Juxtacrine signalling via Notch and ErbB receptors in the switch to fate commitment of bone marrow‐derived Schwann cells

Shea, Graham Ka‐Hon; Tai, Evelyn Wing-Ying; Leung, Katherine Ho‐Yan; Mung, Kwan Long; Li, Maximilian Tak-Sui; Tsui, Alex Y.P.; Tam, Anthony; Shum, Dky; Chan, Yuen-Yan

doi:10.1111/ejn.14837

Cited by 4 publications

(11 citation statements)

References 42 publications

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“…We extracted and expanded aMSCs as reported previously [16][17][18][19][20][21]. Primary aM-SCs (passages 3-8) were fibroblastic in morphology (Figure 1A) and proliferated steadily throughout passage 4 to 8.…”

Section: Characterization Of Primary and Cryopreserved Amscsmentioning

confidence: 86%

“…aMSCs were cultured and characterized according to our previous publications [16][17][18][19][20][21] with modifications. Briefly, young adult rats were euthanized with anesthetic overdose (pentobarbital 150 mg/kg i.p., Alfasan, Utrecht, The Netherlands).…”

Section: Bone Marrow Extraction Amsc Culture and Cryopreservationmentioning

confidence: 99%

“…Neuroprogenitor cells were selectively expanded using non-adherent culture [16][17][18][19][20][21]. Briefly, aMSCs were seeded at 10,000 cells/cm 2 density onto Ultra Low ® non-adherent 6-well plates (Corning, Corning, NY, USA) in sphere-forming medium (SFM) comprising DMEM/F12 (Thermo Fisher Scientific) supplemented with 2% B27 (Thermo Fisher Scientific), bFGF, and EGF (20 ng/mL, Peprotech, Rehovot, Israel).…”

Section: Neural Progenitor Derivationmentioning

confidence: 99%

“…Dorsal root ganglia of embryonic day 15 rats were dissociated with TrypLE Express and collected by centrifugation (250× g, 5 min, 4 • C) [16][17][18][19][20][21]. Cells were resuspended in neuron maintenance medium comprising Neurobasal medium (Thermo Fisher Scientific) supplemented with 2% B27 and NGF (20 ng/mL, Millipore, Burlington, MA, USA) and then seeded at 100,000 cells/cm 2 onto poly-D-lysine/laminin-coated plates.…”

Section: Amsc-derived Op-neuron Co-culturementioning

confidence: 99%

“…Derivation of myelin-forming Schwann cells from adult bone marrow stromal cells (aMSCs) showed that neural progenitors were harbored in aMSCs [16][17][18][19][20][21]. We hypothe-sized that these neural progenitors could be expanded and differentiated into OPs, without genetic manipulation.…”

Section: Introductionmentioning

confidence: 99%

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Derivation of Oligodendrocyte Precursors from Adult Bone Marrow Stromal Cells for Remyelination Therapy

Tsui

Lam

et al. 2021

Cells

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Transplantation of oligodendrocyte precursors (OPs) is potentially therapeutic for myelin disorders but a safe and accessible cell source remains to be identified. Here we report a two-step protocol for derivation of highly enriched populations of OPs from bone marrow stromal cells of young adult rats (aMSCs). Neural progenitors among the aMSCs were expanded in non-adherent sphere-forming cultures and subsequently directed along the OP lineage with the use of glial-inducing growth factors. Immunocytochemical and flow cytometric analyses of these cells confirmed OP-like expression of Olig2, PDGFRα, NG2, and Sox10. OPs so derived formed compact myelin both in vitro, as in co-culture with purified neurons, and in vivo, following transplantation into the corpus callosum of neonatal shiverer mice. Not only did the density of myelinated axons in the corpus callosum of recipient shiverer mice reach levels comparable to those in age-matched wild-type mice, but the mean lifespan of recipient shiverer mice also far exceeded those of non-recipient shiverer mice. Our results thus promise progress in harnessing the OP-generating potential of aMSCs towards cell therapy for myelin disorders.

