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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.
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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
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Kanno H, Matsumoto S, Yoshizumi T, Nakahara K, Shinonaga M, Kubo A, Fujii S, Ishizuka Y, Tanaka M, Ichihashi M, Murata H. SOCS7-Derived BC-Box Motif Peptide Mediated Cholinergic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells. Int J Mol Sci 2023; 24:ijms24032786. [PMID: 36769102 PMCID: PMC9917589 DOI: 10.3390/ijms24032786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 01/20/2023] [Accepted: 01/21/2023] [Indexed: 02/04/2023] Open
Abstract
Adipose-derived mesenchymal stem cells (ADMSCs) are a type of pluripotent somatic stem cells that differentiate into various cell types such as osteoblast, chondrocyte, and neuronal cells. ADMSCs as donor cells are used to produce regenerative medicines at hospitals and clinics. However, it has not been reported that ADMSCs were differentiated to a specific type of neuron with a peptide. Here, we report that ADMSCs differentiate to the cholinergic phenotype of neurons by the SOCS7-derived BC-box motif peptide. At operations for patients with neurological disorders, a small amount of subcutaneous fat was obtained. Two weeks later, adipose-derived mesenchymal stem cells (ADMSCs) were isolated and cultured for a further 1 to 2 weeks. Flow cytometry analysis for characterization of ADMSCs was performed with CD73, CD90, and CD105 as positive markers, and CD14, CD31, and CD56 as negative markers. The results showed that cultured cells were compatible with ADMSCs. Immunocytochemical studies showed naïve ADMSCs immunopositive for p75NTR, RET, nestin, keratin, neurofilament-M, and smooth muscle actin. ADMSCs were suggested to be pluripotent stem cells. A peptide corresponding to the amino-acid sequence of BC-box motif derived from SOCS7 protein was added to the medium at a concentration of 2 μM. Three days later, immunocytochemistry analysis, Western blot analysis, ubiquitination assay, and electrophysiological analysis with patch cramp were performed. Immunostaining revealed the expression of neurofilament H (NFH), choline acetyltransferase (ChAT), and tyrosine hydroxylase (TH). In addition, Western blot analysis showed an increase in the expression of NFH, ChAT, and TH, and the expression of ChAT was more distinct than TH. Immunoprecipitation with JAK2 showed an increase in the expression of ubiquitin. Electrophysiological analysis showed a large holding potential at the recorded cells through path electrodes. The BC-box motif peptide derived from SOCS7 promoted the cholinergic differentiation of ADMSCs. This novel method will contribute to research as well as regenerative medicine for cholinergic neuron diseases.
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Affiliation(s)
- Hiroshi Kanno
- Department of Neurosurgery, Yokohama City University, Yokohama 236-0004, Japan
- Department of Neurosurgery, Asahi Hospital, Tokyo 121-0078, Japan
- Department of Neurosurgery, International University of Health and Welfare Atami Hospital, Atami 413-0012, Japan
- Correspondence: ; Tel.: +81-3-5243-5800; Fax: +81-3-5242-5826
| | - Shutaro Matsumoto
- Department of Neurosurgery, Yokohama City University, Yokohama 236-0004, Japan
- Department of Neurosurgery, Asahi Hospital, Tokyo 121-0078, Japan
| | - Tetsuya Yoshizumi
- Department of Neurosurgery, Yokohama City University, Yokohama 236-0004, Japan
- Department of Neurosurgery, International University of Health and Welfare Atami Hospital, Atami 413-0012, Japan
- Department of Neurosurgery, St. Marianna Medical University of Medicine, Kawasaki 216-8511, Japan
| | - Kimihiro Nakahara
- Department of Neurosurgery, International University of Health and Welfare Atami Hospital, Atami 413-0012, Japan
| | - Masamichi Shinonaga
- Department of Neurosurgery, International University of Health and Welfare Atami Hospital, Atami 413-0012, Japan
| | | | - Satoshi Fujii
- Department of Neurosurgery, Asahi Hospital, Tokyo 121-0078, Japan
| | | | | | | | - Hidetoshi Murata
