76 research outputs found
Runt-Related Transcription Factor 2 Induction During Differentiation of Wharton's Jelly Mesenchymal Stem Cells to Osteoblasts Is Regulated by Jumonji AT-Rich Interactive Domain 1B Histone Demethylase
Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of Wharton Jelly mesenchymal stem cells secretome?
Introduction: The use of human umbilical cord Wharton Jelly-derived mesenchymal stem cells (hWJ-MSCs) has been considered a new potential source for future safe applications in regenerative medicine. Indeed, the application of hWJ-MSCs into different animal models of disease, including those from the central nervous system, has shown remarkable therapeutic benefits mostly associated with their secretome. Conventionally, hWJ-MSCs are cultured and characterized under normoxic conditions (21 % oxygen tension), although the oxygen levels within tissues are typically much lower (hypoxic) than these standard culture conditions. Therefore, oxygen tension represents an important environmental factor that may affect the performance of mesenchymal stem cells in vivo. However, the impact of hypoxic conditions on distinct mesenchymal stem cell characteristics, such as the secretome, still remains unclear. Methods: In the present study, we have examined the effects of normoxic (21 % O2) and hypoxic (5 % O2) conditions on the hWJ-MSC secretome. Subsequently, we address the impact of the distinct secretome in the neuronal cell survival and differentiation of human neural progenitor cells. Results: The present data indicate that the hWJ-MSC secretome collected from normoxic and hypoxic conditions displayed similar effects in supporting neuronal differentiation of human neural progenitor cells in vitro. However, proteomic analysis revealed that the use of hypoxic preconditioning led to the upregulation of several proteins within the hWJ-MSC secretome. Conclusions: Our results suggest that the optimization of parameters such as hypoxia may lead to the development of strategies that enhance the therapeutic effects of the secretome for future regenerative medicine studies and applications. © 2015 Teixeira et al.Portuguese Foundation for Science and Technology (FCT) (Ciência 2007
program and IF Development Grant (AJS); and pre-doctoral fellowships to
FGT (SFRH/69637/ 2010) and SIA (SFRH/BD/81495/2011); Canada Research
Chairs (LAB) and a SSE Postdoctoral Fellowship (KMP); The National Mass
Spectrometry Network (RNEM) (REDE/1506/REM/2005); co-funded by Programa
Operacional Regional do Norte (ON.2 – O Novo Norte), ao abrigo do Quadro de
Referência Estratégico Nacional (QREN), através do Fundo Europeu de
Desenvolvimento Regional (FEDER).info:eu-repo/semantics/publishedVersio
Intracoronary infusion of Wharton’s jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial
Transplantation of human Wharton’s jelly-derived mesenchymal stem cells highly expressing TGFβ receptors in a rabbit model of disc degeneration
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A Combinatorial Approach to Promote Regeneration after Spinal Cord injury via Biomaterials, Neural stem cells, and Immunomodulation
Spinal cord injury (SCI) disrupts the blood-spinal cord barrier, allowing immune cells to infiltrate spinal cord tissue and further exacerbating the injury. This causes CNS cell death, axonal dieback, demyelination, and build-up of inhibitory factors that limit axonal and myelin regeneration. Several decades of extensive SCI research have made it clear that this complex problem requires combinatorial solutions. This dissertation investigates three therapeutic approaches for SCI: (A) implantation of multi-channel poly (lactide-co-glycolide) (PLG) biomaterial that can bridge the defect and guide axonal growth through inhibitory barriers; (B) human Neural Stem Cell (hNSC) transplantation to replenish lost CNS cells and to myelinate regenerating axons; and (C) expression of anti-inflammatory cytokines like interleukin-10 (IL-10) to modulate the SCI inflammatory milieu and offer neuroprotection. The first chapter introduces the conceptual background for these studies. The second chapter investigates the combination of acute PLG bridge implantation and chronic hNSC transplantation for SCI. Highlights of this chapter include enhancement of hNSC engraftment, hNSC migration along regenerated axons growing into the bridge, hNSC differentiation into oligodendrocytes and myelinating host axons, hNSC-derived neurons integrating into mouse neural circuitry, and improvement in motor recovery. Additionally, I show novel evidence supporting the formation of a synaptic circuit connecting corticospinal neurons in the motor cortex and the forelimb neuromuscular junction via the PLG bridge. This study highlights the significance of a guided bridge conduit in the injury site to reestablish lost connections and hNSC transplantation to myelinate the spared and regenerated circuitry and unleash the full potential of hNSC-based regenerative therapies. The third chapter investigates the effect of localized lentiviral expression of IL-10 with or without PLG bridge implantation on outcomes after spinal cord injury. Highlights of this chapter include: IL-10 modulates the inflammatory microenvironment and significantly enhances regeneration and myelination in the PLG bridge, and this combined approach resulted in a synergistic improvement in motor recovery. Additionally, using transsynaptic PRV tracing, I demonstrate the bridge supports the rewiring of spinal neuronal circuitry from the motor cortex and PVN of the hypothalamus and further enhancement in PVN circuitry with IL-10 delivery
Phenotypic and functional comparison of optimum culture conditions for upscaling of dental pulp stem cells
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Induction of early neural precursors and derivation of tripotent neural stem cells from human pluripotent stem cells under xeno-free conditions.
Human embryonic stem cells (hESC) and induced pluripotent stem cells (hiPSC) can differentiate into many cell types and are important for regenerative medicine; however, further work is needed to reliably differentiate hESC and hiPSC into neural-restricted multipotent derivatives or specialized cell types under conditions that are free from animal products. Toward this goal, we tested the transition of hESC and hiPSC lines onto xeno-free (XF) / feeder-free conditions and evaluated XF substrate preference, pluripotency, and karyotype. Critically, XF transitioned H9 hESC, Shef4 hESC, and iPS6-9 retained pluripotency (Oct-4 and NANOG), proliferation (MKI67 and PCNA), and normal karyotype. Subsequently, XF transitioned hESC and hiPSC were induced with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) to generate neuralized spheres containing primitive neural precursors, which could differentiate into astrocytes and neurons, but not oligoprogenitors. Further neuralization of spheres via LIF supplementation and attachment selection on CELLstart substrate generated adherent human neural stem cells (hNSC) with normal karyotype and high proliferation potential under XF conditions. Interestingly, adherent hNSC derived from H9, Shef4, and iPS6-9 differentiated into significant numbers of O4+ oligoprogenitors (∼20-30%) with robust proliferation; however, very few GalC+ cells were observed (∼2-4%), indicative of early oligodendrocytic lineage commitment. Overall, these data demonstrate the transition of multiple hESC and hiPSC lines onto XF substrate and media conditions, and a reproducible neuralization method that generated neural derivatives with multipotent cell fate potential and normal karyotype
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