|
1
|
Kanno H, Nakahara K, Yamada S, Fujii S, Murata H, Yamamoto T, Hasumi H, Yao M. Relationship between ZHX2 Expression and VHL Gene Alteration in VHL-associated and Sporadic Hemangioblastomas of the Central Nervous System. J Kidney Cancer VHL 2024; 11:39-47. [PMID: 39850947 PMCID: PMC11756601 DOI: 10.15586/jkcvhl.v11i4.355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 12/01/2024] [Indexed: 01/25/2025] Open
Abstract
Central nervous system hemangioblastoma (CNS-HB) is the most common manifestation of von Hippel-Lindau disease (VHL). The main axis of the CNS-HB pathway is the VHL-HIF signaling pathway. Recently, we proposed an alternative VHL-JAK-STAT pathway in CNS-HB. In contrast, the VHL substrate transcription factor zinc fingers and homeoboxes 2 (ZHX2) have been identified as the oncogenic drivers in VHL-deficient clear cell renal cell carcinoma (RCC). However, ZHX2 expression in CNS-HB has not been previously reported. Furthermore, the VHL-ZXH2-NF-κB signaling pathway in CNS-HB remains unresolved. In this study, we aimed to investigate ZHX2 expression and VHL gene alteration in CNS-HB and propose the role of ZHX2 in CNS-HB. Using the MACS method, Scl+ hemangioblastoma-like cells were isolated from multipotent nestin-expressing stem cells. The ubiquitination of ZHX2 in these cells and the immunoprecipitation between ZHX2 and VHL were investigated. In addition, the VHL genes of patients with hemangioblastoma were analyzed. ZHX2 expression in CNS-HB tissues was examined by immunohistochemistry and western blotting. In addition, VHL gene mutations in CNS-HB were analyzed by sequencing. The association between ZHX2 expression and VHL gene mutation was analyzed. ZHX2 was ubiquitinated in Scl+hemangioblastoma-like cells after the transfer of the VHL expression vector into these cells. ZHX2 expression in these cells was well detected before transfer but disappeared after the transfer. ZHX2 expression was detected in 18 of the 21 CNS-HB tissues by immunoblotting and/or immunohistochemistry. Sporadic CNS-HB showed weak expression, whereas VHL-related CNS-HB showed moderate or strong expression. In particular, CNS-HB with severe VHL gene mutations, including large deletions, showed strong or moderate ZHX2 expression. The association between VHL gene mutation and ZHX2 expression revealed a significant correlation between VHL gene alteration severity and the level of immunoblotting (P < 0.05). In conclusion, the severity of VHL gene alteration correlates with the level of ZHX2 expression. ZHX2 is predominantly expressed in CNS-HB, especially in VHL-related cases with severe VHL gene alterations, suggesting a potential role in tumorigenesis and proliferation of CNS-HB.
Collapse
Affiliation(s)
- Hiroshi Kanno
- Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
- Department of Neurosurgery, Asahi Hospital, Tokyo, Japan
- Department of Neurosurgery, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Kimihiro Nakahara
- Department of Neurosurgery, International University of Health and Welfare, Narita, Japan
| | - Sachiko Yamada
- Department of Neurosurgery, Asahi Hospital, Tokyo, Japan
| | - Satoshi Fujii
- Department of Neurosurgery, Asahi Hospital, Tokyo, Japan
| | - Hidetoshi Murata
- Department of Neurosurgery, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Tetsuya Yamamoto
- Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Hisashi Hasumi
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Masahiro Yao
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| |
Collapse
|
|
2
|
Kanno H, Matsumoto S, Yoshizumi T, Nakahara K, Kubo A, Murata H, Shuin T, U HS. Role of SOCS and VHL Proteins in Neuronal Differentiation and Development. Int J Mol Sci 2023; 24:ijms24043880. [PMID: 36835292 PMCID: PMC9960776 DOI: 10.3390/ijms24043880] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 02/08/2023] [Accepted: 02/09/2023] [Indexed: 02/17/2023] Open
Abstract