- Department of Neurosurgery, St. Marianna Medical University of Medicine, Kawasaki 216-8511, Japan
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pH-dependent reversibly activatable cell-penetrating peptides improve the antitumor effect of artemisinin-loaded liposomes. J Colloid Interface Sci 2020; 586:391-403. [PMID: 33189320 DOI: 10.1016/j.jcis.2020.10.103] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 10/23/2020] [Accepted: 10/24/2020] [Indexed: 12/16/2022]
Abstract
Artemisinin (ART) is well known as an antimalarial drug, and it can also be used to treat inflammation as well as cancer. Although many researchers have reported the antitumor activity of ART, most of these studies were investigated in vitro. In addition, ART is sparingly soluble in water, limiting its clinical relevance in drug development. Based on the data from our preliminary study, ART is not cytotoxic at low micromolar concentrations. Thus, we hypothesized that smart nanocarriers are beneficial for not only increasing the solubility of ART but also elevating the concentration of the drug at the target, thereby inducing the ideal antitumor effect. In this article, a reversibly activatable cell-penetrating peptide ((HE)10-G5-R6 or HE-R6) was introduced to modify artemisinin (ART)-loaded liposomes (ART-Lip-HE-R6) against tumors, and in vitro and in vivo performance were investigated. ART-Lip-HE-R6 exhibited sustained release under different pH conditions. The internalization and cytotoxicity of liposomes were enhanced at low pH, i.e., 6.5, after modification with HE-R6 versus nonmodified liposomes. Moreover, a longer retention time in tumors could be observed in the ART-Lip-HE-R6 group, followed by higher efficiency of tumor suppression. In conclusion, Lip-HE-R6 might be a promising delivery system for ART in cancer therapy.
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Yoshizumi T, Kubo A, Murata H, Shinonaga M, Kanno H. BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons. Int J Mol Sci 2020; 21:ijms21144947. [PMID: 32668737 PMCID: PMC7403999 DOI: 10.3390/ijms21144947] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 07/09/2020] [Accepted: 07/11/2020] [Indexed: 12/11/2022] Open
Abstract
The BC-box motif in suppressor of cytokine signaling 6 (SOCS6) promotes the neuronal differentiation of somatic stem cells, including epidermal stem cells. SOCS6 protein belongs to the group of SOCS proteins and inhibits cytokine signaling. Here we showed that epidermal stem cells were induced to differentiate into GABAnergic neurons by the intracellular delivery of a peptide composed of the amino-acid sequences encoded by the BC-box motif in SOCS6 protein. The BC-box motif (SLQYLCRFVI) in SOCS6 corresponded to the binding site of elongin BC. GABAnergic differentiation mediated by the BC-box motif in SOCS6 protein was caused by ubiquitination of JAK2 and inhibition of the JAK2-STAT3 pathway. Furthermore, GABAnergic neuron-like cells generated from epidermal stem cells were transplanted into the brain of a rodent ischemic model. Then, we demonstrated that these transplanted cells were GAD positive and that the cognitive function of the ischemic model rodents with the transplanted cells was improved. This study could contribute to not only elucidating the mechanism of GABAnergic neuronal differentiation but also to neuronal regenerative medicine utilizing GABAnergic neurons.
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Affiliation(s)
- Tetsuya Yoshizumi
- Department of Neurosurgery, International University of Health and Welfare Atami Hospital, Atami 413-0012, Japan; (T.Y.); (M.S.)
| | - Atsuhiko Kubo
- Nerve Care Clinic, Yokosuka 238-0012, Japan;
- Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan;
| | - Hidetoshi Murata
- Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan;
| | - Masamichi Shinonaga
- Department of Neurosurgery, International University of Health and Welfare Atami Hospital, Atami 413-0012, Japan; (T.Y.); (M.S.)
| | - Hiroshi Kanno
- Department of Neurosurgery, International University of Health and Welfare Atami Hospital, Atami 413-0012, Japan; (T.Y.); (M.S.)
- Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan;
- Correspondence: ; Tel.: +81-557-81-9171; Fax: +81-557-83-6632
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Kozaki I, Shimizu K, Honda H. Disulfide linked hetero dimeric peptide arrays for screening functional peptides inside cells. J Biosci Bioeng 2020; 129:613-618. [DOI: 10.1016/j.jbiosc.2019.11.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 11/14/2019] [Accepted: 11/25/2019] [Indexed: 01/06/2023]
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Bergeron L, Busuttil V, Botto JM. Multipotentiality of skin-derived precursors: application to the regeneration of skin and other tissues. Int J Cosmet Sci 2020; 42:5-15. [PMID: 31612512 DOI: 10.1111/ics.12587] [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: 08/01/2019] [Accepted: 10/12/2019] [Indexed: 12/13/2022]
Abstract
Skin-derived precursors (SKPs) have been described as multipotent dermal precursors. Here, we provide a review of the breadth and depth of scientific literature and studies regarding SKPs, accounting for a large number of scientific publications. Interestingly, these progenitors can be isolated from embryonic and adult skin, as well as from a population of dermal cells cultured in vitro in monolayer. Gathering information from different authors, this review explores different aspects of the SKP theme, such as the potential distinct origins of SKPs in rodents and in humans, and also their ability to differentiate in vitro and in vivo into multiple lineages of different progeny. This remarkable capacity makes SKPs an interesting endogenous source of precursors to explore in the framework of experimental and therapeutic applications in different domains. SKPs are not only involved in the skin's dermal maintenance and support as well as wound healing, but also in hair follicle morphogenesis. This review points out the interests of future researches on SKPs for innovative perspectives that may be helpful in many different types of scientific and medical domains.
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Affiliation(s)
- L Bergeron
- Ashland Specialties France, Global Skin Research Center, 655, route du Pin Montard, 06904, Sophia Antipolis, France
| | - V Busuttil
- Ashland Specialties France, Global Skin Research Center, 655, route du Pin Montard, 06904, Sophia Antipolis, France
| | - J-M Botto
- Ashland Specialties France, Global Skin Research Center, 655, route du Pin Montard, 06904, Sophia Antipolis, France
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BC-Box Motif-Mediated Neuronal Differentiation of Somatic Stem Cells. Int J Mol Sci 2018; 19:ijms19020466. [PMID: 29401731 PMCID: PMC5855688 DOI: 10.3390/ijms19020466] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 01/29/2018] [Accepted: 02/02/2018] [Indexed: 11/17/2022] Open
Abstract
Von Hippel-Lindau tumor suppressor protein (pVHL) functions to induce neuronal differentiation of neural stem/progenitor cells (NSCs) and skin-derived precursors (SKPs). Here we identified a neuronal differentiation domain (NDD) in pVHL. Neuronal differentiation of SKPs was induced by intracellular delivery of a peptide composed of the amino-acid sequences encoded by the NDD. Neuronal differentiation mediated by the NDD was caused by the binding between it and elongin C followed by Janus kinase-2 (JAK2) ubiquitination of JAK2 and inhibition of the JAK2/the signal transducer and activator of transcription-3(STAT)3 pathway. The NDD in pVHL contained the BC-box motif ((A,P,S,T)LXXX (A,C) XXX(A,I,L,V)) corresponding to the binding site of elongin C. Therefore, we proposed that other BC-box proteins might also contain an NDD; and subsequently also identified in them an NDD containing the amino-acid sequence encoded by the BC-box motif in BC-box proteins. Furthermore, we showed that different NDD peptide-delivered cells differentiated into different kinds of neuron-like cells. That is, dopaminergic neuron-like cells, cholinergic neuron-like cells, GABAnergic neuron-like cells or rhodopsin-positive neuron-like cells were induced by different NDD peptides. These novel findings might contribute to the development of a new method for promoting neuronal differentiation and shed further light on the mechanism of neuronal differentiation of somatic stem cells.