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Section: Characterization Of Primary and Cryopreserved Amscsmentioning

confidence: 86%

Section: Bone Marrow Extraction Amsc Culture and Cryopreservationmentioning

confidence: 99%

Section: Neural Progenitor Derivationmentioning

confidence: 99%

Section: Amsc-derived Op-neuron Co-culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Derivation of Oligodendrocyte Precursors from Adult Bone Marrow Stromal Cells for Remyelination Therapy

Tsui

Lam

et al. 2021

Cells

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Prospects of cell replacement therapy for the treatment of degenerative cervical myelopathy

Shea

Koljonen

Chan

2020

Reviews in the Neurosciences

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Degenerative cervical myelopathy (DCM) presents insidiously during middle-age with deterioration in neurological function. It accounts for the most common cause of non-traumatic spinal cord injury in developed countries and disease prevalence is expected to rise with the aging population. Whilst surgery can prevent further deterioration, biological therapies may be required to restore neurological function in advanced disease. Cell replacement therapy has been inordinately focused on treatment of traumatic spinal cord injury yet holds immense promise in DCM. We build upon this thesis by reviewing the pathophysiology of DCM as revealed by cadaveric and molecular studies. Loss of oligodendrocytes and neurons occurs via apoptosis. The tissue microenvironment in DCM prior to end-stage disease is distinct from that following acute trauma, and in many ways more favourable to receiving exogenous cells. We highlight clinical considerations for cell replacement in DCM such as selection of cell type, timing and method of delivery, as well as biological treatment adjuncts. Critically, disease models often fail to mimic features of human pathology. We discuss directions for translational research towards clinical application.

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The interplay of common genetic variants NRG1 rs2439302 and RET rs2435357 increases the risk of developing Hirschsprung’s disease

Chi,

Li,

Cao

et al. 2023

Front. Cell Dev. Biol.

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Introduction: As a congenital and genetically related disease, many single nucleotide polymorphisms (SNPs) have been reported to be associated with the risk of HSCR. Our previous research showed that SNP rs2439302 (NRG1) interacted with rs2435357 (RET) to increase the risk of HSCR development. However, the underlying molecular mechanism is still not well understood.Methods: SNP rs2439302 (NRG1) and rs2435357 (RET) were genotyped in 470 HSCR cases. The expression of NRG1 and RET was investigated in the colon of HSCR patients. Knockdown of the NRG1 and RET homologs was performed in zebrafish to investigate their synergistic effect on ENS development. The effect of SNP rs2439302 and rs2435357 polymorphism on neuron proliferation, migration, and differentiation were investigated in SHSY-5Y cells and IPSCs.Results: Significant downregulation of NRG1 and RET expression was noticed in the aganglionic segment of HSCR patients and SHSY-5Y cells with rs2439302 GG/rs2435357 TT genotype. NRG1 and RET double mutants caused the most severe reduction in enteric neuron numbers than NRG1 single mutant or RET single mutant in the hindgut of zebrafish. SHSY-5Y cells and IPSCs with rs2439302 GG/rs2435357 TT genotype exhibited a decreased proliferative, migration, and differentiative capacity. CTCF showed a considerably higher binding ability to SNP rs2439302 CC than GG. NRG1 reduction caused a further decrease in SOX10 expression via the PI3K/Akt pathway, which regulates RET expression by directly binding to rs2435357.Discussion: SNP rs2439302 (NRG1) GG increases the risk of developing HSCR by affecting the binding of transcription factor CTCF and interacting with rs2435357 (RET) to regulate RET expression via the PI3K/Akt/SOX10 pathway.

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Juxtacrine signalling via Notch and ErbB receptors in the switch to fate commitment of bone marrow‐derived Schwann cells

Cited by 4 publications

References 42 publications

Derivation of Oligodendrocyte Precursors from Adult Bone Marrow Stromal Cells for Remyelination Therapy

Derivation of Oligodendrocyte Precursors from Adult Bone Marrow Stromal Cells for Remyelination Therapy

Prospects of cell replacement therapy for the treatment of degenerative cervical myelopathy

The interplay of common genetic variants NRG1 rs2439302 and RET rs2435357 increases the risk of developing Hirschsprung’s disease

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