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Nakagomi T, Nakano-Doi A, Kubo S, Sawano T, Kuramoto Y, Yamahara K, Matsuyama T, Takagi T, Doe N, Yoshimura S. Transplantation of Human Brain-Derived Ischemia-Induced Multipotent Stem Cells Ameliorates Neurological Dysfunction in Mice After Stroke. Stem Cells Transl Med 2023:7177376. [PMID: 37221140 DOI: 10.1093/stcltm/szad031] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 04/20/2023] [Indexed: 05/25/2023] Open
Abstract
We recently demonstrated that injury/ischemia-induced multipotent stem cells (iSCs) develop within post-stroke human brains. Because iSCs are stem cells induced under pathological conditions, such as ischemic stroke, the use of human brain-derived iSCs (h-iSCs) may represent a novel therapy for stroke patients. We performed a preclinical study by transplanting h-iSCs transcranially into post-stroke mouse brains 6 weeks after middle cerebral artery occlusion (MCAO). Compared with PBS-treated controls, h-iSC transplantation significantly improved neurological function. To identify the underlying mechanism, green fluorescent protein (GFP)-labeled h-iSCs were transplanted into post-stroke mouse brains. Immunohistochemistry revealed that GFP+ h-iSCs survived around the ischemic areas and some differentiated into mature neuronal cells. To determine the effect on endogenous neural stem/progenitor cells (NSPCs) by h-iSC transplantation, mCherry-labeled h-iSCs were administered to Nestin-GFP transgenic mice which were subjected to MCAO. As a result, many GFP+ NSPCs were observed around the injured sites compared with controls, indicating that mCherry+ h-iSCs activate GFP+ endogenous NSPCs. In support of these findings, coculture studies revealed that the presence of h-iSCs promotes the proliferation of endogenous NSPCs and increases neurogenesis. In addition, coculture experiments indicated neuronal network formation between h-iSC- and NSPC-derived neurons. These results suggest that h-iSCs exert positive effects on neural regeneration through not only neural replacement by grafted cells but also neurogenesis by activated endogenous NSPCs. Thus, h-iSCs have the potential to be a novel source of cell therapy for stroke patients.
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Affiliation(s)
- Takayuki Nakagomi
- Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan
- Department of Therapeutic Progress in Brain Diseases, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan
| | - Akiko Nakano-Doi
- Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan
- Department of Therapeutic Progress in Brain Diseases, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan
| | - Shuji Kubo
- Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan
| | - Toshinori Sawano
- Department of Biomedical Sciences, Ritsumeikan University, Kusatsu, Japan
| | - Yoji Kuramoto
- Department of Neurosurgery, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan
| | - Kenichi Yamahara
- Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan
| | - Tomohiro Matsuyama
- Department of Therapeutic Progress in Brain Diseases, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan
| | - Toshinori Takagi
- Department of Neurosurgery, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan
| | - Nobutaka Doe
- Department of Rehabilitation, Hyogo Medical University (Kobe Campus), Chuo-ku, Kobe, Hyogo, Japan
| | - Shinichi Yoshimura
- Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan
- Department of Neurosurgery, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan
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Ott LC, Han CY, Mueller JL, Rahman AA, Hotta R, Goldstein AM, Stavely R. Bone Marrow Stem Cells Derived from Nerves Have Neurogenic Properties and Potential Utility for Regenerative Therapy. Int J Mol Sci 2023; 24:5211. [PMID: 36982286 PMCID: PMC10048809 DOI: 10.3390/ijms24065211] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 03/02/2023] [Accepted: 03/06/2023] [Indexed: 03/12/2023] Open
Abstract
Neurons and glia of the peripheral nervous system are derived from progenitor cell populations, originating from embryonic neural crest. The neural crest and vasculature are intimately associated during embryonic development and in the mature central nervous system, in which they form a neurovascular unit comprised of neurons, glia, pericytes, and vascular endothelial cells that play important roles in health and disease. Our group and others have previously reported that postnatal populations of stem cells originating from glia or Schwann cells possess neural stem cell qualities, including rapid proliferation and differentiation into mature glia and neurons. Bone marrow receives sensory and sympathetic innervation from the peripheral nervous system and is known to contain myelinating and unmyelinating Schwann cells. Herein, we describe a population of neural crest-derived Schwann cells residing in a neurovascular niche of bone marrow in association with nerve fibers. These Schwann cells can be isolated and expanded. They demonstrate plasticity in vitro, generating neural stem cells that exhibit neurogenic potential and form neural networks within the enteric nervous system in vivo following transplantation to the intestine. These cells represent a novel source of autologous neural stem cells for the treatment of neurointestinal disorders.
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Affiliation(s)
| | | | | | | | | | - Allan M. Goldstein
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Rhian Stavely
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
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Jaloux C, Bonnet M, Vogtensperger M, Witters M, Veran J, Giraudo L, Sabatier F, Michel J, Legré R, Guiraudie-Capraz G, Féron F. Human nasal olfactory stem cells, purified as advanced therapy medicinal products, improve neuronal differentiation. Front Neurosci 2022; 16:1042276. [PMID: 36466172 PMCID: PMC9713000 DOI: 10.3389/fnins.2022.1042276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 11/04/2022] [Indexed: 04/11/2024] Open
Abstract
BACKGROUND Olfactory ecto-mesenchymal stem cells (OE-MSC) are mesenchymal stem cells derived from the lamina propria of the nasal mucosa. They display neurogenic and immunomodulatory properties and were shown to induce recovery in animal models of spinal cord trauma, hearing loss, Parkinsons's disease, amnesia, and peripheral nerve injury. As a step toward clinical practice, we sought to (i) devise a culture protocol that meets the requirements set by human health agencies and (ii) assess the efficacy of stem cells on neuron differentiation. METHODS Nasal olfactory mucosa biopsies from three donors were used to design and validate the good manufacturing process for purifying stem cells. All processes and procedures were performed by expert staff from the cell therapy laboratory of the public hospital of Marseille (AP-HM), according to aseptic handling manipulations. Premises, materials and air were kept clean at all times to avoid cross-contamination, accidents, or even fatalities. Purified stem cells were cultivated for 24 or 48 h and conditioned media were collected before being added to the culture medium of the neuroblastoma cell line Neuro2a. RESULTS Compared to the explant culture-based protocol, enzymatic digestion provides higher cell numbers more rapidly and is less prone to contamination. The use of platelet lysate in place of fetal calf serum is effective in promoting higher cell proliferation (the percentage of CFU-F progenitors is 15.5%), with the optimal percentage of platelet lysate being 10%. Cultured OE-MSCs do not show chromosomal rearrangement and, as expected, express the usual phenotypic markers of mesenchymal stem cells. When incorporated in standard culture medium, the conditioned medium of purified OE-MSCs promotes cell differentiation of Neuro2a neuroblastoma cells. CONCLUSION We developed a safer and more efficient manufacturing process for clinical grade olfactory stem cells. With this protocol, human OE-MSCs will soon be used in a Phase I clinical based on their autologous transplantation in digital nerves with a neglected injury. However, further studies are required to unveil the underlying mechanisms of action.
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Affiliation(s)
- Charlotte Jaloux
- CNRS, INP, UMR 7051, Institut de Neuropathophysiologie, Equipe Nasal Olfactory Stemness and Epigenesis (NOSE), Aix Marseille University, Marseille, France
- Department of Hand Surgery and Reconstructive Surgery of the Limbs, La Timone University Hospital, Assistance Publique Hôpitaux de Marseille, Marseille, France
| | - Maxime Bonnet
- CNRS, INP, UMR 7051, Institut de Neuropathophysiologie, Equipe Nasal Olfactory Stemness and Epigenesis (NOSE), Aix Marseille University, Marseille, France
- Faculté des Sciences du Sport de Marseille, CNRS, ISM, UMR 7287, Institut des Sciences du Mouvement Etienne-Jules MAREY, Equipe Plasticité des Systèmes Nerveux et Musculaire (PSNM), Parc Scientifique et Technologique de Luminy, Aix Marseille University, Marseille, France
| | - Marie Vogtensperger
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France
| | - Marie Witters
- CNRS, INP, UMR 7051, Institut de Neuropathophysiologie, Equipe Nasal Olfactory Stemness and Epigenesis (NOSE), Aix Marseille University, Marseille, France
- Department of Hand Surgery and Reconstructive Surgery of the Limbs, La Timone University Hospital, Assistance Publique Hôpitaux de Marseille, Marseille, France
| | - Julie Veran
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France
| | - Laurent Giraudo
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France
| | - Florence Sabatier
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France
- Aix-Marseille Université, C2VN, UMR-1263, INSERM, INRA 1260, UFR de Pharmacie, Marseille, France
| | - Justin Michel
- Department of Otorhinolaryngology and Head and Neck Surgery, Assistance Publique des Hôpitaux de Marseille, Institut Universitaire des Systèmes Thermiques Industriels, La Conception University Hospital, Aix Marseille University, Marseille, France
| | - Regis Legré
- Department of Hand Surgery and Reconstructive Surgery of the Limbs, La Timone University Hospital, Assistance Publique Hôpitaux de Marseille, Marseille, France
| | - Gaëlle Guiraudie-Capraz
- CNRS, INP, UMR 7051, Institut de Neuropathophysiologie, Equipe Nasal Olfactory Stemness and Epigenesis (NOSE), Aix Marseille University, Marseille, France
| | - François Féron
- CNRS, INP, UMR 7051, Institut de Neuropathophysiologie, Equipe Nasal Olfactory Stemness and Epigenesis (NOSE), Aix Marseille University, Marseille, France
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Qian W, Zhang M, Wan K, Xie Y, Du S, Li J, Mu X, Qiu J, Xue X, Zhuang X, Wu Y, Liu F, Wang S. Genetic evidence for facial variation being a composite phenotype of cranial variation and facial soft tissue thickness. J Genet Genomics 2022; 49:934-942. [DOI: 10.1016/j.jgg.2022.02.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 02/17/2022] [Accepted: 02/20/2022] [Indexed: 10/18/2022]
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He P, Ruan D, Huang Z, Wang C, Xu Y, Cai H, Liu H, Fei Y, Heng BC, Chen W, Shen W. Comparison of Tendon Development Versus Tendon Healing and Regeneration. Front Cell Dev Biol 2022; 10:821667. [PMID: 35141224 PMCID: PMC8819183 DOI: 10.3389/fcell.2022.821667] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 01/07/2022] [Indexed: 12/27/2022] Open
Abstract
Tendon is a vital connective tissue in human skeletal muscle system, and tendon injury is very common and intractable in clinic. Tendon development and repair are two closely related but still not fully understood processes. Tendon development involves multiple germ layer, as well as the regulation of diversity transcription factors (Scx et al.), proteins (Tnmd et al.) and signaling pathways (TGFβ et al.). The nature process of tendon repair is roughly divided in three stages, which are dominated by various cells and cell factors. This review will describe the whole process of tendon development and compare it with the process of tendon repair, focusing on the understanding and recent advances in the regulation of tendon development and repair. The study and comparison of tendon development and repair process can thus provide references and guidelines for treatment of tendon injuries.
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Affiliation(s)
- Peiwen He
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Institute of Sports Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Dengfeng Ruan
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Institute of Sports Medicine, Zhejiang University, Hangzhou, China
| | - Zizhan Huang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Institute of Sports Medicine, Zhejiang University, Hangzhou, China
| | - Canlong Wang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Institute of Sports Medicine, Zhejiang University, Hangzhou, China
| | - Yiwen Xu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Institute of Sports Medicine, Zhejiang University, Hangzhou, China
| | - Honglu Cai
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Institute of Sports Medicine, Zhejiang University, Hangzhou, China
| | - Hengzhi Liu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Institute of Sports Medicine, Zhejiang University, Hangzhou, China
| | - Yang Fei
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Institute of Sports Medicine, Zhejiang University, Hangzhou, China
| | - Boon Chin Heng
- Central Laboratory, Peking University School of Stomatology, Bejing, China
| | - Weishan Chen
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Institute of Sports Medicine, Zhejiang University, Hangzhou, China
- *Correspondence: Weishan Chen, ; Weiliang Shen,
| | - Weiliang Shen
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Institute of Sports Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, China
- China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China
- *Correspondence: Weishan Chen, ; Weiliang Shen,
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Sutton G, Kelsh RN, Scholpp S. Review: The Role of Wnt/β-Catenin Signalling in Neural Crest Development in Zebrafish. Front Cell Dev Biol 2021; 9:782445. [PMID: 34912811 PMCID: PMC8667473 DOI: 10.3389/fcell.2021.782445] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 11/16/2021] [Indexed: 12/20/2022] Open
Abstract
The neural crest (NC) is a multipotent cell population in vertebrate embryos with extraordinary migratory capacity. The NC is crucial for vertebrate development and forms a myriad of cell derivatives throughout the body, including pigment cells, neuronal cells of the peripheral nervous system, cardiomyocytes and skeletogenic cells in craniofacial tissue. NC induction occurs at the end of gastrulation when the multipotent population of NC progenitors emerges in the ectodermal germ layer in the neural plate border region. In the process of NC fate specification, fate-specific markers are expressed in multipotent progenitors, which subsequently adopt a specific fate. Thus, NC cells delaminate from the neural plate border and migrate extensively throughout the embryo until they differentiate into various cell derivatives. Multiple signalling pathways regulate the processes of NC induction and specification. This review explores the ongoing role of the Wnt/β-catenin signalling pathway during NC development, focusing on research undertaken in the Teleost model organism, zebrafish (Danio rerio). We discuss the function of the Wnt/β-catenin signalling pathway in inducing the NC within the neural plate border and the specification of melanocytes from the NC. The current understanding of NC development suggests a continual role of Wnt/β-catenin signalling in activating and maintaining the gene regulatory network during NC induction and pigment cell specification. We relate this to emerging models and hypotheses on NC fate restriction. Finally, we highlight the ongoing challenges facing NC research, current gaps in knowledge, and this field's potential future directions.
