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Melitta Schachner - One of the best experts on this subject based on the ideXlab platform.

  • Knockdown of chondroitin-4-sulfotransferase-1, but not of dermatan-4-sulfotransferase-1, accelerates Regeneration of zebrafish after Spinal Cord injury.
    The FASEB Journal, 2018
    Co-Authors: Sudhanshu Sahu, Gabriele Loers, Melitta Schachner
    Abstract:

    Glycosaminoglycans such as chondroitin sulfate (CS) and dermatan sulfate (DS) are long chains of repeating disaccharide units, covalently linked to core proteins to form proteoglycans. Proteoglycans can be cell membrane-bound or are part of the extracellular matrix. They are important in a wide range of biologic processes, including development, synaptic plasticity, and Regeneration after injury, as well as modulation of growth factor signaling, cell migration, survival, and proliferation. Synthesis of CS and DS in the Golgi apparatus is mediated by sulfotransferases that modify sugar chains through transfer of sulfate groups to specific positions on the sugar moieties. To clarify the functions of CS and DS during nervous system Regeneration, we studied the effect of chondroitin 4- O-sulfotransferase-1/carbohydrate sulfotransferase-11 (C4ST-1/Chst-11) and dermatan 4- O-sulfotransferase-1/Chst-14 (D4ST-1/Chst-14) down-regulation on Spinal Cord Regeneration in larval and adult zebrafish. In our study, knockdown of C4ST1/Chst-11 accelerated Regeneration after Spinal Cord injury in larval and adult zebrafish and knockdown of D4ST1/Chst-14 did not alter regenerative capacity. From these and previous observations, we drew the conclusion that different CS and DS expression patterns can be growth permitting, growth inhibiting, or neutral for regrowing or sprouting axons, depending on the tissue environment of a particular animal species.-Sahu, S., Li, R., Loers, G., Schachner, M. Knockdown of chondroitin-4-sulfotransferase-1, but not of dermatan-4-sulfotransferase-1, accelerates Regeneration of zebrafish after Spinal Cord injury.

  • the cell neural adhesion molecule contactin 2 tag 1 is beneficial for functional recovery after Spinal Cord injury in adult zebrafish
    PLOS ONE, 2012
    Co-Authors: Jinfei Lin, Melitta Schachner, Hongchao Pan, Yanqin Shen
    Abstract:

    The cell neural adhesion molecule contactin-2 plays a key role in axon extension and guidance, fasciculation, and myelination during development. We thus asked, whether contactin-2 is also important in nervous system Regeneration after trauma. In this study, we used an adult zebrafish Spinal Cord transection model to test the functions of contactin-2 in Spinal Cord Regeneration. The expression patterns of contactin-2 at different time points after Spinal Cord injury were studied at the mRNA level by qPCR and in situ hybridization, and contactin-2 protein levels and immunohistological localization were detected by Western blot and immunofluorescence analyses, respectively. Contactin-2 mRNA and protein levels were increased along the central canal at 6 days and 11 days after Spinal Cord injury, suggesting a requirement for contactin-2 in Spinal Cord Regeneration. Co-localization of contactin-2 and islet-1 (a motoneuron marker) was observed in Spinal Cords before and after injury. To further explore the functions of contactin-2 in Regeneration, an anti-sense morpholino was used to knock down the expression of contactin-2 protein by application at the time of injury. Motion analysis showed that inhibition of contactin-2 retarded the recovery of swimming functions when compared to standard control morpholino. Anterograde and retrograde tracing at 6 weeks after injury showed that knock down of contactin-2 inhibited axonal regrowth from NMLF neurons beyond lesion site. The combined observations indicate that contactin-2 contributes to locomotor recovery and successful regrowth of axons after Spinal Cord injury in adult zebrafish.

  • the extracellular matrix glycoprotein tenascin c promotes locomotor recovery after Spinal Cord injury in adult zebrafish
    Neuroscience, 2011
    Co-Authors: Massimiliano Cristofanilli, A Valiveti, M Yoo, F Morellini, Melitta Schachner
    Abstract:

    Adult zebrafish, by virtue of exhibiting spontaneous recovery after Spinal lesion, have evolved into a paradigmatic vertebrate model system to identify novel genes vital for successful Regeneration after Spinal Cord injury. Due to a remarkable level of conservation between zebrafish and human genomes, such genes, once identified, could point to possibilities for addressing the multiple issues on how to deal with functional recovery after Spinal Cord injury in humans. In the current study, the extracellular matrix glycoprotein tenascin-C was studied in the zebrafish Spinal Cord injury model to assess the often disparate functions of this multidomain molecule under in vivo conditions. This in vivo study was deemed necessary since in vitro studies had shown discrepant functional effects on neurite outgrowth: tenascin-C inhibits neurite outgrowth when presented as a molecular barrier adjacent to a conducive substrate, but enhances neurite outgrowth when presented as a uniform substrate. Thus, our current study addresses the question as to which of these features prevails in vivo: whether tenascin-C reduces or enhances axonal regrowth after injury in a well accepted vertebrate model of Spinal Cord injury. We show upregulation of tenascin-C expression in regenerating neurons of the nucleus of median longitudinal fascicle (NMLF) in the brainstem and Spinal motoneurons. Inhibition of tenascin-C expression by antisense oligonucleotide (morpholino) resulted in impaired locomotor recovery, reduced regrowth of axons from brainstem neurons and reduced synapse formation by the regrowing brainstem axons on Spinal motoneurons, all vital indicators of Regeneration. Our results thus point to an advantageous role of tenascin-C in promoting Spinal Cord Regeneration, by promoting axonal regrowth and synapse formation in the Spinal Cord caudal to the lesion site after injury.

  • embryonic stem cell derived l1 overexpressing neural aggregates enhance recovery after Spinal Cord injury in mice
    PLOS ONE, 2011
    Co-Authors: Melitta Schachner, Yi Fang Cui, Gunnar Hargus, Igor Jakovcevski, Christian Bernreuther
    Abstract:

    An obstacle to early stem cell transplantation into the acutely injured Spinal Cord is poor survival of transplanted cells. Transplantation of embryonic stem cells as substrate adherent embryonic stem cell-derived neural aggregates (SENAs) consisting mainly of neurons and radial glial cells has been shown to enhance survival of grafted cells in the injured mouse brain. In the attempt to promote the beneficial function of these SENAs, murine embryonic stem cells constitutively overexpressing the neural cell adhesion molecule L1 which favors axonal growth and survival of grafted and imperiled cells in the inhibitory environment of the adult mammalian central nervous system were differentiated into SENAs and transplanted into the Spinal Cord three days after compression lesion. Mice transplanted with L1 overexpressing SENAs showed improved locomotor function when compared to mice injected with wild-type SENAs. L1 overexpressing SENAs showed an increased number of surviving cells, enhanced neuronal differentiation and reduced glial differentiation after transplantation when compared to SENAs not engineered to overexpress L1. Furthermore, L1 overexpressing SENAs rescued imperiled host motoneurons and parvalbumin-positive interneurons and increased numbers of catecholaminergic nerve fibers distal to the lesion. In addition to encouraging the use of embryonic stem cells for early therapy after Spinal Cord injury L1 overexpression in the microenvironment of the lesioned Spinal Cord is a novel finding in its functions that would make it more attractive for pre-clinical studies in Spinal Cord Regeneration and most likely other diseases of the nervous system.

  • transcription factor sox11b is involved in Spinal Cord Regeneration in adult zebrafish
    Neuroscience, 2011
    Co-Authors: Yuji Guo, Massimiliano Cristofanilli, Ronald P Hart, Aijun Hao, Melitta Schachner
    Abstract:

    Adult zebrafish have the ability to recover from Spinal Cord injury and exhibit re-growth of descending axons from the brainstem to the Spinal Cord. We performed gene expression analysis using microarray to find damage-induced genes after Spinal Cord injury, and found that Sox11b mRNA is up-regulated at 11 days after injury. However, the functional relevance of Sox11b for Regeneration is not known. Here, we report that the up-regulation of Sox11b mRNA after Spinal Cord injury is mainly localized in ependymal cells lining the central canal and in newly differentiating neuronal precursors or immature neurons. Using an in vivo morpholino-based gene knockout approach, we demonstrate that Sox11b is essential for locomotor recovery after Spinal Cord injury. In the injured Spinal Cord, expression of the neural stem cell associated gene Nestin, and the proneural gene Ascl1a (Mash1a), which are involved in the self-renewal and cell fate specification of endogenous neural stem cells, respectively, is regulated by Sox11b. Our data indicate that Sox11b promotes neuronal determination of endogenous stem cells and regenerative neurogenesis following Spinal Cord injury in the adult zebrafish. Enhancing Sox11b expression to promote proliferation and neurogenic determination of endogenous neural stem cells after injury may be a promising strategy in restorative therapy after Spinal Cord injury in mammals.

Yasuyuki Amoh - One of the best experts on this subject based on the ideXlab platform.