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Kozaki I, Shimizu K, Honda H. Effective modification of cell death-inducing intracellular peptides by means of a photo-cleavable peptide array-based screening system. J Biosci Bioeng 2017; 124:209-214. [DOI: 10.1016/j.jbiosc.2017.03.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Accepted: 03/22/2017] [Indexed: 10/19/2022]
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陈 若, 苗 勇, 胡 志. [Research progress of skin-derived precursor cells]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2017; 37:420-422. [PMID: 28377365 PMCID: PMC6780441 DOI: 10.3969/j.issn.1673-4254.2017.03.26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Indexed: 06/07/2023]
Abstract
As a novel population of neural crest-origin precursor cells, skin-derived precursor cells (SKPs) can be isolated from both embryonic and adult dermis. These cells have important values for research and potential clinical application in wound healing, organ regeneration and disease treatment for advantages in the abundance of cell sources, accessibility, potential of multipotent differentiation, and absence of ethical concerns. Here we review the developmental and anatomical origins of SKPs and their potential application in regenerative medicine. SKPs originate from the embryonic neural crest, and their sources may vary in different areas of the body. SKPs are widely found in the dermis, especially in the dermal papilla (DP), which was known as a niche of SKPs. The multipotent SKPs can used for autologous transplantation and are of vital importance in tissue repair.
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Affiliation(s)
- 若思 陈
- 南方医科大学南方医院，广东 广州 510515Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
- 约翰·霍普金斯大学医学院，马里兰州 巴尔的摩市Medical College，The Johns Hopkins University, Baltimore, United States of America
| | - 勇 苗
- 南方医科大学南方医院，广东 广州 510515Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 志奇 胡
- 南方医科大学南方医院，广东 广州 510515Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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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.
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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
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Effects of the properties of short peptides conjugated with cell-penetrating peptides on their internalization into cells. Sci Rep 2015; 5:12884. [PMID: 26256261 PMCID: PMC4530456 DOI: 10.1038/srep12884] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 07/13/2015] [Indexed: 12/14/2022] Open
Abstract
Peptides, especially intracellular functional peptides that can play a particular role inside a cell, have attracted attention as promising materials to control cell fate. However, hydrophilic materials like peptides are difficult for cells to internalize. Therefore, the screening and design of intracellular functional peptides are more difficult than that of extracellular ones. An effective high-throughput screening system for intracellular functional peptides has not been reported. Here, we demonstrate a novel peptide array system for screening intracellular functional peptides, in which both cell-penetrating peptide (CPP) domain and photo-cleavable linkers are used. By using this screening system, we determined how the cellular uptake properties of CPP-conjugated peptides varied depending on the properties of the conjugated peptides. We found that the internalization ability of CPP-conjugated peptides varied greatly depending on the property of the conjugated peptides, and anionic peptides drastically decreased the uptake ability. We summarized our data in a scatter diagram that plots hydrophobicity versus isoelectric point (pI) of conjugated peptides. These results define a peptide library suitable for screening of intracellular functional peptides. Thus, our system, including the diagram, is a promising tool for searching biological active molecules such as peptide-based drugs.
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Weber M, Apostolova G, Widera D, Mittelbronn M, Dechant G, Kaltschmidt B, Rohrer H. Alternative Generation of CNS Neural Stem Cells and PNS Derivatives from Neural Crest-Derived Peripheral Stem Cells. Stem Cells 2015; 33:574-88. [DOI: 10.1002/stem.1880] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 08/28/2014] [Accepted: 09/06/2014] [Indexed: 11/11/2022]
Affiliation(s)
- Marlen Weber
- Max-Planck-Institute for Brain Research, Research Group Developmental Neurobiology; Frankfurt Germany
| | - Galina Apostolova
- Innsbruck Medical University, Institute for Neuroscience; Innsbruck Austria
| | - Darius Widera
- Institute of Cell Biology, University of Bielefeld; Bielefeld Germany
| | | | - Georg Dechant
- Innsbruck Medical University, Institute for Neuroscience; Innsbruck Austria
| | - Barbara Kaltschmidt
- Institute of Cell Biology, University of Bielefeld; Bielefeld Germany
- Molecular Neurobiology; University of Bielefeld; Bielefeld Germany
| | - Hermann Rohrer
- Max-Planck-Institute for Brain Research, Research Group Developmental Neurobiology; Frankfurt Germany
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Müller J, Ossig C, Greiner JFW, Hauser S, Fauser M, Widera D, Kaltschmidt C, Storch A, Kaltschmidt B. Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats. Stem Cells Transl Med 2014; 4:31-43. [PMID: 25479965 DOI: 10.5966/sctm.2014-0078] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model.