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Affiliation(s)
- Gemma Sutton
- Living Systems Institute, School of Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom
| | - Robert N. Kelsh
- Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom
| | - Steffen Scholpp
- Living Systems Institute, School of Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom
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Kelsh RN, Camargo Sosa K, Farjami S, Makeev V, Dawes JHP, Rocco A. Cyclical fate restriction: a new view of neural crest cell fate specification. Development 2021; 148:273451. [PMID: 35020872 DOI: 10.1242/dev.176057] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Neural crest cells are crucial in development, not least because of their remarkable multipotency. Early findings stimulated two hypotheses for how fate specification and commitment from fully multipotent neural crest cells might occur, progressive fate restriction (PFR) and direct fate restriction, differing in whether partially restricted intermediates were involved. Initially hotly debated, they remain unreconciled, although PFR has become favoured. However, testing of a PFR hypothesis of zebrafish pigment cell development refutes this view. We propose a novel 'cyclical fate restriction' hypothesis, based upon a more dynamic view of transcriptional states, reconciling the experimental evidence underpinning the traditional hypotheses.
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Affiliation(s)
- Robert N Kelsh
- Department of Biology & Biochemistry, University of Bath, Bath, BA2 7AY, UK
| | - Karen Camargo Sosa
- Department of Biology & Biochemistry, University of Bath, Bath, BA2 7AY, UK
| | - Saeed Farjami
- Department of Microbial Sciences, FHMS, University of Surrey, Guildford, GU2 7XH, UK
| | - Vsevolod Makeev
- Department of Computational Systems Biology, Vavilov Institute of General Genetics, Russian Academy of Sciences, Ul. Gubkina 3, Moscow, 119991, Russian Federation.,Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701, Russian Federation
| | - Jonathan H P Dawes
- Department of Mathematical Sciences, University of Bath, Bath, BA2 7AY, UK
| | - Andrea Rocco
- Department of Microbial Sciences, FHMS, University of Surrey, Guildford, GU2 7XH, UK.,Department of Physics, FEPS, University of Surrey, Guildford, GU2 7XH, UK
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Abstract
Neural crest stem/progenitor cells arise early during vertebrate embryogenesis at the border of the forming central nervous system. They subsequently migrate throughout the body, eventually differentiating into diverse cell types ranging from neurons and glia of the peripheral nervous system to bones of the face, portions of the heart, and pigmentation of the skin. Along the body axis, the neural crest is heterogeneous, with different subpopulations arising in the head, neck, trunk, and tail regions, each characterized by distinct migratory patterns and developmental potential. Modern genomic approaches like single-cell RNA- and ATAC-sequencing (seq) have greatly enhanced our understanding of cell lineage trajectories and gene regulatory circuitry underlying the developmental progression of neural crest cells. Here, we discuss how genomic approaches have provided new insights into old questions in neural crest biology by elucidating transcriptional and posttranscriptional mechanisms that govern neural crest formation and the establishment of axial level identity. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Shashank Gandhi
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA; ,
| | - Marianne E Bronner
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA; ,
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9
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Farina AR, Cappabianca LA, Zelli V, Sebastiano M, Mackay AR. Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting. World J Stem Cells 2021; 13:685-736. [PMID: 34367474 PMCID: PMC8316860 DOI: 10.4252/wjsc.v13.i7.685] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/09/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023] Open
Abstract
Pediatric neuroblastomas (NBs) are heterogeneous, aggressive, therapy-resistant embryonal tumours that originate from cells of neural crest (NC) origin and in particular neuroblasts committed to the sympathoadrenal progenitor cell lineage. Therapeutic resistance, post-therapeutic relapse and subsequent metastatic NB progression are driven primarily by cancer stem cell (CSC)-like subpopulations, which through their self-renewing capacity, intermittent and slow cell cycles, drug-resistant and reversibly adaptive plastic phenotypes, represent the most important obstacle to improving therapeutic outcomes in unfavourable NBs. In this review, dedicated to NB CSCs and the prospects for their therapeutic eradication, we initiate with brief descriptions of the unique transient vertebrate embryonic NC structure and salient molecular protagonists involved NC induction, specification, epithelial to mesenchymal transition and migratory behaviour, in order to familiarise the reader with the embryonic cellular and molecular origins and background to NB. We follow this by introducing NB and the potential NC-derived stem/progenitor cell origins of NBs, before providing a comprehensive review of the salient molecules, signalling pathways, mechanisms, tumour microenvironmental and therapeutic conditions involved in promoting, selecting and maintaining NB CSC subpopulations, and that underpin their therapy-resistant, self-renewing metastatic behaviour. Finally, we review potential therapeutic strategies and future prospects for targeting and eradication of these bastions of NB therapeutic resistance, post-therapeutic relapse and metastatic progression.
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Affiliation(s)
- Antonietta Rosella Farina
- Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, AQ, Italy
| | - Lucia Annamaria Cappabianca
- Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, AQ, Italy
| | - Veronica Zelli
- Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, AQ, Italy
| | - Michela Sebastiano
- Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, AQ, Italy
| | - Andrew Reay Mackay
- Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, AQ, Italy.
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Unachukwu U, Shiomi T, Goldklang M, Chada K, D'Armiento J. Renal neoplasms in tuberous sclerosis mice are neurocristopathies. iScience 2021; 24:102684. [PMID: 34222844 PMCID: PMC8243016 DOI: 10.1016/j.isci.2021.102684] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 04/20/2021] [Accepted: 05/31/2021] [Indexed: 11/13/2022] Open
Abstract
Tuberous sclerosis (TS) is a rare disorder exhibiting multi-systemic benign neoplasms. We hypothesized the origin of TS neoplastic cells derived from the neural crest given the heterogeneous ecto-mesenchymal phenotype of the most common TS neoplasms. To test this hypothesis, we employed Cre-loxP lineage tracing of myelin protein zero (Mpz)-expressing neural crest cells (NCCs) in spontaneously developing renal tumors of Tsc2 +/- /Mpz(Cre)/TdT fl/fl reporter mice. In these mice, ectopic renal tumor onset was detected at 4 months of age increasing in volume by 16 months of age with concomitant increase in the subpopulation of tdTomato+ NCCs from 0% to 6.45% of the total number of renal tumor cells. Our results suggest that Tsc2 +/- mouse renal tumors arise from domiciled proliferative progenitor cell populations of neural crest origin that co-opt tumorigenesis due to mutations in Tsc2 loci. Targeting neural crest antigenic determinants will provide a potential alternative therapeutic approach for TS pathogenesis.
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Affiliation(s)
- Uchenna Unachukwu
- Center for LAM and Rare Lung Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, USA
| | - Takayuki Shiomi
- Department of Pathology, International University of Health and Welfare, School of Medicine, 4-3 Kouzunomori, Narita-shi, Chiba 286-8686, Japan
| | - Monica Goldklang
- Center for LAM and Rare Lung Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, USA
| | - Kiran Chada
- Department of Biochemistry, Rutgers-Robert Wood Johnson Medical School, Rutgers University, 675 Hoes Lane, Piscataway, NJ 08854, USA
| | - Jeanine D'Armiento
- Center for LAM and Rare Lung Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, USA
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Artinger KB, Monsoro-Burq AH. Neural crest multipotency and specification: power and limits of single cell transcriptomic approaches. Fac Rev 2021; 10:38. [PMID: 34046642 PMCID: PMC8130411 DOI: 10.12703/r/10-38] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
The neural crest is a unique population of multipotent cells forming in vertebrate embryos. Their vast cell fate potential enables the generation of a diverse array of differentiated cell types in vivo. These include, among others, connective tissue, cartilage and bone of the face and skull, neurons and glia of the peripheral nervous system (including enteric nervous system), and melanocytes. Following migration, these derivatives extensively populate multiple germ layers. Within the competent neural border ectoderm, an area located at the junction between the neural and non-neural ectoderm during embryonic development, neural crest cells form in response to a series of inductive secreted cues including BMP, Wnt, and FGF signals. As cells become progressively specified, they express transcriptional modules conducive with their stage of fate determination or cell state. Those sequential states include the neural border state, the premigratory neural crest state, the epithelium-to-mesenchyme transitional state, and the migratory state to end with post-migratory and differentiation states. However, despite the extensive knowledge accumulated over 150 years of neural crest biology, many key questions remain open, in particular the timing of neural crest lineage determination, the control of potency during early developmental stages, and the lineage relationships between different subpopulations of neural crest cells. In this review, we discuss the recent advances in understanding early neural crest formation using cutting-edge high-throughput single cell sequencing approaches. We will discuss how this new transcriptomic data, from 2017 to 2021, has advanced our knowledge of the steps in neural crest cell lineage commitment and specification, the mechanisms driving multipotency, and diversification. We will then discuss the questions that remain to be resolved and how these approaches may continue to unveil the biology of these fascinating cells.
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Affiliation(s)
- Kristin B Artinger
- Department of Craniofacial Biology, University of Colorado School of Dental Medicine, Aurora, CO, USA
| | - Anne H Monsoro-Burq
- Université Paris-Saclay, Faculté des Sciences d'Orsay, France
- Institut Curie, INSERM U1021, CNRS UMR3347, Orsay, France
- Institut Universitaire de France, Paris, France
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12
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Höving AL, Windmöller BA, Knabbe C, Kaltschmidt B, Kaltschmidt C, Greiner JFW. Between Fate Choice and Self-Renewal-Heterogeneity of Adult Neural Crest-Derived Stem Cells. Front Cell Dev Biol 2021; 9:662754. [PMID: 33898464 PMCID: PMC8060484 DOI: 10.3389/fcell.2021.662754] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 03/18/2021] [Indexed: 12/16/2022] Open
Abstract
Stem cells of the neural crest (NC) vitally participate to embryonic development, but also remain in distinct niches as quiescent neural crest-derived stem cell (NCSC) pools into adulthood. Although NCSC-populations share a high capacity for self-renewal and differentiation resulting in promising preclinical applications within the last two decades, inter- and intrapopulational differences exist in terms of their expression signatures and regenerative capability. Differentiation and self-renewal of stem cells in developmental and regenerative contexts are partially regulated by the niche or culture condition and further influenced by single cell decision processes, making cell-to-cell variation and heterogeneity critical for understanding adult stem cell populations. The present review summarizes current knowledge of the cellular heterogeneity within NCSC-populations located in distinct craniofacial and trunk niches including the nasal cavity, olfactory bulb, oral tissues or skin. We shed light on the impact of intrapopulational heterogeneity on fate specifications and plasticity of NCSCs in their niches in vivo as well as during in vitro culture. We further discuss underlying molecular regulators determining fate specifications of NCSCs, suggesting a regulatory network including NF-κB and NC-related transcription factors like SLUG and SOX9 accompanied by Wnt- and MAPK-signaling to orchestrate NCSC stemness and differentiation. In summary, adult NCSCs show a broad heterogeneity on the level of the donor and the donors' sex, the cell population and the single stem cell directly impacting their differentiation capability and fate choices in vivo and in vitro. The findings discussed here emphasize heterogeneity of NCSCs as a crucial parameter for understanding their role in tissue homeostasis and regeneration and for improving their applicability in regenerative medicine.
