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1دورية أكاديمية
المؤلفون: Mueller, Jessica, Stavely, Rhian, Guyer, Richard, Soos, Ádám, Bhave, Sukhada, Han, Chris, Hotta, Ryo, Nagy, Nandor, Goldstein, Allen
المصدر: Stem Cells Translational Medicine. 13(5)
مصطلحات موضوعية: Hirschsprung disease, enteric nervous system, enteric neuronal stem cells, extracellular matrix, stem cell therapy, Animals, Cell Movement, Neural Stem Cells, Mice, Agrin, Enteric Nervous System, Colon, Neural Crest, Hirschsprung Disease, Stem Cell Transplantation
الوصف: Regenerative cell therapy to replenish the missing neurons and glia in the aganglionic segment of Hirschsprung disease represents a promising treatment option. However, the success of cell therapies for this condition are hindered by poor migration of the transplanted cells. This limitation is in part due to a markedly less permissive extracellular environment in the postnatal gut than that of the embryo. Coordinated interactions between enteric neural crest-derived cells (ENCDCs) and their local environment drive migration along the embryonic gut during development of the enteric nervous system. Modifying transplanted cells, or the postnatal extracellular environment, to better recapitulate embryonic ENCDC migration could be leveraged to improve the engraftment and coverage of stem cell transplants. We compared the transcriptomes of ENCDCs from the embryonic intestine to that of postnatal-derived neurospheres and identified 89 extracellular matrix (ECM)-associated genes that are differentially expressed. Agrin, a heparin sulfate proteoglycan with a known inhibitory effect on ENCDC migration, was highly over-expressed by postnatal-derived neurospheres. Using a function-blocking antibody and a shRNA-expressing lentivirus, we show that inhibiting agrin promotes ENCDC migration in vitro and following cell transplantation ex vivo and in vivo. This enhanced migration is associated with an increased proportion of GFAP + cells, whose migration is especially enhanced.
وصف الملف: application/pdf
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2دورية أكاديمية
المؤلفون: Soto, Jennifer, Ding, Xili, Wang, Aijun, Li, Song
المصدر: Stem Cells Translational Medicine. 10(5)
مصطلحات موضوعية: Medical Biotechnology, Biomedical and Clinical Sciences, Engineering, Biomedical Engineering, Neurosciences, Dental/Oral and Craniofacial Disease, Stem Cell Research - Embryonic - Human, Regenerative Medicine, Stem Cell Research - Nonembryonic - Human, Stem Cell Research - Embryonic - Non-Human, Stem Cell Research, Pediatric, Stem Cell Research - Nonembryonic - Non-Human, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Neurological, Cell Differentiation, Cellular Reprogramming, Female, Humans, Neural Crest, Neural Stem Cells, Placenta, Pluripotent Stem Cells, Pregnancy, Regeneration, adult stem cells, disease modeling, neural crest stem cells, placental stem cells, regenerative medicine, Biochemistry and Cell Biology, Clinical Sciences, Medical biotechnology, Biomedical engineering
الوصف: Neural crest stem cells (NCSCs) are a transient population of cells that arise during early vertebrate development and harbor stem cell properties, such as self-renewal and multipotency. These cells form at the interface of non-neuronal ectoderm and neural tube and undergo extensive migration whereupon they contribute to a diverse array of cell and tissue derivatives, ranging from craniofacial tissues to cells of the peripheral nervous system. Neural crest-like stem cells (NCLSCs) can be derived from pluripotent stem cells, placental tissues, adult tissues, and somatic cell reprogramming. NCLSCs have a differentiation capability similar to NCSCs, and possess great potential for regenerative medicine applications. In this review, we present recent developments on the various approaches to derive NCLSCs and the therapeutic application of these cells for tissue regeneration.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/5r98v454Test
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3دورية أكاديمية
المؤلفون: Zoe M. Johnson, Yuan Yuan, Xiangjia Li, Tea Jashashvili, Michael Jamieson, Mark Urata, Yong Chen, Yang Chai