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Affiliation(s)
- Janine Müller
- Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany
| | - Christiana Ossig
- Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany
| | - Johannes F W Greiner
- Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany
| | - Stefan Hauser
- Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany
| | - Mareike Fauser
- Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany
| | - Darius Widera
- Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany
| | - Christian Kaltschmidt
- Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany
| | - Alexander Storch
- Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany
| | - Barbara Kaltschmidt
- Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany
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Dai X, Lu X, Cheng F, Hao H, Qian T, Yu W, Tang L, Li L. Neurogenin 2 enhances the neuronal differentiation of skin-derived precursors. Int J Neurosci 2014; 125:367-74. [DOI: 10.3109/00207454.2014.935375] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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15
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Chen Z, Wang Y, Shi C. Therapeutic Implications of Newly Identified Stem Cell Populations From the Skin Dermis. Cell Transplant 2014; 24:1405-22. [PMID: 24972091 DOI: 10.3727/096368914x682431] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Skin, the largest organ of the body, is a promising reservoir for adult stem cells. The epidermal stem cells and hair follicle stem cells have been well studied for their important roles in homeostasis, regeneration, and repair of the epidermis and appendages for decades. However, stem cells residing in dermis were not identified until the year 2001, when a variety of stem cell subpopulations have been isolated and identified from the dermis of mammalian skin such as neural crest stem cells, mesenchymal stem cell-like dermal stem cells, and dermal hematopoietic cells. These stem cell subpopulations exhibited capabilities of self-renewing, multipotent differentiating, and immunosuppressive properties. Hence, the dermis-derived stem cells showed extensive potential applications in regenerative medicine, especially for wound healing/tissue repair, neural repair, and hematopoietic recovery. Here we summarized current research on the stem cell subpopulations derived from the dermis and aimed to provide a comprehensive review on their isolation, specific markers, differentiation capacity, and the functional activities in homeostasis, regeneration, and tissue repair.
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Affiliation(s)
- Zelin Chen
- Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China
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16
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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.
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Isolation of multipotent nestin-expressing stem cells derived from the epidermis of elderly humans and TAT-VHL peptide-mediated neuronal differentiation of these cells. Int J Mol Sci 2013; 14:9604-17. [PMID: 23644888 PMCID: PMC3676801 DOI: 10.3390/ijms14059604] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2013] [Revised: 04/17/2013] [Accepted: 04/23/2013] [Indexed: 02/07/2023] Open
Abstract
A specialized population of cells residing in the hair follicle is quiescent but shows pluripotency for differentiating into epithelial-mesenchymal lineage cells. Therefore, such cells are hoped to be useful as implantable donor cells for regenerative therapy. Recently, it was reported that intracellular delivery of TAT-VHL peptide induces neuronal differentiation of skin-derived precursors. In the present study, we successfully isolated multipotent stem cells derived from the epidermis of elderly humans, characterized these cells as being capable of sphere formation and strong expression of nestin, fibronectin, and CD34 but not of keratin 15, and identified the niche of these cells as being the outer root sheath of the hair follicles. In addition, we showed that TAT-VHL peptide induced their neuronal differentiation in vitro, and confirmed by fluorescence immunohistochemistry the neuronal differentiation of such peptide-treated cells implanted into rodent brains. These multipotent nestin-expressing stem cells derived from human epidermis are easily accessible and should be useful as donor cells for neuronal regenerative cell therapy.
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18
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TATVHL peptide-grafted alginate/poly(γ-glutamic acid) scaffolds with inverted colloidal crystal topology for neuronal differentiation of iPS cells. Biomaterials 2012; 33:8955-66. [PMID: 22998813 DOI: 10.1016/j.biomaterials.2012.08.073] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Accepted: 08/31/2012] [Indexed: 11/20/2022]
Abstract
The neuronal differentiation of induced pluripotent stem (iPS) cells in scaffolding biomaterials is an emerging issue in nervous regeneration and repair. This study presents the production of neuron-lineage cells from iPS cells in inverted colloidal crystal (ICC) scaffolds comprising alginate, poly(γ-glutamic acid) (γ-PGA), and TATVHL peptide. The ability of iPS cells to differentiate toward neurons in the constructs was demonstrated by flow-cytometeric sorting and immunochemical staining. The results revealed that hexagonally arrayed microspheres molded alginate/γ-PGA hydrogel into ICC topology with adequate interconnected pores. An increase in the quantity of surface TATVHL peptide enhanced the atomic ratio of nitrogen and the adhesion efficiency of iPS cells in constructs. However, the effect of TATVHL peptide on the viability of iPS cells was insignificant. The adhesion and viability of iPS cells in ICC constructs was higher than those in freeform ones. TATVHL peptide raised the percentage of β III tubulin-identified cells differentiating from iPS cells, indicating that TATVHL peptide stimulated the neuronal development in alginate/γ-PGA ICC constructs. TATVHL peptide-grafted alginate/γ-PGA ICC scaffolds can be promising for establishing nerve tissue from iPS cells.