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Affiliation(s)
- Anna L. Höving
- Department of Cell Biology, University of Bielefeld, Bielefeld, Germany
- Institute for Laboratory- and Transfusion Medicine, Heart and Diabetes Centre North Rhine-Westphalia (NRW), Ruhr University Bochum, Bad Oeynhausen, Germany
| | - Beatrice A. Windmöller
- Department of Cell Biology, University of Bielefeld, Bielefeld, Germany
- Forschungsverbund BioMedizin Bielefeld FBMB e.V., Bielefeld, Germany
| | - Cornelius Knabbe
- Institute for Laboratory- and Transfusion Medicine, Heart and Diabetes Centre North Rhine-Westphalia (NRW), Ruhr University Bochum, Bad Oeynhausen, Germany
- Forschungsverbund BioMedizin Bielefeld FBMB e.V., Bielefeld, Germany
| | - Barbara Kaltschmidt
- Department of Cell Biology, University of Bielefeld, Bielefeld, Germany
- Forschungsverbund BioMedizin Bielefeld FBMB e.V., Bielefeld, Germany
- Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany
| | - Christian Kaltschmidt
- Department of Cell Biology, University of Bielefeld, Bielefeld, Germany
- Forschungsverbund BioMedizin Bielefeld FBMB e.V., Bielefeld, Germany
| | - Johannes F. W. Greiner
- Department of Cell Biology, University of Bielefeld, Bielefeld, Germany
- Forschungsverbund BioMedizin Bielefeld FBMB e.V., Bielefeld, Germany
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13
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Yoshida H, Suzawa T, Shibata Y, Takahashi M, Kawai R, Takami M, Maki K, Kamijo R. Neural crest-derived cells in nasal conchae of adult mice contribute to bone regeneration. Biochem Biophys Res Commun 2021; 554:173-178. [PMID: 33798944 DOI: 10.1016/j.bbrc.2021.03.079] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 03/15/2021] [Indexed: 01/02/2023]
Abstract
Neural crest-derived cells (NCDCs), a class of adult stem cells not restricted to embryonic tissues, are attractive tissue regenerative therapy candidates because of their ease of isolation, self-renewing properties, and multipotency. Although adult NCDCs can undergo osteogenic differentiation in vitro, whether they induce bone formation in vivo remains unclear. Previously, our group reported findings showing high amounts of NCDCs scattered throughout nasal concha tissues of adult mice. In the present study, NCDCs in nasal conchae labeled with enhanced green fluorescent protein (EGFP) were collected from adult P0-Cre/CAG-CAT-EGFP double transgenic mice, then cultured in serum-free medium to increase the number. Subsequently, NCDCs were harvested and suspended in type I atelocollagen gel, then an atelocollagen sponge was used as a scaffold for the cell suspension. Atelocollagen scaffolds with NCDCs were placed on bone defects created in a mouse calvarial bone defect model. Over the ensuing 12 weeks, micro-CT and histological analysis findings showed that mice with scaffolds containing NCDCs had slightly greater bone formation as compared to those with a scaffold alone. Furthermore, Raman spectroscopy revealed spectral properties of bone in mice that received scaffolds with NCDCs similar to those of native calvarial bone. Bone regeneration is important not only for gaining bone mass but also chemical properties. These results are the first to show the validity of biomolecule-free adult nasal concha-derived NCDCs for bone regeneration, including the chemical properties of regenerated bone tissue.
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Affiliation(s)
- Hiroshi Yoshida
- Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan; Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan
| | - Tetsuo Suzawa
- Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
| | - Yo Shibata
- Department of Conservative Dentistry, Division of Biomaterials and Engineering, School of Dentistry, Showa University, Tokyo, Japan
| | - Masahiro Takahashi
- Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan
| | - Ryota Kawai
- Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan
| | - Masamichi Takami
- Department of Pharmacology, School of Dentistry, Showa University, Tokyo, Japan
| | - Koutaro Maki
- Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan
| | - Ryutaro Kamijo
- Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan
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14
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Petratou K, Spencer SA, Kelsh RN, Lister JA. The MITF paralog tfec is required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor. PLoS One 2021; 16:e0244794. [PMID: 33439865 PMCID: PMC7806166 DOI: 10.1371/journal.pone.0244794] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 11/29/2020] [Indexed: 12/12/2022] Open
Abstract
Understanding how fate specification of distinct cell-types from multipotent progenitors occurs is a fundamental question in embryology. Neural crest stem cells (NCSCs) generate extraordinarily diverse derivatives, including multiple neural, skeletogenic and pigment cell fates. Key transcription factors and extracellular signals specifying NCSC lineages remain to be identified, and we have only a little idea of how and when they function together to control fate. Zebrafish have three neural crest-derived pigment cell types, black melanocytes, light-reflecting iridophores and yellow xanthophores, which offer a powerful model for studying the molecular and cellular mechanisms of fate segregation. Mitfa has been identified as the master regulator of melanocyte fate. Here, we show that an Mitf-related transcription factor, Tfec, functions as master regulator of the iridophore fate. Surprisingly, our phenotypic analysis of tfec mutants demonstrates that Tfec also functions in the initial specification of all three pigment cell-types, although the melanocyte and xanthophore lineages recover later. We show that Mitfa represses tfec expression, revealing a likely mechanism contributing to the decision between melanocyte and iridophore fate. Our data are consistent with the long-standing proposal of a tripotent progenitor restricted to pigment cell fates. Moreover, we investigate activation, maintenance and function of tfec in multipotent NCSCs, demonstrating for the first time its role in the gene regulatory network forming and maintaining early neural crest cells. In summary, we build on our previous work to characterise the gene regulatory network governing iridophore development, establishing Tfec as the master regulator driving iridophore specification from multipotent progenitors, while shedding light on possible cellular mechanisms of progressive fate restriction.
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Affiliation(s)
- Kleio Petratou
- Department of Biology and Biochemistry and Centre for Regenerative Medicine, University of Bath, Bath, United Kingdom
| | - Samantha A. Spencer
- Department of Human and Molecular Genetics and Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America
| | - Robert N. Kelsh
- Department of Biology and Biochemistry and Centre for Regenerative Medicine, University of Bath, Bath, United Kingdom
| | - James A. Lister
- Department of Human and Molecular Genetics and Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America
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15
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Bayat AH, Saeidikhoo S, Ebrahimi V, Mesgar S, Joneidi M, Soltani R, Aghajanpour F, Mohammadzadeh I, Torabi A, Abdollahifar MA, Bagher Z, Alizadeh R, Aliaghaei A. Bilateral striatal transplantation of human olfactory stem cells ameliorates motor function, prevents necroptosis-induced cell death and improves striatal volume in the rat model of Huntington's disease. J Chem Neuroanat 2020; 112:101903. [PMID: 33278568 DOI: 10.1016/j.jchemneu.2020.101903] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 10/27/2020] [Accepted: 11/30/2020] [Indexed: 01/02/2023]
Abstract
Cellular transplant therapy is one of the most common therapeutic strategies used to mitigate symptoms of neurodegenerative diseases such as Huntington's disease (HD). Briefly, the main goal of the present study was to investigate HD's motor deficits through the olfactory ecto-mesenchymals stem cells (OE-MSC) secretome. OE-MSCs were characterized immunophenotypically by the positive expression of CD73, CD90 and CD105. Also, three specific markers of OE-MSCs were obtained from the nasal cavity of human volunteers. The main features of OE-MSCs are their high proliferation, ease of harvesting and growth factor secretion. All animals were randomly assigned to three groups: control, 3-NP + vehicle treated and 3-NP + Cell groups. In both experimental groups, the subjects received intraperitoneal 3-NP (30 mg/kg) injections once a day for five consecutive days, followed by the bilateral intra-striatal implantation of OE-MSCs in the 3-NP + Cell group. Muscular function was assessed by electromyography and rotarod test, and the locomotor function was evaluated using the open field test. According to our findings, striatal transplants of OE-MSCs reduced microglial inflammatory factor, the tumor necrosis factor (TNFα) in the 3-NP + Cell group, with a significant reduction in RIP3, the markers of necroptosis in striatum. In addition to the remarkable recovery of the striatal volume after engraftment, the motor activities were enhanced in the 3-NP + cell group compared to the 3-NP + vehicle group. Taken together, our results demonstrated the in vivo advantages of OE-MSCs treatment in an HD rat model with numerous positive paracrine effects including behavioral and anatomical recovery.
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Affiliation(s)
- Amir-Hossein Bayat
- Department of Neuroscience, Saveh University of Medical Sciences, Saveh, Iran.
| | - Sara Saeidikhoo
- Neuroscience Lab, Anatomy and Cell Biology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Vahid Ebrahimi
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Somaye Mesgar
- Neuroscience Lab, Anatomy and Cell Biology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammadjavad Joneidi
- Neuroscience Lab, Anatomy and Cell Biology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Reza Soltani
- Neuroscience Lab, Anatomy and Cell Biology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Fakhroddin Aghajanpour
- Neuroscience Lab, Anatomy and Cell Biology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Ibrahim Mohammadzadeh
- Neuroscience Lab, Anatomy and Cell Biology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Abolfazl Torabi
- Neuroscience Lab, Anatomy and Cell Biology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammad-Amin Abdollahifar
- Neuroscience Lab, Anatomy and Cell Biology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Zohreh Bagher
- ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, The Five Senses Health Institute, Iran University of Medical Sciences, Tehran, Iran.
| | - Rafieh Alizadeh
- ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, The Five Senses Health Institute, Iran University of Medical Sciences, Tehran, Iran.
| | - Abbas Aliaghaei
- Neuroscience Lab, Anatomy and Cell Biology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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16
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Perera SN, Kerosuo L. On the road again: Establishment and maintenance of stemness in the neural crest from embryo to adulthood. STEM CELLS (DAYTON, OHIO) 2020; 39:7-25. [PMID: 33017496 PMCID: PMC7821161 DOI: 10.1002/stem.3283] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 09/08/2020] [Accepted: 09/11/2020] [Indexed: 12/22/2022]
Abstract
Unique to vertebrates, the neural crest (NC) is an embryonic stem cell population that contributes to a greatly expanding list of derivatives ranging from neurons and glia of the peripheral nervous system, facial cartilage and bone, pigment cells of the skin to secretory cells of the endocrine system. Here, we focus on what is specifically known about establishment and maintenance of NC stemness and ultimate fate commitment mechanisms, which could help explain its exceptionally high stem cell potential that exceeds the "rules set during gastrulation." In fact, recent discoveries have shed light on the existence of NC cells that coexpress commonly accepted pluripotency factors like Nanog, Oct4/PouV, and Klf4. The coexpression of pluripotency factors together with the exceptional array of diverse NC derivatives encouraged us to propose a new term "pleistopotent" (Greek for abundant, a substantial amount) to be used to reflect the uniqueness of the NC as compared to other post-gastrulation stem cell populations in the vertebrate body, and to differentiate them from multipotent lineage restricted stem cells. We also discuss studies related to the maintenance of NC stemness within the challenging context of being a transient and thus a constantly changing population of stem cells without a permanent niche. The discovery of the stem cell potential of Schwann cell precursors as well as multiple adult NC-derived stem cell reservoirs during the past decade has greatly increased our understanding of how NC cells contribute to tissues formed after its initial migration stage in young embryos.
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Affiliation(s)
- Surangi N Perera
- Neural Crest Development and Disease Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA
| | - Laura Kerosuo
- Neural Crest Development and Disease Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA
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17
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Ghoubay D, Borderie M, Grieve K, Martos R, Bocheux R, Nguyen TM, Callard P, Chédotal A, Borderie VM. Corneal stromal stem cells restore transparency after N 2 injury in mice. Stem Cells Transl Med 2020; 9:917-935. [PMID: 32379938 PMCID: PMC7381812 DOI: 10.1002/sctm.19-0306] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 03/23/2020] [Accepted: 03/27/2020] [Indexed: 12/12/2022] Open
Abstract
Corneal scarring associated with various corneal conditions is a leading cause of blindness worldwide. The present study aimed to test the hypothesis that corneal stromal stem cells have a therapeutic effect and are able to restore the extracellular matrix organization and corneal transparency in vivo. We first developed a mouse model of corneal stromal scar induced by liquid nitrogen (N2) application. We then reversed stromal scarring by injecting mouse or human corneal stromal stem cells in injured cornea. To characterize the mouse model developed in this study and the therapeutic effect of corneal stromal stem cells, we used a combination of in vivo (slit lamp, optical coherence tomography, in vivo confocal microscopy, optical coherence tomography shear wave elastography, and optokinetic tracking response) and ex vivo (full field optical coherence microscopy, flow cytometry, transmission electron microscopy, and histology) techniques. The mouse model obtained features early inflammation, keratocyte apoptosis, keratocyte transformation into myofibroblasts, collagen type III synthesis, impaired stromal ultrastructure, corneal stromal haze formation, increased corneal rigidity, and impaired visual acuity. Injection of stromal stem cells in N2‐injured cornea resulted in improved corneal transparency associated with corneal stromal stem cell migration and growth in the recipient stroma, absence of inflammatory response, recipient corneal epithelial cell growth, decreased collagen type III stromal content, restored stromal ultrastructure, decreased stromal haze, decreased corneal rigidity, and improved vision. Our study demonstrates the ability of corneal stromal stem cells to promote regeneration of transparent stromal tissue after corneal scarring induced by liquid nitrogen.