المصدر: Stem Cells Translational Medicine, Vol 10, Iss 8, Pp 1170-1183 (2021)
مصطلحات موضوعية: bone marrow aspirate, critical size defect, dental pulp neural crest cell, hydroxyapatite tricalcium phosphate, mesenchymal stem cells, Medicine (General), R5-920, Cytology, QH573-671
الوصف: Abstract Craniofacial bones protect vital organs, perform important physiological functions, and shape facial identity. Critical‐size defects (CSDs) in calvarial bones, which will not heal spontaneously, are caused by trauma, congenital defects, or tumor resections. They pose a great challenge for patients and physicians, and significantly compromise quality of life. Currently, calvarial CSDs are treated either by allogenic or autologous grafts, metal or other synthetic plates that are associated with considerable complications. While previous studies have explored tissue regeneration for calvarial defects, most have been done in small animal models with limited translational value. Here we define a swine calvarial CSD model and show a novel approach to regenerate high‐quality bone in these defects by combining mesenchymal stem cells (MSCs) with a three‐dimensional (3D)‐printed osteoconductive HA/TCP scaffold. Specifically, we have compared the performance of dental pulp neural crest MSCs (DPNCCs) to bone marrow aspirate (BMA) combined with a 3D‐printed HA/TCP scaffold to regenerate bone in a calvarial CSD (>7.0 cm2). Both DPNCCs and BMA loaded onto the 3D‐printed osteoconductive scaffold support the regeneration of calvarial bone with density, compression strength, and trabecular structures similar to native bone. Our study demonstrates a novel application of an original scaffold design combined with DPNCCs or BMA to support regeneration of high‐quality bone in a newly defined and clinically relevant swine calvarial CSD model. This discovery may have important impact on bone regeneration beyond the craniofacial region and will ultimately benefit patients who suffer from debilitating CSDs.
وصف الملف: electronic resource
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4دورية أكاديمية
المؤلفون: Huipu Yuan, Hui Hu, Rui Chen, Wenbo Mu, Liangliang Wang, Ying Li, Yuelei Chen, Xiaoyan Ding, Yongmei Xi, ShanShan Mao, Mizu Jiang, Jie Chen, Yong He, Lang Wang, Yi Dong, Jinfa Tou, Wei Chen
المصدر: Stem Cells Translational Medicine, Vol 10, Iss 6, Pp 922-938 (2021)
مصطلحات موضوعية: bowel motility, enteric neuroregeneration, premigratory neural crest stem cells, tissue engineered intestine, transplantation, Medicine (General), R5-920, Cytology, QH573-671
الوصف: Abstract Hirschsprung's disease (HSCR) is a common congenital defect. It occurs when bowel colonization by neural crest‐derived enteric nervous system (ENS) precursors is incomplete during the first trimester of pregnancy. Several sources of candidate cells have been previously studied for their capacity to regenerate the ENS, including enteric neural crest stem cells (En‐NCSCs) derived from native intestine or those simulated from human pluripotent stem cells (hPSCs). However, it is not yet known whether the native NCSCs other than En‐NCSCs would have the potential of regenerating functional enteric neurons and producing neuron dependent motility under the intestinal environment. The present study was designed to determine whether premigratory NCSCs (pNCSCs), as a type of the nonenteric NCSCs, could form enteric neurons and mediate the motility. pNCSCs were firstly transplanted into the colon of adult mice, and were found to survive, migrate, differentiate into enteric neurons, and successfully integrate into the adult mouse colon. When the mixture of pNCSCs and human intestinal organoids was implanted into the subrenal capsule of nude mice and grown into the mature tissue‐engineered intestine (TEI), the pNCSCs‐derived neurons mediated neuron‐dependent peristalsis of TEI. These results show that the pNCSCs that were previously assumed to not be induced by intestinal environment or cues can innervate the intestine and establish neuron‐dependent motility. Future cell candidates for ENS regeneration may include nonenteric NCSCs.