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García-Parra P, Cavaliere F, Maroto M, Bilbao L, Obieta I, López de Munain A, Alava JI, Izeta A. Modeling neural differentiation on micropatterned substrates coated with neural matrix components. Front Cell Neurosci 2012; 6:10. [PMID: 22435050 PMCID: PMC3303083 DOI: 10.3389/fncel.2012.00010] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2011] [Accepted: 02/28/2012] [Indexed: 01/28/2023] Open
Abstract
Topographical and biochemical characteristics of the substrate are critical for neuronal differentiation including axonal outgrowth and regeneration of neural circuits in vivo. Contact stimuli and signaling molecules allow neurons to develop and stabilize synaptic contacts. Here we present the development, characterization and functional validation of a new polymeric support able to induce neuronal differentiation in both PC12 cell line and adult primary skin-derived precursor cells (SKPs) in vitro. By combining a photolithographic technique with use of neural extracellular matrix (ECM) as a substrate, a biocompatible and efficient microenvironment for neuronal differentiation was developed.
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Affiliation(s)
- Patricia García-Parra
- Biomaterials-Tissue Engineering Unit, Tecnalia Research and Innovation San Sebastian, Spain
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20
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Lebonvallet N, Boulais N, Le Gall C, Chéret J, Pereira U, Mignen O, Bardey V, Jeanmaire C, Danoux L, Pauly G, Misery L. Characterization of neurons from adult human skin-derived precursors in serum-free medium : a PCR array and immunocytological analysis. Exp Dermatol 2012; 21:195-200. [DOI: 10.1111/j.1600-0625.2011.01422.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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21
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Kuo YC, Wang CC. Cartilage regeneration by culturing chondrocytes in scaffolds grafted with TATVHL peptide. Colloids Surf B Biointerfaces 2012; 93:235-40. [PMID: 22305121 DOI: 10.1016/j.colsurfb.2012.01.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2011] [Revised: 01/10/2012] [Accepted: 01/11/2012] [Indexed: 10/14/2022]
Abstract
Formation of neocartilage is a critical issue in contemporary regenerative medicine. This study presents the generation of tissue engineering cartilage in TATVHL peptide-grafted scaffolds. Bovine knee chondrocytes were seeded in TATVHL peptide-grafted scaffolds and cultured in a spinner bioreactor. The results revealed that surface TATVHL peptide enhanced the adhesion of bovine knee chondrocytes in scaffolds. However, an increase in the concentration of TATVHL peptide in scaffolds (up to 20 μg/mL) did not cause an evident variation in the cell viability. Surface TATVHL peptide was effective in promoting the quantity of cartilaginous components in constructs after dynamic cultivation. Biochemical assay, scanning electron microscope images, and histological staining demonstrated that surface TATVHL peptide accelerated the proliferation of bovine knee chondrocytes in constructs. In addition, the secretion of glycosaminoglycans and production of collagen in TATVHL peptide-grafted constructs were faster than those in TATVHL peptide-free constructs. TATVHL peptide can be a promising bioactive molecule to improve chondrogenesis in porous biomaterials.
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Affiliation(s)
- Yung-Chih Kuo
- Department of Chemical Engineering National Chung Cheng University Chia-Yi, Taiwan, Republic of China.