The basic helix-loop-helix factors play a central role in neuronal differentiation and nervous system development, which involve the Notch and signal transducer and activator of transcription (STAT)/small mother against decapentaplegic signaling pathways. Neural stem cells differentiate into three nervous system lineages, and the suppressor of cytokine signaling (SOCS) and von Hippel-Lindau (VHL) proteins are involved in this neuronal differentiation. The SOCS and VHL proteins both contain homologous structures comprising the BC-box motif. SOCSs recruit Elongin C, Elongin B, Cullin5(Cul5), and Rbx2, whereas VHL recruits Elongin C, Elongin B, Cul2, and Rbx1. SOCSs form SBC-Cul5/E3 complexes, and VHL forms a VBC-Cul2/E3 complex. These complexes degrade the target protein and suppress its downstream transduction pathway by acting as E3 ligases via the ubiquitin-proteasome system. The Janus kinase (JAK) is the main target protein of the E3 ligase SBC-Cul5, whereas hypoxia-inducible factor is the primary target protein of the E3 ligase VBC-Cul2; nonetheless, VBC-Cul2 also targets the JAK. SOCSs not only act on the ubiquitin-proteasome system but also act directly on JAKs to suppress the Janus kinase-signal transduction and activator of transcription (JAK-STAT) pathway. Both SOCS and VHL are expressed in the nervous system, predominantly in brain neurons in the embryonic stage. Both SOCS and VHL induce neuronal differentiation. SOCS is involved in differentiation into neurons, whereas VHL is involved in differentiation into neurons and oligodendrocytes; both proteins promote neurite outgrowth. It has also been suggested that the inactivation of these proteins may lead to the development of nervous system malignancies and that these proteins may function as tumor suppressors. The mechanism of action of SOCS and VHL involved in neuronal differentiation and nervous system development is thought to be mediated through the inhibition of downstream signaling pathways, JAK-STAT, and hypoxia-inducible factor-vascular endothelial growth factor pathways. In addition, because SOCS and VHL promote nerve regeneration, they are expected to be applied in neuronal regenerative medicine for traumatic brain injury and stroke.
Collapse
Affiliation(s)
- Hiroshi Kanno
- Department of Neurosurgery, School of Medicine, Yokohama City University, Yokohama 232-0024, Japan
- Department of Neurosurgery, Asahi Hospital, Tokyo 121-0078, Japan
- Correspondence: ; Tel.: +81-3-5242-5800
| | - Shutaro Matsumoto
- Department of Neurosurgery, School of Medicine, Yokohama City University, Yokohama 232-0024, Japan
- Department of Neurosurgery, Asahi Hospital, Tokyo 121-0078, Japan
| | - Tetsuya Yoshizumi
- Department of Neurosurgery, St. Mariannna Medical University, Kawasaki 216-8511, Japan
| | - Kimihiro Nakahara
- Department of Neurosurgery, International University of Health and Welfare, Atami 413-0012, Japan
| | | | - Hidetoshi Murata
- Department of Neurosurgery, St. Mariannna Medical University, Kawasaki 216-8511, Japan
| | - Taro Shuin
- Kochi Medical School Hospital, Nangoku 783-0043, Japan
| | - Hoi-Sang U
- Department of Electrical Engineering, University of California San Diego, San Diego, CA 92093, USA
| |
Collapse
|
|
3
|
Tenorio-Mina A, Cortés D, Esquivel-Estudillo J, López-Ornelas A, Cabrera-Wrooman A, Lara-Rodarte R, Escobedo-Avila I, Vargas-Romero F, Toledo-Hernández D, Estudillo E, Acevedo-Fernández JJ, Tapia JSO, Velasco I. Human Keratinocytes Adopt Neuronal Fates After In Utero Transplantation in the Developing Rat Brain. Cell Transplant 2021; 30:963689720978219. [PMID: 33435710 PMCID: PMC7809298 DOI: 10.1177/0963689720978219] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 11/02/2020] [Accepted: 11/12/2020] [Indexed: 11/30/2022] Open
Abstract
Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ectopic expression of transcription factors. In this article we tested the hypothesis that human keratinocytes can adopt neural fates after culturing them in suspension with a neural medium. Initially, keratinocytes expressed Keratins and Vimentin. After neural induction, transcriptional upregulation of NESTIN, SOX2, VIMENTIN, SOX1, and MUSASHI1 was observed, concomitant with significant increases in NESTIN detected by immunostaining. However, in vitro differentiation did not yield the expression of neuronal or astrocytic markers. We tested the differentiation potential of control and neural-induced keratinocytes by grafting them in the developing CNS of rats, through ultrasound-guided injection. For this purpose, keratinocytes were transduced with lentivirus that contained the coding sequence of green fluorescent protein. Cell sorting was employed to select cells with high fluorescence. Unexpectedly, 4 days after grafting these cells in the ventricles, both control and neural-induced cells expressed green fluorescent protein together with the neuronal proteins βIII-Tubulin and Microtubule-Associated Protein 2. These results support the notion that in vivo environment provides appropriate signals to evaluate the neuronal differentiation potential of keratinocytes or other non-neural cell populations.