وصف الملف: electronic resource
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5دورية أكاديمية
المؤلفون: Juliane D. Glaeser, Phillip Behrens, Tina Stefanovic, Khosrowdad Salehi, Angela Papalamprou, Wafa Tawackoli, Melodie F. Metzger, Samuel Eberlein, Trevor Nelson, Yasaman Arabi, Kevin Kim, Robert H. Baloh, Shiran Ben‐David, Doron Cohn‐Schwartz, Robert Ryu, Hyun W. Bae, Zulma Gazit, Dmitriy Sheyn
المصدر: Stem Cells Translational Medicine, Vol 10, Iss 5, Pp 797-809 (2021)
مصطلحات موضوعية: allograft, bone healing, cranial repair, MSC, neural crest cells, Medicine (General), R5-920, Cytology, QH573-671
الوصف: Abstract Replacement of lost cranial bone (partly mesodermal and partly neural crest‐derived) is challenging and includes the use of nonviable allografts. To revitalize allografts, bone marrow‐derived mesenchymal stromal cells (mesoderm‐derived BM‐MSCs) have been used with limited success. We hypothesize that coating of allografts with induced neural crest cell‐mesenchymal progenitor cells (iNCC‐MPCs) improves implant‐to‐bone integration in mouse cranial defects. Human induced pluripotent stem cells were reprogramed from dermal fibroblasts, differentiated to iNCCs and then to iNCC‐MPCs. BM‐MSCs were used as reference. Cells were labeled with luciferase (Luc2) and characterized for MSC consensus markers expression, differentiation, and risk of cellular transformation. A calvarial defect was created in non‐obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and allografts were implanted, with or without cell coating. Bioluminescence imaging (BLI), microcomputed tomography (μCT), histology, immunofluorescence, and biomechanical tests were performed. Characterization of iNCC‐MPC‐Luc2 vs BM‐MSC‐Luc2 showed no difference in MSC markers expression and differentiation in vitro. In vivo, BLI indicated survival of both cell types for at least 8 weeks. At week 8, μCT analysis showed enhanced structural parameters in the iNCC‐MPC‐Luc2 group and increased bone volume in the BM‐MSC‐Luc2 group compared to controls. Histology demonstrated improved integration of iNCC‐MPC‐Luc2 allografts compared to BM‐MSC‐Luc2 group and controls. Human osteocalcin and collagen type 1 were detected at the allograft‐host interphase in cell‐seeded groups. The iNCC‐MPC‐Luc2 group also demonstrated improved biomechanical properties compared to BM‐MSC‐Luc2 implants and cell‐free controls. Our results show an improved integration of iNCC‐MPC‐Luc2‐coated allografts compared to BM‐MSC‐Luc2 and controls, suggesting the use of iNCC‐MPCs as potential cell source for cranial bone repair.
وصف الملف: electronic resource
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6دورية أكاديمية
المؤلفون: Jennifer Soto, Xili Ding, Aijun Wang, Song Li
المصدر: Stem Cells Translational Medicine, Vol 10, Iss 5, Pp 681-693 (2021)
مصطلحات موضوعية: adult stem cells, disease modeling, neural crest stem cells, placental stem cells, regenerative medicine, Medicine (General), R5-920, Cytology, QH573-671
الوصف: Abstract Neural crest stem cells (NCSCs) are a transient population of cells that arise during early vertebrate development and harbor stem cell properties, such as self‐renewal and multipotency. These cells form at the interface of non‐neuronal ectoderm and neural tube and undergo extensive migration whereupon they contribute to a diverse array of cell and tissue derivatives, ranging from craniofacial tissues to cells of the peripheral nervous system. Neural crest‐like stem cells (NCLSCs) can be derived from pluripotent stem cells, placental tissues, adult tissues, and somatic cell reprogramming. NCLSCs have a differentiation capability similar to NCSCs, and possess great potential for regenerative medicine applications. In this review, we present recent developments on the various approaches to derive NCLSCs and the therapeutic application of these cells for tissue regeneration.