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22
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Pawitan JA. Prospect of cell therapy for Parkinson's disease. Anat Cell Biol 2011; 44:256-64. [PMID: 22254154 PMCID: PMC3254879 DOI: 10.5115/acb.2011.44.4.256] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2011] [Revised: 09/05/2011] [Accepted: 09/27/2011] [Indexed: 01/01/2023] Open
Abstract
The hallmark of Parkinson's disease is on-going degeneration of dopaminergic neurons in the substantia nigra, which may be due to various etiologies. Various approaches to alleviate symptoms are available, such as life-long pharmacological intervention, deep brain stimulation, and transplantation of dopaminergic neuron-containing fetal tissue. However, each of these approaches has a disadvantage. Several studies have shown that various kinds of stem cells, induced pluripotent stem cells, and other cells can differentiate into dopaminergic neurons and may be promising for treating Parkinson's disease in the future. Therefore, this review addresses those cells in terms of their prospects in cell therapy for Parkinson's disease. In addition, the need for safety and efficacy studies, various cell delivery modes and sites, and possible side effects will be discussed.
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Higashida T, Jitsuki S, Kubo A, Mitsushima D, Kamiya Y, Kanno H. Skin-derived precursors differentiating into dopaminergic neuronal cells in the brains of Parkinson disease model rats. J Neurosurg 2010; 113:648-55. [PMID: 20302395 DOI: 10.3171/2010.2.jns091432] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECT In the authors' previous study, they observed that amino acids 157-171 of von Hippel-Lindau protein (VHL peptide) induced neuronal differentiation of skin-derived precursors. They also noted that transplantation of these differentiated cells into the striata of a Parkinson disease (PD) rat model reduced apomorphine-induced rotations. In the present study, they investigated if these cells produce dopamine in the striatum. METHODS Skin-derived precursors were differentiated into neurons using VHL peptide and transplanted into the striata of a PD model of rats. Four weeks after transplantation, a probe was inserted into rat striata and extracellular dopamine was extracted by microdialysis. Dopamine levels were measured by high-pressure liquid chromatography. Brain sections were assessed by immunohistochemical analysis for the presence of tyrosine hydroxylase and dopamine transporter. RESULTS Increased dopamine levels in the striata of the rats were observed after transplantation (p < 0.01), and these were correlated with a reduction in the number of apomorphine-induced rotations (p < 0.05). Skin-derived precursors observed along the tract of transplantation were positive for tyrosine hydroxylase and dopamine transporter. CONCLUSIONS This study suggests that transplantation of skin-derived precursors, differentiated into neuronal cells using VHL peptide, can improve PD-like symptoms by enabling production of dopamine in the striata in a PD model of rats.
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Affiliation(s)
- Tetsuhiro Higashida
- Department of Neurosurgery, Yokohama City University, School of Medicine, Yokohama, Kanagawa, Japan.
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Qiu Z, Miao C, Li J, Lei X, Liu S, Guo W, Cao Y, Duan EK. Skeletal myogenic potential of mouse skin-derived precursors. Stem Cells Dev 2010; 19:259-68. [PMID: 19594362 DOI: 10.1089/scd.2009.0058] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Cell transplantation-based therapy could be an effective way for the treatment of many diseases. Among numerous somatic stem cells isolated and purified, skin-derived precursors (SKPs) are abundant autologous cells, providing a large reservoir of cells for therapeutic transplantation. Previous studies showed that SKPs could be differentiated into neural and mesodermal progeny in vitro. In the present study, we attempted to differentiate SKPs to muscle progenitors in vitro. After treatment with a combination of growth factors, SKPs were differentiated into cells expressing markers of muscle progenitors, including Pax7. Furthermore, some of these cells expressed desmin, TnT, Mstn, and Myog, suggesting their differentiation into the muscular lineage. After single point injection, the differentiation of SKPs from green fluorescent protein positive donors into muscle precursors was also demonstrated in vivo. Additionally, donor SKPs migrated to the niche of muscle progenitors, participated in the regeneration of recipient muscles, and expressed markers of muscle progenitors, including Pax7, M-cadherin, and MyoD. After recovery of donor cells from recipient muscles at 3 weeks postinjection, some of the injected SKPs were converted to myogenic precursors, based on the expression of specific markers (Pax7 and MyoD). Some of these donor cells also expressed muscle makers (desmin, TnT, and Myog). At 20 weeks postinjection, the injected SKPs were localized to recipient muscles without decreases in their population size. In summary, these findings indicated that SKPs could develop into muscle progenitors and differentiated muscle cells in vitro and in vivo, thus providing valuable autologous cells for the treatment of muscle diseases.