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Affiliation(s)
- Djida Ghoubay
- Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France.,Centre Hospitalier National d'Ophtalmologie des 15-20, DHU Sight Restore, INSERM-DHOS CIC, Paris, France
| | - Marie Borderie
- Centre Hospitalier National d'Ophtalmologie des 15-20, DHU Sight Restore, INSERM-DHOS CIC, Paris, France
| | - Kate Grieve
- Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
| | - Raphaël Martos
- Laboratoire de Recherche Vasculaire Translationnelle, INSERM U1148, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Romain Bocheux
- Laboratoire d'Optique et Biosciences (LOB) École polytechnique, CNRS UMR 7645, INSERM U 1182, Palaiseau cedex, France
| | - Thu-Mai Nguyen
- Institut Langevin Ondes et images CNRS UMR 7587, INSERM U979 Physiques des ondes pour la médecine, ESPCI, Paris, France
| | - Patrice Callard
- Sorbonne Université, APHP, Hôpital Pitié Salpêtrière, Paris, France
| | - Alain Chédotal
- Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
| | - Vincent M Borderie
- Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France.,Centre Hospitalier National d'Ophtalmologie des 15-20, DHU Sight Restore, INSERM-DHOS CIC, Paris, France
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18
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Teixeira BL, Amarante-Silva D, Visoni SB, Garcez RC, Trentin AG. FGF2 Stimulates the Growth and Improves the Melanocytic Commitment of Trunk Neural Crest Cells. Cell Mol Neurobiol 2020; 40:383-393. [PMID: 31555941 PMCID: PMC11448768 DOI: 10.1007/s10571-019-00738-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Accepted: 09/14/2019] [Indexed: 12/13/2022]
Abstract
Neural crest cells (NCCs) comprise a population of multipotent progenitors and stem cells at the origin of the peripheral nervous system (PNS) and melanocytes of skin, which are profoundly influenced by microenvironmental factors, among which is basic fibroblast growth factor 2 (FGF2). In this work, we further investigated the role of this growth factor in quail trunk NC morphogenesis and demonstrated its huge effect in NCC growth mainly by stimulating cell proliferation but also reducing cell death, despite that NCC migration from the neural tube explant was not affected. Moreover, following FGF2 treatment, reduced expression of the early NC markers Sox10 and FoxD3 and improved proliferation of HNK1-positive NCC were observed. Since these markers are involved in the regulation of glial and melanocytic fate of NC, the effect of FGF2 on NCC differentiation was investigated. Therefore, in the presence of FGF2, increased proportions of NCCs positives to the melanoblast marker Mitf as well as NCCs double stained to Mitf and BrdU were recorded. In addition, treatment with FGF2, followed by differentiation medium, resulted in increased expression of melanin and improved proportion of melanin-pigmented melanocytes without alteration in the glial marker Schwann myelin protein (SMP). Taken together, these data further reveal the important role of FGF2 in NCC proliferation, survival, and differentiation, particularly in melanocyte development. This is the first demonstration of FGF2 effects in melanocyte commitment of NC and in the proliferation of Mitf-positive melanoblasts. Elucidating the differentiation process of embryonic NCCs brings us a step closer to understanding the development of the PNS and then undertaking the search for advanced technologies to prevent, or treat, injuries caused by NC-related disorders, also known as neurocristopathies.
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Affiliation(s)
- Bianca Luise Teixeira
- Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis-SC, Campus Universitário,Trindade, Florianópolis, SC, 88040-900, Brazil
| | - Diego Amarante-Silva
- Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis-SC, Campus Universitário,Trindade, Florianópolis, SC, 88040-900, Brazil
| | - Silvia Beatriz Visoni
- Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis-SC, Campus Universitário,Trindade, Florianópolis, SC, 88040-900, Brazil
| | - Ricardo Castilho Garcez
- Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis-SC, Campus Universitário,Trindade, Florianópolis, SC, 88040-900, Brazil
| | - Andrea Gonçalves Trentin
- Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis-SC, Campus Universitário,Trindade, Florianópolis, SC, 88040-900, Brazil.
- National Institute of Science and Technology for Regenerative Medicine, Av. Carlos Chagas Filho, n°373, Rio De Janeiro, RJ, CEP: 21941902, Brazil.
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19
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Alizadeh R, Ramezanpour F, Mohammadi A, Eftekharzadeh M, Simorgh S, Kazemiha M, Moradi F. Differentiation of human olfactory system-derived stem cells into dopaminergic neuron-like cells: A comparison between olfactory bulb and mucosa as two sources of stem cells. J Cell Biochem 2019; 120:19712-19720. [PMID: 31297865 DOI: 10.1002/jcb.29277] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 06/20/2019] [Indexed: 12/11/2022]
Abstract
Cell transplantation has become a possible therapeutic approach in the treatment of neurodegenerative diseases of the nervous system by replacing lost cells. The current study aimed to make a comparison between the differentiation capacity of the olfactory bulb neural stem cells (OB-NSCs) and olfactory ectomesenchymal stem cells (OE-MSCs) into dopaminergic-like neurons under the inductive effect of transforming growth factor β (TGF-β). After culturing and treating with TGF-β, the differentiation capacities of both types of stem cells into dopaminergic neuron-like cells were evaluated. Quantitative real-time polymerase chain reaction analysis 3 weeks after induction demonstrated that the mRNA expression of the dopaminergic activity markers tyrosine hydroxylase (TH), dopamine transporter (DAT), paired box gene 2 (PAX2), and PAX5 in the neuron-like cells derived from OB-NSCs was significantly higher than those derived from OE-MSCs. These findings were further supported by the immunocytochemistry staining showing that the expression of the tyrosine hydroxylase, DAT, PAX2, and paired like homeodomain 3 seemed to be slightly higher in OB-NSCs compared with OE-MSCs. Despite the lower differentiation capacity of OE-MSCs, other considerations such as a noninvasive and easier harvesting process, faster proliferation attributes, longer life span, autologous transplantability, and also the easier and inexpensive cultural process of the OE-MSCs, cumulatively make these cells the more appropriate alternative in the case of autologous transplantation during the treatment process of neurodegenerative disorders like Parkinson's disease.
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Affiliation(s)
- Rafieh Alizadeh
- ENT and Head & Neck Research Center and Department, The Five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Farnaz Ramezanpour
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Mohammadi
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mina Eftekharzadeh
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Sara Simorgh
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Milad Kazemiha
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Moradi
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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20
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Beppu M, Nakagomi T, Takagi T, Nakano-Doi A, Sakuma R, Kuramoto Y, Tatebayashi K, Matsuyama T, Yoshimura S. Isolation and Characterization of Cerebellum-Derived Stem Cells in Poststroke Human Brain. Stem Cells Dev 2019; 28:528-542. [PMID: 30767605 DOI: 10.1089/scd.2018.0232] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
There is compelling evidence that the mature central nervous system (CNS) harbors stem cell populations outside conventional neurogenic regions. We previously demonstrated that brain pericytes (PCs) in both mouse and human exhibit multipotency to differentiate into various neural lineages following cerebral ischemia. PCs are found throughout the CNS, including cerebellum, but it remains unclear whether cerebellar PCs also form ischemia-induced multipotent stem cells (iSCs). In this study, we demonstrate that putative iSCs can be isolated from poststroke human cerebellum (cerebellar iSCs [cl-iSCs]). These cl-iSCs exhibited multipotency and differentiated into electrophysiologically active neurons. Neurogenic potential was also confirmed in single-cell suspensions. DNA microarray analysis revealed highly similar gene expression patterns between PCs and cl-iSCs, suggesting PC origin. Global gene expression comparison with cerebral iSCs revealed general similarity, but cl-iSCs differentially expressed certain cerebellum-specific genes. Thus, putative iSCs are present in poststroke cerebellum and possess region-specific traits, suggesting potential capacity to regenerate functional cerebellar neurons following ischemic stroke.
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Affiliation(s)
- Mikiya Beppu
- 1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Takayuki Nakagomi
- 2 Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan.,3 Department of Therapeutic Progress in Brain Diseases, Hyogo College of Medicine, Nishinomiya, Japan
| | - Toshinori Takagi
- 1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Akiko Nakano-Doi
- 2 Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan.,3 Department of Therapeutic Progress in Brain Diseases, Hyogo College of Medicine, Nishinomiya, Japan
| | - Rika Sakuma
- 2 Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan
| | - Yoji Kuramoto
- 1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Kotaro Tatebayashi
- 1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Tomohiro Matsuyama
- 3 Department of Therapeutic Progress in Brain Diseases, Hyogo College of Medicine, Nishinomiya, Japan
| | - Shinichi Yoshimura
- 1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan
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21
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Etchevers HC, Dupin E, Le Douarin NM. The diverse neural crest: from embryology to human pathology. Development 2019; 146:146/5/dev169821. [PMID: 30858200 DOI: 10.1242/dev.169821] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 02/07/2019] [Indexed: 01/13/2023]
Abstract
We review here some of the historical highlights in exploratory studies of the vertebrate embryonic structure known as the neural crest. The study of the molecular properties of the cells that it produces, their migratory capacities and plasticity, and the still-growing list of tissues that depend on their presence for form and function, continue to enrich our understanding of congenital malformations, paediatric cancers and evolutionary biology. Developmental biology has been key to our understanding of the neural crest, starting with the early days of experimental embryology and through to today, when increasingly powerful technologies contribute to further insight into this fascinating vertebrate cell population.
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Affiliation(s)
- Heather C Etchevers
- Aix-Marseille Université, INSERM, MMG, U1251, 27 boulevard Jean Moulin 13005 Marseille, France
| | - Elisabeth Dupin
- Sorbonne Universités, UPMC Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France
| | - Nicole M Le Douarin
- Sorbonne Universités, UPMC Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France
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22
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Tanaka M. Embryological Consideration of Dural AVFs in Relation to the Neural Crest and the Mesoderm. Neurointervention 2019; 14:9-16. [PMID: 30827062 PMCID: PMC6433192 DOI: 10.5469/neuroint.2018.01095] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2018] [Revised: 01/29/2019] [Accepted: 02/15/2019] [Indexed: 01/08/2023] Open
Abstract
Intracranial and spinal dural arteriovenous fistulas (DAVFs) are vascular pathologies of the dural membrane with arteriovenous shunts. They are abnormal communications between arteries and veins or dural venous sinuses that sit between the two sheets of the dura mater. The dura propria faces the surface of brain, and the osteal dura faces the bone. The location of the shunt points is not distributed homogeneously on the surface of the dural membrane, but there are certain areas susceptible to DAVFs. The dura mater of the olfactory groove, falx cerebri, inferior sagittal sinus, tentorium cerebelli, and falx cerebelli, and the dura mater at the level of the spinal cord are composed only of dura propria, and these areas are derived from neural crest cells. The dura mater of the cavernous sinus, transverse sinus, sigmoid sinus, and anterior condylar confluence surrounding the hypoglossal canal are composed of both dura propria and osteal dura; this group is derived from mesoderm. Although the cause of this heterogeneity has not yet been determined, there are some specific characteristics and tendencies in terms of the embryological features. The possible reasons for the segmental susceptibility to DAVFs are summarized based on the embryology of the dura mater.
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Affiliation(s)
- Michihiro Tanaka
- Department of Neurosurgery, Kameda Medical Center, Kamogawa, Japan
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23
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Head to Knee: Cranial Neural Crest-Derived Cells as Promising Candidates for Human Cartilage Repair. Stem Cells Int 2019; 2019:9310318. [PMID: 30766608 PMCID: PMC6350557 DOI: 10.1155/2019/9310318] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 11/04/2018] [Accepted: 12/06/2018] [Indexed: 12/13/2022] Open
Abstract
A large array of therapeutic procedures is available to treat cartilage disorders caused by trauma or inflammatory disease. Most are invasive and may result in treatment failure or development of osteoarthritis due to extensive cartilage damage from repeated surgery. Despite encouraging results of early cell therapy trials that used chondrocytes collected during arthroscopic surgery, these approaches have serious disadvantages, including morbidity associated with cell harvesting and low predictive clinical outcomes. To overcome these limitations, adult stem cells derived from bone marrow and subsequently from other tissues are now considered as preferred sources of cells for cartilage regeneration. Moreover, with new evidence showing that the choice of cell source is one of the most important factors for successful cell therapy, there is growing interest in neural crest-derived cells in both the research and clinical communities. Neural crest-derived cells such as nasal chondrocytes and oral stem cells that exhibit chondrocyte-like properties seem particularly promising in cartilage repair. Here, we review the types of cells currently available for cartilage cell therapy, including articular chondrocytes and various mesenchymal stem cells, and then highlight recent developments in the use of neural crest-derived chondrocytes and oral stem cells for repair of cartilage lesions.