وصف الملف: electronic resource
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7دورية أكاديمية
المؤلفون: McMahill, Barbara G, Spriet, Mathieu, Sisó, Sílvia, Manzer, Michael D, Mitchell, Gaela, McGee, Jeannine, Garcia, Tanya C, Borjesson, Dori L, Sieber-Blum, Maya, Nolta, Jan A, Sturges, Beverly K
المصدر: Stem cells translational medicine. 4(10)
مصطلحات موضوعية: Spinal Cord, Neural Crest, Animals, Mice, Knockout, Dogs, Mice, Teratoma, Magnetic Resonance Imaging, Gait, Walking, Stem Cell Transplantation, Injections, Spinal, Feasibility Studies, Pilot Projects, Behavior, Animal, Cell Survival, Neurogenesis, Neural Stem Cells, Epidermal Cells, Adult stem cells, Canine epidermal neural crest stem cell, Canine epidermal neural crest stem cells, Dog model, Epidermal neural crest stem cell, Spinal cord injury, Neurodegenerative, Spinal Cord Injury, Regenerative Medicine, Traumatic Head and Spine Injury, Transplantation, Physical Injury - Accidents and Adverse Effects, Pediatric, Stem Cell Research - Nonembryonic - Non-Human, Neurosciences, Stem Cell Research - Nonembryonic - Human, Stem Cell Research, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Neurological, Biochemistry and Cell Biology, Medical Biotechnology, Clinical Sciences
الوصف: UnlabelledThis pilot feasibility study aimed to determine the outcome of canine epidermal neural crest stem cell (cEPI-NCSC) grafts in the normal spinal cords of healthy bred-for-research dogs. This included developing novel protocols for (a) the ex vivo expansion of cEPI-NCSCs, (b) the delivery of cEPI-NCSCs into the spinal cord, and (c) the labeling of the cells and subsequent tracing of the graft in the live animal by magnetic resonance imaging. A total of four million cEPI-NCSCs were injected into the spinal cord divided in two locations. Differences in locomotion at baseline and post-treatment were evaluated by gait analysis and compared with neurological outcome and behavioral exams. Histopathological analyses of the spinal cords and cEPI-NCSC grafts were performed at 3 weeks post-transplantation. Neurological and gait parameters were minimally affected by the stem cell injection. cEPI-NCSCs survived in the canine spinal cord for the entire period of investigation and did not migrate or proliferate. Subsets of cEPI-NCSCs expressed the neural crest stem cell marker Sox10. There was no detectable expression of markers for glial cells or neurons. The tissue reaction to the cell graft was predominantly vascular in addition to a degree of reactive astrogliosis and microglial activation. In the present study, we demonstrated that cEPI-NCSC grafts survive in the spinal cords of healthy dogs without major adverse effects. They persist locally in the normal spinal cord, may promote angiogenesis and tissue remodeling, and elicit a tissue response that may be beneficial in patients with spinal cord injury.SignificanceIt has been established that mouse and human epidermal neural crest stem cells are somatic multipotent stem cells with proved innovative potential in a mouse model of spinal cord injury (SCI) offering promise of a valid treatment for SCI. Traumatic SCI is a common neurological problem in dogs with marked similarities, clinically and pathologically, to the syndrome in people. For this reason, dogs provide a readily accessible, clinically realistic, spontaneous model for evaluation of epidermal neural crest stem cells therapeutic intervention. The results of this study are expected to give the baseline data for a future clinical trial in dogs with traumatic SCI.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/4tp7g7jdTest
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8دورية أكاديمية
المؤلفون: Johanna Diener, Lukas Sommer
المصدر: Stem Cells Translational Medicine, Vol 10, Iss 4, Pp 522-533 (2021)
مصطلحات موضوعية: cancer, development, drug resistance, invasion, melanoma, neural crest stem cells (NCSCs), Medicine (General), R5-920, Cytology, QH573-671
الوصف: Abstract Melanoma is the deadliest of all skin cancers due to its high metastatic potential. In recent years, advances in targeted therapy and immunotherapy have contributed to a remarkable progress in the treatment of metastatic disease. However, intrinsic or acquired resistance to such therapies remains a major obstacle in melanoma treatment. Melanoma disease progression, beginning from tumor initiation and growth to acquisition of invasive phenotypes and metastatic spread and acquisition of treatment resistance, has been associated with cellular dedifferentiation and the hijacking of gene regulatory networks reminiscent of the neural crest (NC)—the developmental structure which gives rise to melanocytes and hence melanoma. This review summarizes the experimental evidence for the involvement of NC stem cell (NCSC)‐like cell states during melanoma progression and addresses novel approaches to combat the emergence of stemness characteristics that have shown to be linked with aggressive disease outcome and drug resistance.