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Affiliation(s)
- Zhifang Qiu
- State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, Beijing, People's Republic of China. , Graduate University of the Chinese Academy of Sciences, Shijingshan District, Beijing, People's Republic of China
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25
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Engrafted VHL peptide-delivered bone marrow stromal cells promote spinal cord repair in rats. Neuroreport 2010; 21:287-92. [PMID: 20125055 DOI: 10.1097/wnr.0b013e328336ee9a] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Stem cell-based therapy using bone marrow stromal cells (MSCs) has been expected to be a promising therapy for neuronal regeneration. To repair the injured spinal cord, neuronal differentiation of MSCs before transplantation has a more satisfactory effect. Recently, neuronal differentiation of neural progenitor/stem cells by an intracellular delivery of a pVHL-derived synthetic peptide (VHL peptide) has been shown. Here, we show that VHL peptide-delivered MSCs differentiated into neuron-like cells, and that engrafted VHL peptide-delivered MSCs more recovered the behaviors of the rats than that of nondelivered MSCs. Our result suggests that the use of VHL peptide-delivered MSCs would be a promising therapeutic strategy for repairing the injured spinal cord.
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Huang H, Chen L, Sanberg P. Cell Therapy From Bench to Bedside Translation in CNS Neurorestoratology Era. CELL MEDICINE 2010; 1:15-46. [PMID: 21359168 DOI: 10.3727/215517910x516673] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Recent advances in cell biology, neural injury and repair, and the progress towards development of neurorestorative interventions are the basis for increased optimism. Based on the complexity of the processes of demyelination and remyelination, degeneration and regeneration, damage and repair, functional loss and recovery, it would be expected that effective therapeutic approaches will require a combination of strategies encompassing neuroplasticity, immunomodulation, neuroprotection, neurorepair, neuroreplacement, and neuromodulation. Cell-based restorative treatment has become a new trend, and increasing data worldwide have strongly proven that it has a pivotal therapeutic value in CNS disease. Moreover, functional neurorestoration has been achieved to a certain extent in the CNS clinically. Up to now, the cells successfully used in preclinical experiments and/or clinical trial/treatment include fetal/embryonic brain and spinal cord tissue, stem cells (embryonic stem cells, neural stem/progenitor cells, hematopoietic stem cells, adipose-derived adult stem/precursor cells, skin-derived precursor, induced pluripotent stem cells), glial cells (Schwann cells, oligodendrocyte, olfactory ensheathing cells, astrocytes, microglia, tanycytes), neuronal cells (various phenotypic neurons and Purkinje cells), mesenchymal stromal cells originating from bone marrow, umbilical cord, and umbilical cord blood, epithelial cells derived from the layer of retina and amnion, menstrual blood-derived stem cells, Sertoli cells, and active macrophages, etc. Proof-of-concept indicates that we have now entered a new era in neurorestoratology.
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Affiliation(s)
- Hongyun Huang
- Center for Neurorestoratology, Beijing Rehabilitation Center, Beijing, P.R. China
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Hunt DPJ, Jahoda C, Chandran S. Multipotent skin-derived precursors: from biology to clinical translation. Curr Opin Biotechnol 2009; 20:522-30. [PMID: 19896826 DOI: 10.1016/j.copbio.2009.10.004] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2009] [Accepted: 10/09/2009] [Indexed: 01/17/2023]
Abstract
Skin-derived precursor cells (SKPs) are a novel population of neural crest-related precursor cells that can be isolated from embryonic and adult skin. SKPs are capable of generating neuronal, glial and mesodermal progeny. Fate mapping and microdissection experiments have demonstrated a neural crest origin of SKPs within defined niches in adult skin. The finding that SKP derivatives such as Schwann cells and neuronal cells have in vitro and in vivo function raises the possibility of SKPs being both an experimental and therapeutic resource for disease modelling and regenerative medicine. This review focuses on the increased understanding of the developmental and anatomical origins of SKPs and the biotechnological potential of these cells.
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Affiliation(s)
- David P J Hunt
- Euan MacDonald Centre, Centre for Clinical Brain Sciences, University of Edinburgh, Chancellors Building, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom.
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