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Alizadeh R, Bagher Z, Kamrava SK, Falah M, Ghasemi Hamidabadi H, Eskandarian Boroujeni M, Mohammadi F, Khodaverdi S, Zare-Sadeghi A, Olya A, Komeili A. Differentiation of human mesenchymal stem cells (MSC) to dopaminergic neurons: A comparison between Wharton's Jelly and olfactory mucosa as sources of MSCs. J Chem Neuroanat 2019; 96:126-133. [PMID: 30639339 DOI: 10.1016/j.jchemneu.2019.01.003] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Revised: 12/15/2018] [Accepted: 01/09/2019] [Indexed: 12/28/2022]
Abstract
The generation of dopaminergic neurons from stem cells is a potential therapeutic approach to treat neurodegenerative disorders, such as Parkinson's disease. The current study aims to investigate the potential of two different types of mesenchymal stem cells derived from human Wharton's jelly and nasal cavity for differentiation into dopaminergic neurons. The differentiation capacities of both cell types were evaluated using real-time PCR, immunocytochemistry, flow cytometry and HPLC. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are noted for their capability to differentiate into mesodermal and non-mesodermal cells, including neurons. However, it was demonstrated that having the same neuroectodermal origin as the nervous system, the olfactory ectomesenchymal stem cells (OE-MSCs) expressed the neural marker MAP2 as well as dopaminergic markers such as tyrosine hydroxylase (TH), dopamine transporter (DAT) and PITX3 to a greater extent than the WJ-MSCs both at the level of mRNA and protein. Furthermore, quantitative flow cytometric evaluation of these markers at 12 days post-induction supported the above-mentioned results. Finally, the assessment of the functionality of differentiated cells and their ability to synthesize dopamine measured by HPLC revealed that the OE-MSC-derived dopaminergic cells released almost the same amount of dopamine as that secreted by WJ-MSC-derived cells. Thus it showed the difference in their functionality to be negligible. Overall, it may be concluded that higher proliferation and differentiation capacity of OE-MSCs, along with their easier harvestability and autologous transplantability compared with WJ-MSCs, makes them a better cell source for stem cell therapy of neurodegenerative disorders which are caused by degeneration of dopaminergic neurons.
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Affiliation(s)
- Rafieh Alizadeh
- ENT and Head & Neck Research Center and Department, The five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Zohreh Bagher
- ENT and Head & Neck Research Center and Department, The five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Seyed Kamran Kamrava
- ENT and Head & Neck Research Center and Department, The five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Falah
- ENT and Head & Neck Research Center and Department, The five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Hatef Ghasemi Hamidabadi
- Department of Anatomy & Cell Biology, Immunogenetic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mahdi Eskandarian Boroujeni
- Department of Stem Cells and Regenerative Medicine, Faculty of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Fatemeh Mohammadi
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Sepideh Khodaverdi
- Endometriosis Research Center, University of Medical Sciences, Tehran, Iran
| | - Arash Zare-Sadeghi
- Skull Base Research Center, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Arta Olya
- Department of Stem Cells and Regenerative Medicine, Faculty of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Ali Komeili
- Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran.
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Replogle MR, Sreevidya VS, Lee VM, Laiosa MD, Svoboda KR, Udvadia AJ. Establishment of a murine culture system for modeling the temporal progression of cranial and trunk neural crest cell differentiation. Dis Model Mech 2018; 11:dmm.035097. [PMID: 30409814 PMCID: PMC6307900 DOI: 10.1242/dmm.035097] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 10/30/2018] [Indexed: 12/16/2022] Open
Abstract
The neural crest (NC) is a transient population of embryonic progenitors that are implicated in a diverse range of congenital birth defects and pediatric syndromes. The broad spectrum of NC-related disorders can be attributed to the wide variety of differentiated cell types arising from the NC. In vitro models of NC development provide a powerful platform for testing the relative contributions of intrinsic and extrinsic factors mediating NC differentiation under normal and pathogenic conditions. Although differentiation is a dynamic process that unfolds over time, currently, there is no well-defined chronology that characterizes the in vitro progression of NC differentiation towards specific cell fates. In this study, we have optimized culture conditions for expansion of primary murine NC cells that give rise to both ectodermal and mesoectodermal derivatives, even after multiple passages. Significantly, we have delineated highly reproducible timelines that include distinct intermediate stages for lineage-specific NC differentiation in vitro. In addition, isolating both cranial and trunk NC cells from the same embryos enabled us to make direct comparisons between the two cell populations over the course of differentiation. Our results define characteristic changes in cell morphology and behavior that track the temporal progression of NC cells as they differentiate along the neuronal, glial and chondrogenic lineages in vitro. These benchmarks constitute a chronological baseline for assessing how genetic or environmental disruptions may facilitate or impede NC differentiation. Introducing a temporal dimension substantially increases the power of this platform for screening drugs or chemicals for developmental toxicity or therapeutic potential.
This article has an associated First Person interview with the first author of the paper. Summary: A novel method for isolating and expanding primary neural crest cells, and establishment of reproducible temporal benchmarks of differentiation, provides a potential screening platform for developmental toxicity or therapeutic capacity.
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Affiliation(s)
- Maria R Replogle
- Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA
| | - Virinchipuram S Sreevidya
- Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA
| | - Vivian M Lee
- STEMCELL Technologies, Vancouver, BC V6A 1BC, Canada
| | - Michael D Laiosa
- Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA
| | - Kurt R Svoboda
- Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA
| | - Ava J Udvadia
- Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA
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26
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Le Douarin NM, Dupin E. The “beginnings” of the neural crest. Dev Biol 2018; 444 Suppl 1:S3-S13. [DOI: 10.1016/j.ydbio.2018.07.019] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 07/20/2018] [Accepted: 07/20/2018] [Indexed: 12/14/2022]
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27
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Dupin E, Calloni GW, Coelho-Aguiar JM, Le Douarin NM. The issue of the multipotency of the neural crest cells. Dev Biol 2018; 444 Suppl 1:S47-S59. [DOI: 10.1016/j.ydbio.2018.03.024] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 03/29/2018] [Accepted: 03/30/2018] [Indexed: 12/25/2022]
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28
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DeLaurier A. Evolution and development of the fish jaw skeleton. WILEY INTERDISCIPLINARY REVIEWS-DEVELOPMENTAL BIOLOGY 2018; 8:e337. [PMID: 30378758 DOI: 10.1002/wdev.337] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Revised: 09/25/2018] [Accepted: 09/27/2018] [Indexed: 12/18/2022]
Abstract
The evolution of the jaw represents a key innovation in driving the diversification of vertebrate body plans and behavior. The pharyngeal apparatus originated as gill bars separated by slits in chordate ancestors to vertebrates. Later, with the acquisition of neural crest, pharyngeal arches gave rise to branchial basket cartilages in jawless vertebrates (agnathans), and later bone and cartilage of the jaw, jaw support, and gills of jawed vertebrates (gnathostomes). Major events in the evolution of jaw structure from agnathans to gnathostomes include axial regionalization of pharyngeal elements and formation of a jaw joint. Hox genes specify the anterior-posterior identity of arches, and edn1, dlx, hand2, Jag1b-Notch2 signaling, and Nr2f factors specify dorsal-ventral identity. The formation of a jaw joint, an important step in the transition from an un-jointed pharynx in agnathans to a hinged jaw in gnathostomes involves interaction between nkx3.2, hand2, and barx1 factors. Major events in jaw patterning between fishes and reptiles include changes to elements of the second pharyngeal arch, including a loss of opercular and branchiostegal ray bones and transformation of the hyomandibula into the stapes. Further changes occurred between reptiles and mammals, including the transformation of the articular and quadrate elements of the jaw joint into the malleus and incus of the middle ear. Fossils of transitional jaw phenotypes can be analyzed from a developmental perspective, and there exists potential to use genetic manipulation techniques in extant taxa to test hypotheses about the evolution of jaw patterning in ancient vertebrates. This article is categorized under: Comparative Development and Evolution > Evolutionary Novelties Early Embryonic Development > Development to the Basic Body Plan Comparative Development and Evolution > Body Plan Evolution.
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Affiliation(s)
- April DeLaurier
- Department of Biology and Geology, University of South Carolina Aiken, Aiken, South Carolina
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29
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Sakuma R, Takahashi A, Nakano-Doi A, Sawada R, Kamachi S, Beppu M, Takagi T, Yoshimura S, Matsuyama T, Nakagomi T. Comparative Characterization of Ischemia-Induced Brain Multipotent Stem Cells with Mesenchymal Stem Cells: Similarities and Differences. Stem Cells Dev 2018; 27:1322-1338. [PMID: 29999479 DOI: 10.1089/scd.2018.0075] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent stem cells localized to the perivascular regions of various organs, including bone marrow (BM). While MSC transplantation represents a promising stem cell-based therapy for ischemic stroke, increasing evidence indicates that exogenously administered MSCs rarely accumulate in the injured central nervous system (CNS). Therefore, compared with MSCs, regionally derived brain multipotent stem cells may be a superior source to elicit regeneration of the CNS following ischemic injury. We previously identified ischemia-induced multipotent stem cells (iSCs) as likely originating from brain pericytes/perivascular cells (PCs) within poststroke regions. However, detailed characteristics of iSCs and their comparison with MSCs remains to be investigated. In the present study, we compared iSCs with BM-derived MSCs, with a focus on the stemness and neuron-generating activity of each cell type. From our results, stem and undifferentiated cell markers, including c-myc and Klf4, were found to be expressed in iSCs and BM-MSCs. In addition, both cell types exhibited the ability to differentiate into mesoderm lineages, including as osteoblasts, adipocytes, and chondrocytes. However, compared with BM-MSCs, high expression of neural stem cell markers, including nestin and Sox2, were found in iSCs. In addition, iSCs, but not BM-MSCs, formed neurosphere-like cell clusters that differentiated into functional neurons. These results demonstrate that iSCs are likely multipotent stem cells with the ability to differentiate into not only mesoderm, but also neural, lineages. Collectively, our novel findings suggest that locally induced iSCs may contribute to CNS repair by producing neuronal cells following ischemic stroke.
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Affiliation(s)
- Rika Sakuma
- 1 Institute for Advanced Medical Sciences , Hyogo College of Medicine, Nishinomiya, Japan
| | - Ai Takahashi
- 1 Institute for Advanced Medical Sciences , Hyogo College of Medicine, Nishinomiya, Japan .,2 Graduate School of Science and Technology, Kwansei Gakuin University , Sanda, Japan
| | - Akiko Nakano-Doi
- 1 Institute for Advanced Medical Sciences , Hyogo College of Medicine, Nishinomiya, Japan .,3 Department of Therapeutic Progress in Brain Diseases, Hyogo College of Medicine , Nishinomiya, Japan
| | - Rikako Sawada
- 1 Institute for Advanced Medical Sciences , Hyogo College of Medicine, Nishinomiya, Japan .,2 Graduate School of Science and Technology, Kwansei Gakuin University , Sanda, Japan
| | - Saeko Kamachi
- 3 Department of Therapeutic Progress in Brain Diseases, Hyogo College of Medicine , Nishinomiya, Japan
| | - Mikiya Beppu
- 4 Department of Neurosurgery, Hyogo College of Medicine , Nishinomiya, Japan
| | - Toshinori Takagi
- 4 Department of Neurosurgery, Hyogo College of Medicine , Nishinomiya, Japan
| | - Shinichi Yoshimura
- 4 Department of Neurosurgery, Hyogo College of Medicine , Nishinomiya, Japan
| | - Tomohiro Matsuyama
- 3 Department of Therapeutic Progress in Brain Diseases, Hyogo College of Medicine , Nishinomiya, Japan
| | - Takayuki Nakagomi
- 1 Institute for Advanced Medical Sciences , Hyogo College of Medicine, Nishinomiya, Japan .,3 Department of Therapeutic Progress in Brain Diseases, Hyogo College of Medicine , Nishinomiya, Japan
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30
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Latin American contributions to the neural crest field. Mech Dev 2018; 153:17-29. [PMID: 30081090 DOI: 10.1016/j.mod.2018.07.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Revised: 07/15/2018] [Accepted: 07/26/2018] [Indexed: 11/21/2022]
Abstract
The neural crest (NC) is one of the most fascinating structures during embryonic development. Unique to vertebrate embryos, these cells give rise to important components of the craniofacial skeleton, such as the jaws and skull, as well as melanocytes and ganglia of the peripheral nervous system. Worldwide, several groups have been studying NC development and specifically in the Latin America (LA) they have been growing in numbers since the 1990s. It is important for the world to recognize the contributions of LA researchers on the knowledge of NC development, as it can stimulate networking and improvement in the field. We developed a database of LA publications on NC development using ORCID and PUBMED as search engines. We thoroughly describe all of the contributions from LA, collected in five major topics on NC development mechanisms: i) induction and specification; ii) migration; iii) differentiation; iv) adult NC; and, v) neurocristopathies. Further analysis was done to correlate each LA country with topics and animal models, and to access collaboration between LA countries. We observed that some LA countries have made important contributions to the comprehension of NC development. Interestingly, some LA countries have a topic and an animal model as their strength; in addition, collaboration between LA countries is almost inexistent. This review will help LA NC research to be acknowledged, and to facilitate networking between students and researchers worldwide.