Collapse
Affiliation(s)
- Andrea Tenorio-Mina
- Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico
| | - Daniel Cortés
- Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico
| | - Joel Esquivel-Estudillo
- Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico
- Unidad de Diagnóstico y Medicina Molecular, “Dr. Ruy Pérez Tamayo”, Hospital del Niño Morelense/Facultad de Medicina-UAEM, Zapata, Morelos, Mexico
| | - Adolfo López-Ornelas
- Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico
- División de Investigación, Hospital Juárez de México, Mexico City, Mexico
| | - Alejandro Cabrera-Wrooman
- Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
- Unidad de Diagnóstico y Medicina Molecular, “Dr. Ruy Pérez Tamayo”, Hospital del Niño Morelense/Facultad de Medicina-UAEM, Zapata, Morelos, Mexico
- Instituto Nacional de Rehabilitación, Mexico City, Mexico
| | - Rolando Lara-Rodarte
- Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico
| | - Itzel Escobedo-Avila
- Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
| | - Fernanda Vargas-Romero
- Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico
| | - Diana Toledo-Hernández
- Unidad de Diagnóstico y Medicina Molecular, “Dr. Ruy Pérez Tamayo”, Hospital del Niño Morelense/Facultad de Medicina-UAEM, Zapata, Morelos, Mexico
- Centro de Investigación en Dinámica Celular, Instituto de Ciencias, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico
| | - Enrique Estudillo
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico
| | | | - Jesús Santa-Olalla Tapia
- Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico
- Unidad de Diagnóstico y Medicina Molecular, “Dr. Ruy Pérez Tamayo”, Hospital del Niño Morelense/Facultad de Medicina-UAEM, Zapata, Morelos, Mexico
| | - Iván Velasco
- Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, Mexico
| |
Collapse
|
|
4
|
Kanno H, Yoshizumi T, Shinonaga M, Kubo A, Murata H, Yao M. Role of VHL-JAK-STAT signaling pathway in central nervous system hemangioblastoma associated with von Hippel-Lindau disease. J Neurooncol 2020; 148:29-38. [PMID: 32356150 DOI: 10.1007/s11060-020-03506-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 04/18/2020] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Central nervous system hemangioblastoma is a benign tumor associated with or without von Hippel-Lindau (VHL) disease which is an autosomal dominant hereditary disease that results from a germline mutation in the VHL gene. A main axis of signaling pathways in central nervous system hemangioblastoma is VHL-HIF signaling pathway. Here, we propose an alternative VHL-JAK-STAT signaling pathway in hemangioblastoma and discuss the role. METHODS Using MACS method, Scl+ hemangioblast-like cells were isolated from multipotent nestin-expressing stem cells. Then, ubiquitination of JAK2 in those cells and immunoprecipitation between JAK2 and VHL were examined. Then, expressions of JAK2 and STAT3 in those cells and expressions of VHL-associated hemangioblastoma tissues were examined. In addition, the VHL genes of patients bearing hemangioblastoma were analyzed. RESULTS JAK2 and STAT3 in Scl+ hemangioblast-like cells were ubiquitinated after VHL- expression vector was transferred to those cells. Expressions of JAK2 and STAT3 in those cells were well recognized before the transfer, but those disappeared after the transfer. Expressions of both JAK2 and STAT3 in hemangioblastoma tissues were well shown. The VHL gene analysis revealed that patients bearing hemangioblastoma carried missense mutations in 5, small deletions in 2, large deletions in 4, and nonsense mutation in 1 CONCLUSIONS: VHL-JAK-STAT signaling pathway might play an important role in proliferation, angiogenesis, and maintenance of stem-cell-nature in hemangioblastoma as an alternative signaling pathway to supplement VHL-HIF signaling pathway.
