that WJ-MSCs can be derived from term (tWJ-MSCs) or preterm (ptWJ-MSCs) deliveries and that WJ-MSCs might be used for transplantations independent of gestational age, the influence of tWJ-MSCs versus ptWJ-MSCs on the differentiation capacities of NPCs was studied. METHODS: The effect of tWJ-MSCs and ptWJ-MSCs on the expression of neuroglial markers in NPCs was assessed in co-culture (CC), conditioned medium (CM) or transwell CC experiments by immunocytochemistry, real-time polymerase chain reaction and Western blot. Additionally, mass spectrometry was used to study their secretomes. RESULTS: NPCs showed an increased expression of glial markers after CC with WJ-MSCs or exposure to WJ-MSC-CMs. CC had a more prominent effect on the expression of glial markers compared with CM or transwell CCs. tWJ-MSCs more strongly induced the expression of mature oligodendroglial markers compared with ptWJ-MSCs. A possible role in enhancing this maturation could be attributed to the laminin α2-subunit. CONCLUSIONS: Cell-to-cell contact between WJ-MSCs and NPCs induces oligodendrogenesis on NPCs, whereas trophic factor secretion is sufficient to promote astrogenesis. Thus, transplanting WJ-MSCs may promote endogenous neuroregeneration in perinatal brain damage.
BACKGROUND AIMS: Wharton's jelly mesenchymal stromal cells (WJ-MSCs) might be ideal candidates to treat perinatal brain damage. Their secretome has been shown to have beneficial effects on neuroregeneration, in part through interaction with neural progenitor cells (NPCs). However, it remains unclear whether cell-to-cell contact decisively contributes to this positive effect. The objective of this study was to elucidate the mechanism through which differentiation in NPCs is triggered after exposure to WJ-MSCs. Furthermore, given that WJ-MSCs can be derived from term (tWJ-MSCs) or preterm (ptWJ-MSCs) deliveries and that WJ-MSCs might be used for transplantations independent of gestational age, the influence of tWJ-MSCs versus ptWJ-MSCs on the differentiation capacities of NPCs was studied. METHODS: The effect of tWJ-MSCs and ptWJ-MSCs on the expression of neuroglial markers in NPCs was assessed in co-culture (CC), conditioned medium (CM) or transwell CC experiments by immunocytochemistry, real-time polymerase chain reaction and Western blot. Additionally, mass spectrometry was used to study their secretomes. RESULTS: NPCs showed an increased expression of glial markers after CC with WJ-MSCs or exposure to WJ-MSC-CMs. CC had a more prominent effect on the expression of glial markers compared with CM or transwell CCs. tWJ-MSCs more strongly induced the expression of mature oligodendroglial markers compared with ptWJ-MSCs. A possible role in enhancing this maturation could be attributed to the laminin α2-subunit. CONCLUSIONS: Cell-to-cell contact between WJ-MSCs and NPCs induces oligodendrogenesis on NPCs, whereas trophic factor secretion is sufficient to promote astrogenesis. Thus, transplanting WJ-MSCs may promote endogenous neuroregeneration in perinatal brain damage.
Authors: Narasimha M Beeraka; P R Hemanth Vikram; M V Greeshma; Chinnappa A Uthaiah; Tahani Huria; Junqi Liu; Pramod Kumar; Vladimir N Nikolenko; Kirill V Bulygin; Mikhail Y Sinelnikov; Olga Sukocheva; Ruitai Fan Journal: Mol Neurobiol Date: 2022-01-18 Impact factor: 5.590
Authors: Marianne S Joerger-Messerli; Gierin Thomi; Valérie Haesler; Irene Keller; Patricia Renz; Daniel V Surbek; Andreina Schoeberlein Journal: Front Cell Dev Biol Date: 2021-03-23