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31
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da Costa MC, Trentin AG, Calloni GW. FGF8 and Shh promote the survival and maintenance of multipotent neural crest progenitors. Mech Dev 2018; 154:251-258. [PMID: 30075227 DOI: 10.1016/j.mod.2018.07.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Revised: 07/30/2018] [Accepted: 07/31/2018] [Indexed: 02/07/2023]
Abstract
The developmental mechanisms that control the building of the complex head of vertebrates and particularly, facial skeletogenesis, remain poorly known. Progenitor cells derived from the embryonic neural crest (NC) are the major constituents and players of facial tissue development. Deciphering the cellular and molecular machinery that controls NC cell (NCC) differentiation into bone, cartilage, fat and other mesenchymal tissues, is thus a main issue for understanding vertebrate facial variations. In this work, we investigated the effects of fibroblast growth factor 8 (FGF8) and Sonic Hedgehog (Shh), two signaling molecules essential for craniofacial development, on the in vitro differentiation and multipotentiality of mesencephalic NCCs (MNCCs) isolated from the quail embryo. Comparison of distinct temporal treatments with FGF8 and/or Shh showed that both promoted chondrogenesis of MNCCs by increasing the amount and size of cartilage nodules. Higher rates of chondrogenesis were observed when MNCCs were treated with FGF8 during the migration phase, thus mimicking the in vivo exposure of migrating NCCs to FGF8 secreted by the isthmic brain signaling center. An in vitro cell cloning assay revealed that, after concomitant treatment with FGF8 and Shh, about 80% of NC progenitors displayed chondrogenic potential, while in untreated cultures, only 18% exhibited this potential. In addition, colony analysis showed for the first time the existence of a highly multipotent progenitor able to clonally give rise to adipocytes in addition to other cephalic NC phenotypes (i.e. glial cells, neurons, melanocytes, smooth muscle cells and chondrocytes) (GNMFCA progenitor). This progenitor was observed only when clonal cultures were treated with both FGF8 and Shh. Several other types of multipotent cells, which generated four, five or six distinct phenotypes, accounted for 55% of the progenitors in FGF8 and Shh treated cultures, versus 13,5% in the untreated ones. Together, these data reveal an essential role for both FGF8 and Shh together in maintenance of MNCC multipotentiality by favoring the development of NC progenitors endowed with a broad array of mesectodermal potentials.
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Affiliation(s)
- Meline Coelho da Costa
- Laboratório de Plasticidade e Diferenciação de Células da Crista Neural, Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900 Florianópolis, SC, Brazil; Laboratório de Células Tronco e Regeneração Tecidual, Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900 Florianópolis, SC, Brazil
| | - Andréa Gonçalves Trentin
- Laboratório de Células Tronco e Regeneração Tecidual, Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900 Florianópolis, SC, Brazil
| | - Giordano Wosgrau Calloni
- Laboratório de Plasticidade e Diferenciação de Células da Crista Neural, Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900 Florianópolis, SC, Brazil.
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32
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Kundu RV, Mhlaba JM, Rangel SM, Le Poole IC. The convergence theory for vitiligo: A reappraisal. Exp Dermatol 2018; 28:647-655. [PMID: 29704874 DOI: 10.1111/exd.13677] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/18/2018] [Indexed: 12/15/2022]
Abstract
Vitiligo is characterized by progressive loss of skin pigmentation. The search for aetiologic factors has led to the biochemical, the neurologic and the autoimmune theory. The convergence theory was then proposed several years ago to incorporate existing theories of vitiligo development into a single overview of vitiligo aetiology. The viewpoint that vitiligo is not caused only by predisposing mutations, or only by melanocytes responding to chemical/radiation exposure, or only by hyperreactive T cells, but rather results from a combination of aetiologic factors that impact melanocyte viability, has certainly stood the test of time. New findings have since informed the description of progressive depigmentation. Understanding the relative importance of such aetiologic factors combined with a careful selection of the most targetable pathways will continue to drive the next phase in vitiligo research: the development of effective therapeutics. In that arena, it is likewise important to acknowledge that pathways affected in some patients may not be altered in others. Taken together, the convergence theory continues to provide a comprehensive viewpoint of vitiligo aetiology. The theory serves to intertwine aetiologic pathways and will help to define pathways amenable to disease intervention in individual patients.
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Affiliation(s)
- Roopal V Kundu
- Department of Dermatology, Northwestern University, Chicago, IL, USA
| | - Julia M Mhlaba
- Department of Dermatology, Northwestern University, Chicago, IL, USA
| | | | - I Caroline Le Poole
- Department of Dermatology, Northwestern University, Chicago, IL, USA.,Department of Microbiology and Immunology, Northwestern University, Chicago, IL, USA
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33
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Bagher Z, Kamrava SK, Alizadeh R, Farhadi M, Absalan M, Falah M, Faghihi F, Zare-Sadeghi A, Komeili A. Differentiation of neural crest stem cells from nasal mucosa into motor neuron-like cells. J Chem Neuroanat 2018; 92:35-40. [PMID: 29807106 DOI: 10.1016/j.jchemneu.2018.05.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 04/23/2018] [Accepted: 05/24/2018] [Indexed: 12/22/2022]
Abstract
Cell transplantation is a potential therapeutic approach for repairing neuropathological and neurodegenerative disorders of central nervous system by replacing the degenerated cells with new ones. Among a variety of stem cell candidates to provide these new cells, olfactory ectomesenchymal stem cells (OE-MSCs) have attracted a great attention due to their neural crest origin, easy harvest, high proliferation, and autologous transplantation. Since there is no report on differentiation potential of these cells into motor neuron-like cells, we evaluated this potential using Real-time PCR, flowcytometry and immunocytochemistry after the treatment with differentiation cocktail containing retinoic acid and Sonic Hedgehog. Immunocytochemistry staining of the isolated OE-MSCs demonstrated their capability to express nestin and vimentin, as the two markers of primitive neuroectoderm. The motor neuron differentiation of OE-MSCs resulted in changing their morphology into bipolar cells with high expression of motor neuron markers of ChAT, Hb-9 and Islet-1 at the level of mRNA and protein. Consequently, we believe that the OE-MSCs have great potential to differentiate into motor neuron-like cells and can be an ideal stem cell source for the treatment of motor neuron-related disorders of central nervous system.
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Affiliation(s)
- Zohreh Bagher
- ENT and Head & Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Seyed Kamran Kamrava
- ENT and Head & Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Rafieh Alizadeh
- ENT and Head & Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Mohammad Farhadi
- ENT and Head & Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Moloud Absalan
- Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Falah
- ENT and Head & Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Faezeh Faghihi
- Cellular and molecular research center, Iran university of Medical Sciences, Tehran, Iran
| | - Arash Zare-Sadeghi
- Skull Base Research Center, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Ali Komeili
- Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran.
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34
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The neural crest and evolution of the head/trunk interface in vertebrates. Dev Biol 2018; 444 Suppl 1:S60-S66. [PMID: 29408469 DOI: 10.1016/j.ydbio.2018.01.017] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Revised: 01/24/2018] [Accepted: 01/24/2018] [Indexed: 12/31/2022]
Abstract
The migration and distribution patterns of neural crest (NC) cells reflect the distinct embryonic environments of the head and trunk: cephalic NC cells migrate predominantly along the dorsolateral pathway to populate the craniofacial and pharyngeal regions, whereas trunk crest cells migrate along the ventrolateral pathways to form the dorsal root ganglia. These two patterns thus reflect the branchiomeric and somitomeric architecture, respectively, of the vertebrate body plan. The so-called vagal NC occupies a postotic, intermediate level between the head and trunk NC. This level of NC gives rise to both trunk- and cephalic-type (circumpharyngeal) NC cells. The anatomical pattern of the amphioxus, a basal chordate, suggests that somites and pharyngeal gills coexist along an extensive length of the body axis, indicating that the embryonic environment is similar to that of vertebrate vagal NC cells and may have been ancestral for vertebrates. The amniote-like condition in which the cephalic and trunk domains are distinctly separated would have been brought about, in part, by anteroposterior reduction of the pharyngeal domain.
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Lignell A, Kerosuo L, Streichan SJ, Cai L, Bronner ME. Identification of a neural crest stem cell niche by Spatial Genomic Analysis. Nat Commun 2017; 8:1830. [PMID: 29184067 PMCID: PMC5705662 DOI: 10.1038/s41467-017-01561-w] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Accepted: 09/27/2017] [Indexed: 12/29/2022] Open
Abstract
The neural crest is an embryonic population of multipotent stem cells that form numerous defining features of vertebrates. Due to lack of reliable techniques to perform transcriptional profiling in intact tissues, it remains controversial whether the neural crest is a heterogeneous or homogeneous population. By coupling multiplex single molecule fluorescence in situ hybridization with machine learning algorithm based cell segmentation, we examine expression of 35 genes at single cell resolution in vivo. Unbiased hierarchical clustering reveals five spatially distinct subpopulations within the chick dorsal neural tube. Here we identify a neural crest stem cell niche that centers around the dorsal midline with high expression of neural crest genes, pluripotency factors, and lineage markers. Interestingly, neural and neural crest stem cells express distinct pluripotency signatures. This Spatial Genomic Analysis toolkit provides a straightforward approach to study quantitative multiplex gene expression in numerous biological systems, while offering insights into gene regulatory networks via synexpression analysis.
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Affiliation(s)
- Antti Lignell
- Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA
| | - Laura Kerosuo
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA
| | - Sebastian J Streichan
- Biomolecular Science and Engineering, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA
| | - Long Cai
- Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
| | - Marianne E Bronner
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
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Münst S, Koch P, Kesavan J, Alexander-Mays M, Münst B, Blaess S, Brüstle O. In vitro segregation and isolation of human pluripotent stem cell-derived neural crest cells. Methods 2017; 133:65-80. [PMID: 29037816 DOI: 10.1016/j.ymeth.2017.09.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 09/24/2017] [Accepted: 09/27/2017] [Indexed: 01/17/2023] Open
Abstract
The neural crest (NC) is a transient embryonic cell population with remarkable characteristics. After delaminating from the neural tube, NC cells (NCCs) migrate extensively, populate nearly every tissue of the body and differentiate into highly diverse cell types such as peripheral neurons and glia, but also mesenchymal cells including chondrocytes, osteocytes, and adipocytes. While the NC has been extensively studied in several animal models, little is known about human NC development. A number of methods have been established to derive NCCs in vitro from human pluripotent stem cells (hPSC). Typically, these protocols comprise several cell culture steps to enrich for NCCs in the neural derivatives of the differentiating hPSCs. Here we report on a remarkable and hitherto unnoticed in vitro segregation phenomenon that enables direct extraction of virtually pure NCCs during the earliest stages of hPSC differentiation. Upon aggregation to embryoid bodies (EB) and replating, differentiating hPSCs give rise to a population of NCCs, which spontaneously segregate from the EB outgrowth to form conspicuous, macroscopically visible atoll-shaped clusters in the periphery of the EB outgrowth. Isolation of these NC clusters yields p75NTR(+)/SOXE(+) NCCs, which differentiate to peripheral neurons and glia as well as mesenchymal derivatives. Our data indicate that differentiating hPSC cultures recapitulate, in a simplified manner, the physical segregation of central nervous system (CNS) tissue and NCCs. This phenomenon may be exploited for NCC purification and for studying segregation and differentiation processes observed during early human NC development in vitro.
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Affiliation(s)
- Sabine Münst
- Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany
| | - Philipp Koch
- Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany
| | - Jaideep Kesavan
- Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany
| | - Michael Alexander-Mays
- Institute of Human Genetics, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany
| | - Bernhard Münst
- Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany
| | - Sandra Blaess
- Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany
| | - Oliver Brüstle
- Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany.