  • from hair to heart nestin expressing hair follicle associated pluripotent hap stem cells differentiate to beating cardiac muscle cells
    Journal of Dermatological Science, 2016
    Co-Authors: Masateru Yashiro, Robert M. Hoffman, Yuko Hamada, Katsumasa Kawahara, Ryoichi Aki, Nobuko Arakawa, Sumiyuki Mii, Yasuyuki Amoh
    Abstract:

    We have previously demonstrated that the neural stem-cell marker nestin is expressed in hair follicle stem cells located in the bulge area which are termed hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells from mouse and human could form spheres in culture, termed hair spheres, which are keratin 15-negative and CD34-positive and could differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we demonstrated that nestin-expressing stem cells could effect nerve and Spinal Cord Regeneration in mouse models. In the present study, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. We separated the mouse vibrissa hair follicle into 3 parts (upper, middle, and lower), and suspended each part separately in DMEM containing 10% FBS. All three parts of hair follicle differentiated to beating cardiac muscle cells as well as neurons, glial cells, keratinocytes and smooth muscle cells. The differentiation potential to cardiac muscle is greatest in the upper part of the follicle. The beat rate of the cardiac muscle cells was stimulated by isoproterenol and inhibited by propanolol. HAP stem cells have potential for regenerative medicine for heart disease as well as nerve and Spinal Cord repair.

  • isoproterenol directs hair follicle associated pluripotent hap stem cells to differentiate in vitro to cardiac muscle cells which can be induced to form beating heart muscle tissue sheets
    Cell Cycle, 2016
    Co-Authors: Aiko Yamazaki, Robert M. Hoffman, Yuko Hamada, Katsumasa Kawahara, Masateru Yashiro, Nobuko Arakawa, Yasuyuki Amoh
    Abstract:

    ABSTRACTNestin-expressing hair-follicle-associated pluripotent (HAP) stem cells are located in the bulge area of the follicle. Previous studies have shown that HAP stem cells can differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. HAP stem cells effected nerve and Spinal Cord Regeneration in mouse models. Recently, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. The differentiation potential to cardiac muscle cells was greatest in the upper part of the follicle. The beat rate of the cardiac muscle cells was stimulated by isoproterenol. In the present study, we observed that isoproterenol directs HAP stem cells to differentiate to cardiac muscle cells in large numbers in culture compared to HAP stem cells not supplemented with isoproterenol. The addition of activin A, bone morphogenetic protein 4, and basic fibroblast growth factor, along with isoproternal, induced the cardiac muscle cells to form tissue sheets of beating heart m...

  • from hair to heart nestin expressing hair follicle associated pluripotent hap stem cells differentiate to beating cardiac muscle cells
    Cell Cycle, 2015
    Co-Authors: Masateru Yashiro, Robert M. Hoffman, Yuko Hamada, Katsumasa Kawahara, Nobuko Arakawa, Yasuyuki Amoh
    Abstract:

    We have previously demonstrated that the neural stem-cell marker nestin is expressed in hair follicle stem cells located in the bulge area which are termed hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells from mouse and human could form spheres in culture, termed hair spheres, which are keratin 15-negative and CD34-positive and could differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we demonstrated that nestin-expressing stem cells could effect nerve and Spinal Cord Regeneration in mouse models. In the present study, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. We separated the mouse vibrissa hair follicle into 3 parts (upper, middle, and lower), and suspended each part separately in DMEM containing 10% FBS. All three parts of hair follicle differentiated to beating cardiac muscle cells as well as neurons, glial cells, keratinocytes and smooth muscle cells. The differentiation potential to...

  • human hair follicle pluripotent stem hfps cells promote Regeneration of peripheral nerve injury an advantageous alternative to es and ips cells
    Journal of Cellular Biochemistry, 2009
    Co-Authors: Yasuyuki Amoh, Robert M. Hoffman, Maho Kanoh, Shiro Niiyama, Yuko Hamada, Katsumasa Kawahara, Yuichi Sato, Kensei Katsuoka
    Abstract:

    The optimal source of stem cells for regenerative medicine is a major question. Embryonic stem (ES) cells have shown promise for pluripotency but have ethical issues and potential to form teratomas. Pluripotent stem cells have been produced from skin cells by either viral-, plasmid- or transposon-mediated gene transfer. These stem cells have been termed induced pluripotent stem cells or iPS cells. iPS cells may also have malignant potential and are inefficiently produced. Embryonic stem cells may not be suited for individualized therapy, since they can undergo immunologic rejection. To address these fundamental problems, our group is developing hair follicle pluripotent stem (hfPS) cells. Our previous studies have shown that mouse hfPS cells can differentiate to neurons, glial cells in vitro, and other cell types, and can promote nerve and Spinal Cord Regeneration in vivo. hfPS cells are located above the hair follicle bulge in what we have termed the hfPS cell area (hfPSA) and are nestin positive and keratin 15 (K-15) negative. Human hfPS cells can also differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. In the present study, human hfPS cells were transplanted in the severed sciatic nerve of the mouse where they differentiated into glial fibrillary-acidic-protein (GFAP)-positive Schwann cells and promoted the recovery of pre-existing axons, leading to nerve generation. The regenerated nerve recovered function and, upon electrical stimulation, contracted the gastrocnemius muscle. The hfPS cells can be readily isolated from the human scalp, thereby providing an accessible, autologous and safe source of stem cells for regenerative medicine that have important advantages over ES or iPS cells.