Collapse
Affiliation(s)
- Hiroshi Kanno
- Department of Neurosurgery, International University of Health and Welfare Atami Hospital, 13-1 Higashikaigan-cho, Atami, Shizuoka, 413-0012, Japan.
| | - Tetsuya Yoshizumi
- Department of Neurosurgery, International University of Health and Welfare Atami Hospital, 13-1 Higashikaigan-cho, Atami, Shizuoka, 413-0012, Japan
| | - Masamichi Shinonaga
- Department of Neurosurgery, International University of Health and Welfare Atami Hospital, 13-1 Higashikaigan-cho, Atami, Shizuoka, 413-0012, Japan
| | - Atsuhiko Kubo
- Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
| | - Hidetoshi Murata
- Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
| | - Masahiro Yao
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
| |
Collapse
|
|
5
|
Kosykh A, Beilin A, Sukhinich K, Vorotelyak E. Postnatal neural crest stem cells from hair follicle interact with nerve tissue in vitro and in vivo. Tissue Cell 2018; 54:94-104. [PMID: 30309515 DOI: 10.1016/j.tice.2018.08.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 08/16/2018] [Accepted: 08/17/2018] [Indexed: 01/05/2023]
Abstract
Neural crest stem cells that located in the postnatal hair follicle (HF-NCSC) are considered a promising tool for treatment of nervous system diseases and injuries. It is well known that HF-NCSC can be used in the spinal cord and sciatic nerve reparation but their ability to restore brain structures is poorly studied. In this article we are investigating the interaction between HF-NCSC and a nerve tissue (embryonic and adult). We have found out that HF-NCSC isolated from adult mice grow and differentiate in accordance with the mouse embryo developmental stage when co-cultured with the embryonic nerve tissue. The HF-NCSC migration is slower in the late embryonic tissue co-culture system compared to the early one. This phenomenon is related to the motor function of the cells but not to their proliferation level. We have demonstrated that the embryonic nerve tissue maintains HF-NCSC an undifferentiated status, while an adult brain tissue inhibits the cell proliferation and activates the differentiation processes. Besides, HF-NCSC pre-differentiated into the neuronal direction shows a higher survival and migration rate after the transplantation into the adult brain tissue compared to the undifferentiated HF-NCSC. Thus, we have investigated the postnatal HF-NCSC response to the nerve tissue microenvironment to analyze their possible application to the brain repair processes.
Collapse
Affiliation(s)
- Anastasiia Kosykh
- Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Vavilova 26, 119334, Moscow, Russian Federation; Pirogov Russian National Research Medical University, Ostrovitianova 1, 117997, Moscow, Russian Federation.
| | - Arkadii Beilin
- Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Vavilova 26, 119334, Moscow, Russian Federation
| | - Kirill Sukhinich
- Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Vavilova 26, 119334, Moscow, Russian Federation
| | - Ekaterina Vorotelyak
- Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Vavilova 26, 119334, Moscow, Russian Federation; Pirogov Russian National Research Medical University, Ostrovitianova 1, 117997, Moscow, Russian Federation; Lomonosov Moscow State University, Leninskie Gory 1, Moscow, Russian Federation
| |
Collapse
|
|
6
|
Patruno M, Melotti L, Gomiero C, Sacchetto R, Topel O, Martinello T. A mini-review of TAT-MyoD fused proteins: state of the art and problems to solve. Eur J Transl Myol 2017; 27:6039. [PMID: 29299217 PMCID: PMC5745379 DOI: 10.4081/ejtm.2017.6039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2016] [Revised: 10/17/2017] [Accepted: 10/17/2017] [Indexed: 11/28/2022] Open
Abstract
The transcriptional activator TAT is a small peptide essential for viral replication and possesses the property of entering the cells from the extracellular milieu, acting as a membrane shuttle. In order to safely differentiate cells an innovative methodology, based on the fusion of transcription factors and the TAT sequence, is discussed in this short review. In several studies, it has been demonstrated that TAT protein can be observed in the cell nucleus after few hours from the inoculation although its way of action is not fully understood. However, further studies will be necessary to develop this methodology for clinical purposes.