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Fonseca BF, Couly G, Dupin E. Respective contribution of the cephalic neural crest and mesoderm to SIX1-expressing head territories in the avian embryo. BMC DEVELOPMENTAL BIOLOGY 2017; 17:13. [PMID: 29017464 PMCID: PMC5634862 DOI: 10.1186/s12861-017-0155-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Accepted: 10/01/2017] [Indexed: 12/13/2022]
Abstract
Background Vertebrate head development depends on a series of interactions between many cell populations of distinct embryological origins. Cranial mesenchymal tissues have a dual embryonic source: - the neural crest (NC), which generates most of craniofacial skeleton, dermis, pericytes, fat cells, and tenocytes; and - the mesoderm, which yields muscles, blood vessel endothelia and some posterior cranial bones. The molecular players that orchestrate co-development of cephalic NC and mesodermal cells to properly construct the head of vertebrates remain poorly understood. In this regard, Six1 gene, a vertebrate homolog of Drosophila Sine Oculis, is known to be required for development of ear, nose, tongue and cranial skeleton. However, the embryonic origin and fate of Six1-expressing cells have remained unclear. In this work, we addressed these issues in the avian embryo model by using quail-chick chimeras, cephalic NC cultures and immunostaining for SIX1. Results Our data show that, at early NC migration stages, SIX1 is expressed by mesodermal cells but excluded from the NC cells (NCC). Then, SIX1 becomes widely expressed in NCC that colonize the pre-otic mesenchyme. In contrast, in the branchial arches (BAs), SIX1 is present only in mesodermal cells that give rise to jaw muscles. At later developmental stages, the distribution of SIX1-expressing cells in mesoderm-derived tissues is consistent with a possible role of this factor in the myogenic program of all types of head muscles, including pharyngeal, extraocular and tongue muscles. In NC derivatives, SIX1 is notably expressed in perichondrium and chondrocytes of the nasal septum and in the sclera, although other facial cartilages such as Meckel’s were negative at the stages considered. Moreover, in cephalic NC cultures, chondrocytes and myofibroblasts, not the neural and melanocytic cells express SIX1. Conclusion The present results point to a dynamic tissue-specific expression of SIX1 in a variety of cephalic NC- and mesoderm-derived cell types and tissues, opening the way for further analysis of Six1 function in the coordinated development of these two cellular populations during vertebrate head formation. Electronic supplementary material The online version of this article (10.1186/s12861-017-0155-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Barbara F Fonseca
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012, Paris, France
| | - Gérard Couly
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012, Paris, France.,Université Paris Descartes, Institut de la Bouche et du Visage de l'Enfant, Hôpital Universitaire Necker, 149, rue de Sèvres, 75015, Paris, France
| | - Elisabeth Dupin
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012, Paris, France.
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Novel Regenerative Therapies Based on Regionally Induced Multipotent Stem Cells in Post-Stroke Brains: Their Origin, Characterization, and Perspective. Transl Stroke Res 2017; 8:515-528. [PMID: 28744717 DOI: 10.1007/s12975-017-0556-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 07/07/2017] [Accepted: 07/18/2017] [Indexed: 12/16/2022]
Abstract
Brain injuries such as ischemic stroke cause severe neural loss. Until recently, it was believed that post-ischemic areas mainly contain necrotic tissue and inflammatory cells. However, using a mouse model of cerebral infarction, we demonstrated that stem cells develop within ischemic areas. Ischemia-induced stem cells can function as neural progenitors; thus, we initially named them injury/ischemia-induced neural stem/progenitor cells (iNSPCs). However, because they differentiate into more than neural lineages, we now refer to them as ischemia-induced multipotent stem cells (iSCs). Very recently, we showed that putative iNSPCs/iSCs are present within post-stroke areas in human brains. Because iNSPCs/iSCs isolated from mouse and human ischemic tissues can differentiate into neuronal lineages in vitro, it is possible that a clearer understanding of iNSPC/iSC profiles and the molecules that regulate iNSPC/iSC fate (e.g., proliferation, differentiation, and survival) would make it possible to perform neural regeneration/repair in patients following stroke. In this article, we introduce the origin and traits of iNSPCs/iSCs based on our reports and recent viewpoints. We also discuss their possible contribution to neurogenesis through endogenous and exogenous iNSPC/iSC therapies following ischemic stroke.
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Zurkirchen L, Sommer L. Quo vadis: tracing the fate of neural crest cells. Curr Opin Neurobiol 2017; 47:16-23. [PMID: 28753439 DOI: 10.1016/j.conb.2017.07.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 06/30/2017] [Accepted: 07/03/2017] [Indexed: 12/16/2022]
Abstract
The neural crest is a transient structure in vertebrate embryos that produces migratory cells with an astonishing developmental potential. While neural crest fate maps have originally been established through interspecies transplantation assays, dye labeling, and retroviral infection, more recent methods rely on approaches involving transgenesis and genome editing. These technologies allowed the identification of minor neural crest-derived cell populations in tissues of non-neural crest origin. Furthermore, in vivo multipotency at the single cell level and stage-dependent fate acquisitions were demonstrated using genetic technologies. Finally, recent reports indicate that neural crest-derived cells become activated in response to injury to secrete factors supporting tissue repair. Thus, neural crest-derived cells apparently contribute to tissue formation and regeneration by cell autonomous and non-autonomous mechanisms.
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Affiliation(s)
- Luis Zurkirchen
- Stem Cell Biology, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
| | - Lukas Sommer
- Stem Cell Biology, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
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Tatebayashi K, Tanaka Y, Nakano-Doi A, Sakuma R, Kamachi S, Shirakawa M, Uchida K, Kageyama H, Takagi T, Yoshimura S, Matsuyama T, Nakagomi T. Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke. Stem Cells Dev 2017; 26:787-797. [PMID: 28323540 PMCID: PMC5466056 DOI: 10.1089/scd.2016.0334] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.
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Affiliation(s)
- Kotaro Tatebayashi
- 1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Yasue Tanaka
- 1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan .,2 Institute for Advanced Medical Sciences , Hyogo College of Medicine, Nishinomiya, Japan
| | - Akiko Nakano-Doi
- 2 Institute for Advanced Medical Sciences , Hyogo College of Medicine, Nishinomiya, Japan
| | - Rika Sakuma
- 2 Institute for Advanced Medical Sciences , Hyogo College of Medicine, Nishinomiya, Japan
| | - Saeko Kamachi
- 2 Institute for Advanced Medical Sciences , Hyogo College of Medicine, Nishinomiya, Japan
| | - Manabu Shirakawa
- 1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Kazutaka Uchida
- 1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Hiroto Kageyama
- 1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Toshinori Takagi
- 1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Shinichi Yoshimura
- 1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Tomohiro Matsuyama
- 2 Institute for Advanced Medical Sciences , Hyogo College of Medicine, Nishinomiya, Japan
| | - Takayuki Nakagomi
- 2 Institute for Advanced Medical Sciences , Hyogo College of Medicine, Nishinomiya, Japan
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Liu JA, Cheung M. Neural crest stem cells and their potential therapeutic applications. Dev Biol 2016; 419:199-216. [PMID: 27640086 DOI: 10.1016/j.ydbio.2016.09.006] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Revised: 09/07/2016] [Accepted: 09/07/2016] [Indexed: 12/13/2022]
Abstract
The neural crest (NC) is a remarkable transient structure generated during early vertebrate development. The neural crest progenitors have extensive migratory capacity and multipotency, harboring stem cell-like characteristics such as self-renewal. They can differentiate into a variety of cell types from craniofacial skeletal tissues to the trunk peripheral nervous system (PNS). Multiple regulators such as signaling factors, transcription factors, and migration machinery components are expressed at different stages of NC development. Gain- and loss-of-function studies in various vertebrate species revealed epistatic relationships of these molecules that could be assembled into a gene regulatory network defining the processes of NC induction, specification, migration, and differentiation. These basic developmental studies led to the subsequent establishment and molecular validation of neural crest stem cells (NCSCs) derived by various strategies. We provide here an overview of the isolation and characterization of NCSCs from embryonic, fetal, and adult tissues; the experimental strategies for the derivation of NCSCs from embryonic stem cells, induced pluripotent stem cells, and skin fibroblasts; and recent developments in the use of patient-derived NCSCs for modeling and treating neurocristopathies. We discuss future research on further refinement of the culture conditions required for the differentiation of pluripotent stem cells into axial-specific NC progenitors and their derivatives, developing non-viral approaches for the generation of induced NC cells (NCCs), and using a genomic editing approach to correct genetic mutations in patient-derived NCSCs for transplantation therapy. These future endeavors should facilitate the therapeutic applications of NCSCs in the clinical setting.
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Affiliation(s)
- Jessica Aijia Liu
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Martin Cheung
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
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Agarwalla PK, Koch MJ, Mordes DA, Codd PJ, Coumans JV. Pigmented Lesions of the Nervous System and the Neural Crest: Lessons From Embryology. Neurosurgery 2016; 78:142-55. [PMID: 26355366 DOI: 10.1227/neu.0000000000001010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Neurosurgeons encounter a number of pigmented tumors of the central nervous system in a variety of locations, including primary central nervous system melanoma, blue nevus of the spinal cord, and melanotic schwannoma. When examined through the lens of embryology, pigmented lesions share a unifying connection: They occur in structures that are neural crest cell derivatives. Here, we review the important progress made in the embryology of neural crest cells, present 3 cases of pigmented tumors of the nervous system, and discuss these clinical entities in the context of the development of melanoblasts. Pigmented lesions of the nervous system arise along neural crest cell migration routes and from neural crest-derived precursors. Awareness of the evolutionary clues of vertebrate pigmentation by the neurosurgical and neuro-oncological community at large is valuable for identifying pathogenic or therapeutic targets and for designing future research on nervous system pigmented lesions. When encountering such a lesion, clinicians should be aware of the embryological basis to direct additional evaluation, including genetic testing, and to work with the scientific community in better understanding these lesions and their relationship to neural crest developmental biology.
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Affiliation(s)
- Pankaj K Agarwalla
- Departments of *Neurosurgery and‡Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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Namkoong B, Güven S, Ramesan S, Liaudanskaya V, Abzhanov A, Demirci U. Recapitulating cranial osteogenesis with neural crest cells in 3-D microenvironments. Acta Biomater 2016; 31:301-311. [PMID: 26675129 DOI: 10.1016/j.actbio.2015.12.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 11/11/2015] [Accepted: 12/02/2015] [Indexed: 01/20/2023]
Abstract
The experimental systems that recapitulate the complexity of native tissues and enable precise control over the microenvironment are becoming essential for the pre-clinical tests of therapeutics and tissue engineering. Here, we described a strategy to develop an in vitro platform to study the developmental biology of craniofacial osteogenesis. In this study, we directly osteo-differentiated cranial neural crest cells (CNCCs) in a 3-D in vitro bioengineered microenvironment. Cells were encapsulated in the gelatin-based photo-crosslinkable hydrogel and cultured up to three weeks. We demonstrated that this platform allows efficient differentiation of p75 positive CNCCs to cells expressing osteogenic markers corresponding to the sequential developmental phases of intramembranous ossification. During the course of culture, we observed a decrease in the expression of early osteogenic marker Runx2, while the other mature osteoblast and osteocyte markers such as Osterix, Osteocalcin, Osteopontin and Bone sialoprotein increased. We analyzed the ossification of the secreted matrix with alkaline phosphatase and quantified the newly secreted hydroxyapatite. The Field Emission Scanning Electron Microscope (FESEM) images of the bioengineered hydrogel constructs revealed the native-like osteocytes, mature osteoblasts, and cranial bone tissue morphologies with canaliculus-like intercellular connections. This platform provides a broadly applicable model system to potentially study diseases involving primarily embryonic craniofacial bone disorders, where direct diagnosis and adequate animal disease models are limited.
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Affiliation(s)
- Bumjin Namkoong
- Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
| | - Sinan Güven
- Demirci BAMM Labs, Canary Center at Stanford for Early Cancer Detection, Department of Radiology, Department of Electrical Engineering (By courtesy), Stanford School of Medicine, Palo Alto, CA 94304, USA; Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Balcova, 35350 Izmir, Turkey
| | - Shwathy Ramesan
- Demirci BAMM Labs, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Volha Liaudanskaya
- Demirci BAMM Labs, Canary Center at Stanford for Early Cancer Detection, Department of Radiology, Department of Electrical Engineering (By courtesy), Stanford School of Medicine, Palo Alto, CA 94304, USA
| | - Arhat Abzhanov
- Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Current address: Department of Life Sciences, Imperial College London, Silwood Park Campus Buckhurst Road, Ascot, Berkshire SL5 7PY, United Kingdom; Current address: Natural History Museum, Cromwell Road, London SW7 5BD, United Kingdom.
| | - Utkan Demirci
- Demirci BAMM Labs, Canary Center at Stanford for Early Cancer Detection, Department of Radiology, Department of Electrical Engineering (By courtesy), Stanford School of Medicine, Palo Alto, CA 94304, USA; Demirci BAMM Labs, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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Le Douarin NM, Dupin E. The Pluripotency of Neural Crest Cells and Their Role in Brain Development. Curr Top Dev Biol 2016; 116:659-78. [PMID: 26970647 DOI: 10.1016/bs.ctdb.2015.10.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The neural crest (NC) is, in the Chordate phylum, an innovation of vertebrates, which exhibits several original characteristics: its component cells are pluripotent and give rise to both ectodermal and mesodermal cell types. Moreover, during the early stages of neurogenesis, the NC cells exert a paracrine stimulating effect on the development of the preotic brain.
