The vascular stem cell niche: roadmap for transplanted neural progenitor cells during environmental enrichment?

Waldau, Ben

doi:10.4103/1673-5374.162692

Cited by 3 publications

(3 citation statements)

References 11 publications

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“…Similar observations have been made in graft survival studies in other disease models. 33 , 35 Lack of niche is less likely to affect implantation in the older mice, since they experienced a clear reduction in TM cell number at the beginning of the experiment.…”

Section: Discussionmentioning

confidence: 99%

Restoration of Aqueous Humor Outflow Following Transplantation of iPSC-Derived Trabecular Meshwork Cells in a Transgenic Mouse Model of Glaucoma

Zhu

Jain

Gramlich

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposePrimary open-angle glaucoma (POAG) is particularly common in older individuals and associated with pathologic degeneration of the trabecular meshwork (TM). We have shown previously that transplantation of induced pluripotent stem cell (iPSC) derived TM cells restores aqueous humor dynamics in young transgenic mice expressing a pathogenic form of human myocilin (Tg-MYOCY437H). This study was designed to determine if this approach is feasible in older mice with more pronounced TM dysfunction.MethodsMouse iPSC were differentiated toward a TM cell phenotype (iPSC-TM) and injected into the anterior chamber of 6-month-old Tg-MYOCY437H or control mice. IOP and aqueous humor outflow facility were recorded for up to 3 months. Transmission electron microscopy, Western blot, and immunohistochemistry were performed to analyze TM morphology, quantify endoplasmic reticulum (ER) stress, and assess TM cellularity.ResultsA 12 weeks after transplantation, IOP in iPSC-TM recipients was statistically lower and outflow facility was significantly improved compared to untreated controls. The number of endogenous TM cells increased significantly in iPSC-TM recipients along with the appearance of TM cells immmunopositive for a marker of cellular division. Morphologically, transplantation of iPSC-TM preserves ER structure 12 weeks after transplantation. However, myocilin and calnexin expression levels remain elevated in transplanted eyes of these 9-month-old Tg-MYOCY437H mice, indicating that ER stress persists within the TM.ConclusionsTransplantation of iPSC-TM can restore IOP and outflow facility in aged Tg-MYOCY437H mice. This type of stem cell–based therapy is a promising possibility for restoration of IOP control in some glaucoma patients.

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Section: Discussionmentioning

confidence: 99%

Restoration of Aqueous Humor Outflow Following Transplantation of iPSC-Derived Trabecular Meshwork Cells in a Transgenic Mouse Model of Glaucoma

Zhu

Jain

Gramlich

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Stem cell (SC) maintenance and function depend on signals from their local microenvironment, the SC niche. Adult neural, mesenchymal, and hematopoietic SCs neighbor the vasculature, which not only supplies oxygen and nutrients but also provides molecular signals to the stem cells (Goldberg and Hirschi, 2009; Gómez-Gaviro et al, 2012; Oh and Nör, 2015; Waldau, 2015), particularly through endothelial cells (Azevedo et al, 2017; Gao et al, 2018; Perlin et al, 2017). An intimate molecular communication from the vascular niche to the SCs contributes to tissue homeostasis and repair.…”

Section: Introductionmentioning

confidence: 99%

Skin vasculature and hair follicle cross-talking associated with stem cell activation and tissue homeostasis

Jain

et al. 2019

eLife

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Skin vasculature cross-talking with hair follicle stem cells (HFSCs) is poorly understood. Skin vasculature undergoes dramatic remodeling during adult mouse hair cycle. Specifically, a horizontal plexus under the secondary hair germ (HPuHG) transiently neighbors the HFSC activation zone during the quiescence phase (telogen). Increased density of HPuHG can be induced by reciprocal mutations in the epithelium (Runx1) and endothelium (Alk1) in adult mice, and is accompanied by prolonged HFSC quiescence and by delayed entry and progression into the hair growth phase (anagen). Suggestively, skin vasculature produces BMP4, a well-established HFSC quiescence-inducing factor, thus contributing to a proliferation-inhibitory environment near the HFSC. Conversely, the HFSC activator Runx1 regulates secreted proteins with previously demonstrated roles in vasculature remodeling. We suggest a working model in which coordinated remodeling and molecular cross-talking of the adult epithelial and endothelial skin compartments modulate timing of HFSC activation from quiescence for proper tissue homeostasis of adult skin.

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“…NSCs expanded derived from the fetal, postnatal and the adult brain, as well as ESCs and iPSCs, have therapeutic properties, which are evident from numerous studies employing grafting of NSCs into the aged brain and the adult brain afflicted with injury or disease. [4,36,42,43,45,94,96,101,109] The beneficial effects of NSC graft appear to be mainly mediated through enhancement of regeneration, plasticity and neurogenesis, and attenuation of neuroinflammation. [13,54,88] Indeed, several clinical trials are currently progressing in different phases.…”

Section: Introductionmentioning

confidence: 99%

Neural stem cell derived extracellular vesicles: Attributes and prospects for treating neurodegenerative disorders

2018

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Neural stem cell (NSC) grafting in conditions such as aging, brain injury, and neurodegenerative diseases promotes regeneration, plasticity and functional recovery. Recent studies have revealed that administration of NSC-derived extracellular vesicles (NSC-EVs) via non-invasive approaches can also afford therapeutic benefits. This review confers the properties and therapeutic promise of EVs secreted by NSCs. NSC-EVs enriched with specific miRNAs mediate multiple functions in physiological and pathological conditions, which include modulation of the proximate microenvironment, facilitating the entry of viruses into cells, functioning as independent metabolic units, operating as a microglial morphogen and influencing the diverse aspects of brain function in adulthood including the process of aging. Due to their anti-inflammatory, neurogenic and neurotrophic effects, NSC-EVs are also useful for treating multiple neurodegenerative diseases. Although only a few studies have demonstrated the efficacy of NSC-EVs to treat brain impairments, the promise is enormous. Moving forward, the use of well-characterized NSC-EVs generated in specific culture conditions and NSC-EVs that are engineered to carry the desired miRNAs, mRNAs and proteins have great promise for treating brain injury and neurogenerative diseases. Notably, the possibility of targeting NSC-EVs to specific neuronal types or brain regions would enable managing of diverse neurodegenerative conditions with minimal side effects.

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The vascular stem cell niche: roadmap for transplanted neural progenitor cells during environmental enrichment?

Cited by 3 publications

References 11 publications

Restoration of Aqueous Humor Outflow Following Transplantation of iPSC-Derived Trabecular Meshwork Cells in a Transgenic Mouse Model of Glaucoma

Restoration of Aqueous Humor Outflow Following Transplantation of iPSC-Derived Trabecular Meshwork Cells in a Transgenic Mouse Model of Glaucoma

Skin vasculature and hair follicle cross-talking associated with stem cell activation and tissue homeostasis

Neural stem cell derived extracellular vesicles: Attributes and prospects for treating neurodegenerative disorders

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