Collapse
Affiliation(s)
- Marco Patruno
- Department of Comparative Biomedicine and Food Science, University of Padova, Italy
| | - Luca Melotti
- Department of Comparative Biomedicine and Food Science, University of Padova, Italy
| | - Chiara Gomiero
- Department of Comparative Biomedicine and Food Science, University of Padova, Italy
| | - Roberta Sacchetto
- Department of Comparative Biomedicine and Food Science, University of Padova, Italy
| | - Ohad Topel
- VTH - Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Israel
| | - Tiziana Martinello
- Department of Comparative Biomedicine and Food Science, University of Padova, Italy
| |
Collapse
|
|
7
|
Wu W, Wu XL, Ji YQ, Gao Z. Differentiation of nestin‑negative human hair follicle outer root sheath cells into neurons in vitro. Mol Med Rep 2017; 16:95-100. [PMID: 28534946 PMCID: PMC5482136 DOI: 10.3892/mmr.2017.6585] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2016] [Accepted: 02/21/2017] [Indexed: 01/18/2023] Open
Abstract
A specialized quiescent population of hair follicle stem cells, residing in the hair follicle outer root sheath cells (ORSCs), has previously demonstrated pluripotency for differentiation into neural stem cells (NSCs). A previous study indicated that nestin-positive hair follicle ORSCs are able to differentiate into neurons. However, little has been reported on the isolation of nestin-negative human ORSCs and whether they can successfully differentiate into neurons in vitro. In the present study, nestin-positive ORSCs were significantly reduced with a prolonged incubation time in vitro. Following 9 days of primary culture, nestin-expressing ORSCs disappeared entirely, and ORSCs remained nestin-negative following 5 days of subculture. Notably, nestin was identified in ORSCs following a three-step process of neuro-induction. In addition, neruodevelopmental markers were detected in the ORSC-derived nestin-positive spherical cell mass, including the induction of the neuronal specific markers growth associated protein-43, neurotensin receptor-3 and p75 neurotrophin receptor, and also the gliocyte markers, glial fibrillary acidic protein and S100. These sphere-forming cells did not express the mature neuron-associated markers neurofilament medium, neuronal nuclei and neuron-specific enolase, which suggested that sphere-forming cells may preferentially differentiate into neural stem cell-like cells as opposed to mature neurons or neurogliocyte. In conclusion, ORSC-driven neural differentiation may be a suitable treatment strategy for neurodegenerative diseases and may possess an important value in regenerative medicine.
Collapse
Affiliation(s)
- Wei Wu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
| | - Xiao-Li Wu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
| | - Yu-Qing Ji
- Department of Plastic and Reconstructive Surgery, Shanghai General Hospital, Shanghai 200080, P.R. China
| | - Zhen Gao
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
| |
Collapse
|
|
8
|
Abstract
For decades, researchers have been fascinated by the strategy of using cell therapy for bone defects; some progress in the field has been made. Owing to its ample supply and easy access, skin, the largest organ in the body, has gained attention as a potential source of stem cells. Despite extensive applications in skin and nerve regeneration, an increasing number of reports indicate its potential use in bone tissue engineering and regeneration. Unfortunately, few review articles are available to outline current research efforts in skin-based osteogenesis. This review first summarizes the latest findings on stem cells or progenitors in skin and their niches and then discusses the strategies of skin cell-based osteogenesis. We hope this article elucidates this topic and generates new ideas for future studies.
Collapse
Affiliation(s)
- Tingliang Wang
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV, USA.,Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lian Zhu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ming Pei
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV, USA.,Division of Exercise Physiology, West Virginia University, Morgantown, WV, USA.,Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV, USA
| |
Collapse
|
|
9
|
Kuo YC, Chen CW. Neuroregeneration of Induced Pluripotent Stem Cells in Polyacrylamide-Chitosan Inverted Colloidal Crystal Scaffolds with Poly(lactide-co-glycolide) Nanoparticles and Transactivator of Transcription von Hippel-Lindau Peptide. Tissue Eng Part A 2017; 23:263-274. [PMID: 28107800 DOI: 10.1089/ten.tea.2016.0139] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Polyacrylamide (PAAM) and chitosan were fabricated by inverted colloidal crystal (ICC) method for scaffolds comprising regular pores. The hybrid PAAM-chitosan ICC scaffolds were grafted with poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) for a rougher pore surface and grafted with transactivator of transcription von Hippel-Lindau (TATVHL) peptide for a better differentiation of induced pluripotent stem (iPS) cells toward neural lineage. By scanning electron microscopy, we found that iPS cells cultured in PAAM-chitosan ICC scaffolds with PLGA NPs at 1.0 mg/mL and TATVHL peptide at 15 μg/mL elongated the axonal length to 15 μm. A combination of PLGA NPs and TATVHL peptide favored the adhesion of iPS cells, reduced the embryonic phenotype after cultivation, and guided the production of βIII tubulin-positive cells in PAAM-chitosan ICC scaffolds. In addition to the differentiation toward neurite-like cells, an increase in the content of TATVHL peptide in PAAM-chitosan ICC scaffolds inhibited the differentiation of iPS cells toward astrocytes. ICC scaffolds composed of PAAM, chitosan, PLGA NPs, and TATVHL peptide can be an efficacious matrix to differentiate iPS cells toward neurons and retard the glial formation for nerve regeneration.