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Affiliation(s)
- Nicole M Le Douarin
- Collège de France, 3 rue d'Ulm, Paris, France; INSERM U968, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 968, Institut de la Vision, Paris, France; CNRS, UMR 7210, Paris, France.
| | - Elisabeth Dupin
- INSERM U968, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 968, Institut de la Vision, Paris, France; CNRS, UMR 7210, Paris, France
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Toledo RA, Qin Y, Cheng ZM, Gao Q, Iwata S, Silva GM, Prasad ML, Ocal IT, Rao S, Aronin N, Barontini M, Bruder J, Reddick RL, Chen Y, Aguiar RCT, Dahia PLM. Recurrent Mutations of Chromatin-Remodeling Genes and Kinase Receptors in Pheochromocytomas and Paragangliomas. Clin Cancer Res 2015; 22:2301-10. [PMID: 26700204 DOI: 10.1158/1078-0432.ccr-15-1841] [Citation(s) in RCA: 104] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 12/02/2015] [Indexed: 02/06/2023]
Abstract
PURPOSE Pheochromocytomas and paragangliomas (PPGL) are genetically heterogeneous tumors of neural crest origin, but the molecular basis of most PPGLs is unknown. EXPERIMENTAL DESIGN We performed exome or transcriptome sequencing of 43 samples from 41 patients. A validation set of 136 PPGLs was used for amplicon-specific resequencing. In addition, a subset of these tumors was subjected to microarray-based transcription, protein expression, and histone methylation analysis by Western blotting or immunohistochemistry. In vitro analysis of mutants was performed in cell lines. RESULTS We detected mutations in chromatin-remodeling genes, including histone-methyltransferases, histone-demethylases, and histones in 11 samples from 8 patients (20%). In particular, we characterized a new cancer syndrome involving PPGLs and giant cell tumors of bone (GCT) caused by a postzygotic G34W mutation of the histone 3.3 gene, H3F3A Furthermore, mutations in kinase genes were detected in samples from 15 patients (37%). Among those, a novel germline kinase domain mutation of MERTK detected in a patient with PPGL and medullary thyroid carcinoma was found to activate signaling downstream of this receptor. Recurrent germline and somatic mutations were also detected in MET, including a familial case and sporadic PPGLs. Importantly, in each of these three genes, mutations were also detected in the validation group. In addition, a somatic oncogenic hotspot FGFR1 mutation was found in a sporadic tumor. CONCLUSIONS This study implicates chromatin-remodeling and kinase variants as frequent genetic events in PPGLs, many of which have no other known germline driver mutation. MERTK, MET, and H3F3A emerge as novel PPGL susceptibility genes. Clin Cancer Res; 22(9); 2301-10. ©2015 AACR.
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Affiliation(s)
- Rodrigo A Toledo
- Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas
| | - Yuejuan Qin
- Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas
| | - Zi-Ming Cheng
- Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas
| | - Qing Gao
- Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas
| | - Shintaro Iwata
- Division of Orthopedic Surgery, Chiba Cancer Center, Chiba, Japan
| | - Gustavo M Silva
- Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York
| | - Manju L Prasad
- Department of Pathology, Yale University, New Haven, Connecticut
| | - I Tolgay Ocal
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, Arizona
| | - Sarika Rao
- Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
| | - Neil Aronin
- Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
| | - Marta Barontini
- Center for Endocrinological Investigations (CEDIE), Buenos Aires, Argentina
| | - Jan Bruder
- Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas
| | - Robert L Reddick
- Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas
| | - Yidong Chen
- Department of Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, Texas
| | - Ricardo C T Aguiar
- Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas. South Texas Veterans Health Care System, Audie Murphy VA Hospital, San Antonio, Texas
| | - Patricia L M Dahia
- Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Cancer Therapy and Research Center (CTRC), University of Texas Health Science Center at San Antonio, San Antonio, Texas.
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Kerosuo L, Nie S, Bajpai R, Bronner ME. Crestospheres: Long-Term Maintenance of Multipotent, Premigratory Neural Crest Stem Cells. Stem Cell Reports 2015; 5:499-507. [PMID: 26441305 PMCID: PMC4625028 DOI: 10.1016/j.stemcr.2015.08.017] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Revised: 08/27/2015] [Accepted: 08/28/2015] [Indexed: 01/12/2023] Open
Abstract
Premigratory neural crest cells comprise a transient, embryonic population that arises within the CNS, but subsequently migrates away and differentiates into many derivatives. Previously, premigratory neural crest could not be maintained in a multipotent, adhesive state without spontaneous differentiation. Here, we report conditions that enable maintenance of neuroepithelial “crestospheres” that self-renew and retain multipotency for weeks. Moreover, under differentiation conditions, these cells can form multiple derivatives in vitro and in vivo after transplantation into chick embryos. Similarly, human embryonic stem cells directed to a neural crest fate can be maintained as crestospheres and subsequently differentiated into several derivatives. By devising conditions that maintain the premigratory state in vitro, these results demonstrate that neuroepithelial neural crest precursors are capable of long-term self-renewal. This approach will help uncover mechanisms underlying their developmental potential, differentiation and, together with the induced pluripotent stem cell techniques, the pathology of human neurocristopathies.
Long-term maintenance of premigratory chick neural crest cells as crestospheres A self-renewing population of multipotent neuroepithelial neural crest stem cells Crestospheres differentiate into neural crest derivatives in vitro and in vivo Long-term maintenance of human ESC-derived crestospheres for several weeks
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Affiliation(s)
- Laura Kerosuo
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
| | - Shuyi Nie
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
| | - Ruchi Bajpai
- Center for Craniofacial Molecular Biology and Department of Biochemistry, University of Southern California, Los Angeles, CA 90089, USA
| | - Marianne E Bronner
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
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Nakagomi T, Nakano-Doi A, Kawamura M, Matsuyama T. Do Vascular Pericytes Contribute to Neurovasculogenesis in the Central Nervous System as Multipotent Vascular Stem Cells? Stem Cells Dev 2015; 24:1730-9. [PMID: 25900222 DOI: 10.1089/scd.2015.0039] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Increasing evidence suggests that multipotent stem cells are harbored within a vascular niche inside various organs. Although a precise phenotype of resident vascular stem cells (VSCs) that can function as multipotent stem cells remains unclear, accumulating evidence shows that multipotent VSCs are likely vascular pericytes (PCs) that localize within blood vessels. These PCs are multipotent, possessing the ability to differentiate into various cell types, including vascular lineage cells. In addition, brain PCs are unique: They are derived from neural crest and can differentiate into neural lineage cells. Because PCs in the central nervous system (CNS) can contribute to both neurogenesis and vasculogenesis, they may mediate the reparative process of neurovascular units that are constructed by neural and vascular cells. Here, we describe the activity of PCs when viewed as multipotent VSCs, primarily regarding their neurogenic and vasculogenic potential in the CNS. We also discuss similarities between PCs and other candidates for multipotent VSCs, including perivascular mesenchymal stem cells, neural crest-derived stem cells, adventitial progenitor cells, and adipose-derived stem cells.
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Affiliation(s)
- Takayuki Nakagomi
- 1 Institute for Advanced Medical Sciences, Hyogo College of Medicine , Hyogo, Japan
| | - Akiko Nakano-Doi
- 1 Institute for Advanced Medical Sciences, Hyogo College of Medicine , Hyogo, Japan
| | - Miki Kawamura
- 1 Institute for Advanced Medical Sciences, Hyogo College of Medicine , Hyogo, Japan .,2 Department of Neurology, Osaka University Graduate School of Medicine , Osaka, Japan
| | - Tomohiro Matsuyama
- 1 Institute for Advanced Medical Sciences, Hyogo College of Medicine , Hyogo, Japan
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Evolution of vertebrates as viewed from the crest. Nature 2015; 520:474-482. [PMID: 25903629 DOI: 10.1038/nature14436] [Citation(s) in RCA: 155] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Accepted: 02/05/2015] [Indexed: 12/21/2022]
Abstract
The origin of vertebrates was accompanied by the advent of a novel cell type: the neural crest. Emerging from the central nervous system, these cells migrate to diverse locations and differentiate into numerous derivatives. By coupling morphological and gene regulatory information from vertebrates and other chordates, we describe how addition of the neural-crest-specification program may have enabled cells at the neural plate border to acquire multipotency and migratory ability. Analysis of the topology of the neural crest gene regulatory network can serve as a useful template for understanding vertebrate evolution, including elaboration of neural crest derivatives.
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Shyamala K, Yanduri S, Girish HC, Murgod S. Neural crest: The fourth germ layer. J Oral Maxillofac Pathol 2015; 19:221-9. [PMID: 26604500 PMCID: PMC4611932 DOI: 10.4103/0973-029x.164536] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Accepted: 07/01/2015] [Indexed: 12/14/2022] Open
Abstract
The neural crest cells (NCCs), a transient group of cells that emerges from the dorsal aspect of the neural tube during early vertebrate development has been a fascinating group of cells because of its multipotency, long range migration through embryo and its capacity to generate a prodigious number of differentiated cell types. For these reasons, although derived from the ectoderm, the neural crest (NC) has been called the fourth germ layer. The non neural ectoderm, the neural plate and the underlying mesoderm are needed for the induction and formation of NC cells. Once formed, NC cells start migrating as a wave of cells, moving away from the neuroepithelium and quickly splitting into distinct streams. These migrating NCCs home in to different regions and give rise to plethora of tissues. Umpteen number of signaling molecules are essential for formation, epithelial mesenchymal transition, delamination, migration and localization of NCC. Authors believe that a clear understanding of steps and signals involved in NC formation, migration, etc., may help in understanding the pathogenesis behind cancer metastasis and many other diseases. Hence, we have taken this review to discuss the various aspects of the NC cells.
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Affiliation(s)
- K Shyamala
- Department of Oral and Maxillofacial Pathology, Rajarajeswari Dental College and Hospital No. 14, Ramohally Cross, Kumbalgodu, Mysore Road, Bengaluru - 560 060, Karnataka, India
| | - Sarita Yanduri
- Department of Oral and Maxillofacial Pathology, DAPMRV Dental College and Hospital, J P Nagar, Bengaluru, Karnataka, India
| | - HC Girish
- Department of Oral and Maxillofacial Pathology, Rajarajeswari Dental College and Hospital No. 14, Ramohally Cross, Kumbalgodu, Mysore Road, Bengaluru - 560 060, Karnataka, India
| | - Sanjay Murgod
- Department of Oral and Maxillofacial Pathology, Rajarajeswari Dental College and Hospital No. 14, Ramohally Cross, Kumbalgodu, Mysore Road, Bengaluru - 560 060, Karnataka, India
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Pippenger BE, Ventura M, Pelttari K, Feliciano S, Jaquiery C, Scherberich A, Walboomers XF, Barbero A, Martin I. Bone-forming capacity of adult human nasal chondrocytes. J Cell Mol Med 2015; 19:1390-9. [PMID: 25689393 PMCID: PMC4459852 DOI: 10.1111/jcmm.12526] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Accepted: 11/27/2014] [Indexed: 12/26/2022] Open
Abstract
Nasal chondrocytes (NC) derive from the same multipotent embryological segment that gives rise to the majority of the maxillofacial bone and have been reported to differentiate into osteoblast-like cells in vitro. In this study, we assessed the capacity of adult human NC, appropriately primed towards hypertrophic or osteoblastic differentiation, to form bone tissue in vivo. Hypertrophic induction of NC-based micromass pellets formed mineralized cartilaginous tissues rich in type X collagen, but upon implantation into subcutaneous pockets of nude mice remained avascular and reverted to stable hyaline-cartilage. In the same ectopic environment, NC embedded into ceramic scaffolds and primed with osteogenic medium only sporadically formed intramembranous bone tissue. A clonal study could not demonstrate that the low bone formation efficiency was related to a possibly small proportion of cells competent to become fully functional osteoblasts. We next tested whether the cues present in an orthotopic environment could induce a more efficient direct osteoblastic transformation of NC. Using a nude rat calvarial defect model, we demonstrated that (i) NC directly participated in frank bone formation and (ii) the efficiency of survival and bone formation by NC was significantly higher than that of reference osteogenic cells, namely bone marrow-derived mesenchymal stromal cells. This study provides a proof-of-principle that NC have the plasticity to convert into bone cells and thereby represent an easily available cell source to be further investigated for craniofacial bone regeneration.
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Affiliation(s)
- Benjamin E Pippenger
- Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Manuela Ventura
- Department of Biomaterials, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | - Karoliina Pelttari
- Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Sandra Feliciano
- Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Claude Jaquiery
- Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Arnaud Scherberich
- Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - X Frank Walboomers
- Department of Biomaterials, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | - Andrea Barbero
- Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Ivan Martin
- Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
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