وصف الملف: electronic resource
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9دورية أكاديمية
المصدر: Stem Cells Translational Medicine, Vol 9, Iss 11, Pp 1462-1476 (2020)
مصطلحات موضوعية: autologous, cellular therapy, clinical translation, neural crest‐derived stem cells, neural induction, serum‐free media, Medicine (General), R5-920, Cytology, QH573-671
الوصف: Abstract The potential of obtaining cell cultures with neural crest resemblance (neural crest‐derived stem cells [NCSCs]) from dental‐related tissues, including human dental pulp cells (hDPCs), has been discussed in the literature. However, most reports include the use of serum‐rich conditions and do not describe the potential for neural differentiation, slowing translation to the clinic. Therefore, we aimed to culture and characterize NCSCs from the human dental pulp in vitro and evaluate their ability to differentiate into neurons; we also investigated the effectiveness of the addition of BMP4 to enhance this potential. Cultures were established from a varied cohort of patient samples and grown, as monolayers, in serum, serum‐free, and also under sphere‐aggregation conditions to induce and identify a NCSC phenotype. hDPC cultures were characterized by immunocytochemistry and reverse transcription quantitative polymerase chain reaction. Monolayer cultures expressed stem cell, neural progenitor and neural crest‐related markers. Culturing hDPCs as neurospheres (hDPC‐NCSCs) resulted in an increased expression of neural crest‐related genes, while the addition of BMP4 appeared to produce better NCSC characteristics and neural differentiation. The neural‐like phenotype was evidenced by the expression of TUJ1, peripherin, NFH, TAU, SYN1, and GAP43. Our results describe the establishment of hDPC cultures from a large variety of patients in serum‐free medium, as NCSC that differentiate into neural‐like cells, as well as an important effect of BMP4 in enhancing the neural crest phenotype and differentiation of hDPCs.
وصف الملف: electronic resource
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10دورية أكاديمية
المؤلفون: Gericota, Barbara, Anderson, Joseph S, Mitchell, Gaela, Borjesson, Dori L, Sturges, Beverly K, Nolta, Jan A, Sieber-Blum, Maya
المصدر: Stem cells translational medicine. 3(3)
مصطلحات موضوعية: Spinal Cord, Hair Follicle, Multipotent Stem Cells, Neural Crest, Animals, Dogs, Humans, Mice, Spinal Cord Injuries, Disease Models, Animal, Proto-Oncogene Proteins c-myc, Cell Separation, Cell Proliferation, Gene Expression, Female, Male, Octamer Transcription Factor-3, Kruppel-Like Transcription Factors, SOXB1 Transcription Factors, Neural Stem Cells, Cell- and Tissue-Based Therapy, Biomarkers, Adult stem cells, Canine epidermal neural crest stem cells, Dog model, EPI-NCSC, Hair follicle, Neural crest, Spinal cord injury, cEPI-NCSC, Kruppel-Like Factor 4, Spinal Cord Injury, Stem Cell Research - Nonembryonic - Human, Regenerative Medicine, Stem Cell Research, Traumatic Head and Spine Injury, Neurodegenerative, Physical Injury - Accidents and Adverse Effects, Neurosciences, Stem Cell Research - Nonembryonic - Non-Human, Pediatric, 5.2 Cellular and gene therapies, Development of treatments and therapeutic interventions, Neurological, Biochemistry and Cell Biology, Medical Biotechnology, Clinical Sciences
الوصف: The discovery of multipotent neural crest-derived stem cells, named epidermal neural crest stem cells (EPI-NCSC), that persist postnatally in an easy-to-access location-the bulge of hair follicles-opens a spectrum of novel opportunities for patient-specific therapies. We present a detailed characterization of canine EPI-NCSC (cEPI-NCSC) from multiple dog breeds and protocols for their isolation and ex vivo expansion. Furthermore, we provide novel tools for research in canines, which currently are still scarce. In analogy to human and mouse EPI-NCSC, the neural crest origin of cEPI-NCSC is shown by their expression of the neural crest stem cell molecular signature and other neural crest-characteristic genes. Similar to human EPI-NCSC, cEPI-NCSC also expressed pluripotency genes. We demonstrated that cEPI-NCSC can generate all major neural crest derivatives. In vitro clonal analyses established multipotency and self-renewal ability of cEPI-NCSC, establishing cEPI-NCSC as multipotent somatic stem cells. A critical analysis of the literature on canine spinal cord injury (SCI) showed the need for novel treatments and suggested that cEPI-NCSC represent viable candidates for cell-based therapies in dog SCI, particularly for chondrodystrophic dogs. This notion is supported by the close ontological relationship between neural crest stem cells and spinal cord stem cells. Thus, cEPI-NCSC promise to offer not only a potential treatment for canines but also an attractive and realistic large animal model for human SCI. Taken together, we provide the groundwork for the development of a novel cell-based therapy for a condition with extremely poor prognosis and no available effective treatment.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/9g1323f9Test
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