Collapse
Affiliation(s)
- Yung-Chih Kuo
- Department of Chemical Engineering, National Chung Cheng University , Chia-Yi, Taiwan, Republic of China
| | - Chun-Wei Chen
- Department of Chemical Engineering, National Chung Cheng University , Chia-Yi, Taiwan, Republic of China
| |
Collapse
|
|
10
|
IgG and IgA with potential microbial-binding activity are expressed by normal human skin epidermal cells. Int J Mol Sci 2015; 16:2574-90. [PMID: 25625513 PMCID: PMC4346852 DOI: 10.3390/ijms16022574] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Revised: 11/25/2014] [Accepted: 01/07/2015] [Indexed: 12/18/2022] Open
Abstract
The innate immune system of the skin is thought to depend largely on a multi-layered mechanical barrier supplemented by epidermis-derived antimicrobial peptides. To date, there are no reports of antimicrobial antibody secretion by the epidermis. In this study, we report the expression of functional immunoglobulin G (IgG) and immunoglobulin A (IgA), previously thought to be only produced by B cells, in normal human epidermal cells and the human keratinocyte line HaCaT. While B cells express a fully diverse Ig, epidermal cell-expressed IgG or IgA showed one or two conservative VHDJH rearrangements in each individual. These unique VDJ rearrangements in epidermal cells were found neither in the B cell-derived Ig VDJ databases published by others nor in our positive controls. IgG and IgA from epidermal cells of the same individual had different VDJ rearrangement patterns. IgG was found primarily in prickle cells, and IgA was mainly detected in basal cells. Both epidermal cell-derived IgG and IgA showed potential antibody activity by binding pathogens like Staphylococcus aureus, the most common pathogenic skin bacteria, but the microbial-binding profile was different. Our data indicates that normal human epidermal cells spontaneously express IgG and IgA, and we speculate that these Igs participate in skin innate immunity.
Collapse
|
|
11
|
Alibardi L. Immunolocalization of Nestin in the lizard Podarcis muralis indicates up-regulation during the process of tail regeneration and epidermal differentiation. Ann Anat 2014; 196:135-43. [DOI: 10.1016/j.aanat.2013.12.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2013] [Revised: 12/03/2013] [Accepted: 12/06/2013] [Indexed: 01/03/2023]
|
|
12
|
Kanno H. Regenerative therapy for neuronal diseases with transplantation of somatic stem cells. World J Stem Cells 2013; 5:163-171. [PMID: 24179604 PMCID: PMC3812520 DOI: 10.4252/wjsc.v5.i4.163] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Revised: 07/21/2013] [Accepted: 10/16/2013] [Indexed: 02/06/2023] Open
Abstract
Pluripotent stem cells, which are capable of differentiating in various species of cells, are hoped to be donor cells in transplantation in regenerative medicine. Embryonic stem (ES) cells and induced pluripotent stem cells have the potential to differentiate in approximately all species of cells. However, the proliferating ability of these cells is high and the cancer formation ability is also recognized. In addition, ethical problems exist in using ES cells. Somatic stem cells with the ability to differentiate in various species of cells have been used as donor cells for neuronal diseases, such as amyotrophic lateral sclerosis, spinal cord injury, Alzheimer disease, cerebral infarction and congenital neuronal diseases. Human mesenchymal stem cells derived from bone marrow, adipose tissue, dermal tissue, umbilical cord blood and placenta are usually used for intractable neuronal diseases as somatic stem cells, while neural progenitor/stem cells and retinal progenitor/stem cells are used for a few congenital neuronal diseases and retinal degenerative disease, respectively. However, non-treated somatic stem cells seldom differentiate to neural cells in recipient neural tissue. Therefore, the contribution to neuronal regeneration using non-treated somatic stem cells has been poor and various differential trials, such as the addition of neurotrophic factors, gene transfer, peptide transfer for neuronal differentiation of somatic stem cells, have been performed. Here, the recent progress of regenerative therapies using various somatic stem cells is described.
Collapse
|