Karen Echeverri - One of the best experts on this subject based on the ideXlab platform.

  • ap 1cfos junb mir 200a regulate the pro regenerative glial cell response during axolotl Spinal Cord Regeneration
    Communications biology, 2019
    Co-Authors: Peng Jiang, Micah D. Gearhart, Ron Stewart, Karen Echeverri, Keith Sabin
    Abstract:

    Salamanders have the remarkable ability to functionally regenerate after Spinal Cord transection. In response to injury, GFAP+ glial cells in the axolotl Spinal Cord proliferate and migrate to replace the missing neural tube and create a permissive environment for axon Regeneration. Molecular pathways that regulate the pro-regenerative axolotl glial cell response are poorly understood. Here we show axolotl glial cells up-regulate AP-1cFos/JunB after injury, which promotes a pro-regenerative glial cell response. Injury induced upregulation of miR-200a in glial cells supresses c-Jun expression in these cells. Inhibition of miR-200a during Regeneration causes defects in axonal regrowth and transcriptomic analysis revealed that miR-200a inhibition leads to differential regulation of genes involved with reactive gliosis, the glial scar, extracellular matrix remodeling and axon guidance. This work identifies a unique role for miR-200a in inhibiting reactive gliosis in axolotl glial cells during Spinal Cord Regeneration.

  • AP-1cFos/JunB/miR-200a regulate the pro-regenerative glial cell response during axolotl Spinal Cord Regeneration
    Nature Publishing Group, 2019
    Co-Authors: Keith Z. Sabin, Peng Jiang, Micah D. Gearhart, Ron Stewart, Karen Echeverri
    Abstract:

    Keith Sabin et al. showed that upregulation of the AP-1 complex, composed of c-Fos and JunB, in the axolotl Spinal Cord promotes a pro-regenerative glial cell response. This response is impaired by inhibition of miR-200a; suggesting an important role for this microRNA in axolotl Spinal Cord Regeneration

  • dynamic membrane depolarization is an early regulator of ependymoglial cell response to Spinal Cord injury in axolotl
    Developmental Biology, 2015
    Co-Authors: Keith Sabin, Tiago Santosferreira, Jaclyn Essig, Sarah E Rudasill, Karen Echeverri
    Abstract:

    Abstract Salamanders, such as the Mexican axolotl, are some of the few vertebrates fortunate in their ability to regenerate diverse structures after injury. Unlike mammals they are able to regenerate a fully functional Spinal Cord after injury. However, the molecular circuitry required to initiate a pro-regenerative response after Spinal Cord injury is not well understood. To address this question we developed a Spinal Cord injury model in axolotls and used in vivo imaging of labeled ependymoglial cells to characterize the response of these cells to injury. Using in vivo imaging of ion sensitive dyes we identified that Spinal Cord injury induces a rapid and dynamic change in the resting membrane potential of ependymoglial cells. Prolonged depolarization of ependymoglial cells after injury inhibits ependymoglial cell proliferation and subsequent axon Regeneration. Using transcriptional profiling we identified c-Fos as a key voltage sensitive early response gene that is expressed specifically in the ependymoglial cells after injury. This data establishes that dynamic changes in the membrane potential after injury are essential for regulating the specific spatiotemporal expression of c-Fos that is critical for promoting faithful Spinal Cord Regeneration in axolotl.

  • Spinal Cord Regeneration where fish frogs and salamanders lead the way can we follow
    Biochemical Journal, 2013
    Co-Authors: Juan Felipe Diaz Quiroz, Karen Echeverri
    Abstract:

    Major trauma to the mammalian Spinal Cord often results in irreversible loss of function, i.e. paralysis, and current therapies ranging from drugs, implantations of stem cells and/or biomaterials, and electrically stimulated nerve regrowth, have so far offered very limited success in improving quality-of-life. However, in marked contrast with this basic shortcoming of ours, certain vertebrate species, including fish and salamanders, display the amazing ability to faithfully regenerate various complex body structures after injury or ablation, restoring full functionality, even in the case of the Spinal Cord. Despite the inherently strong and obvious translational potential for improving treatment strategies for human patients, our in-depth molecular-level understanding of these decidedly more advanced repair systems remains in its infancy. In the present review, we will discuss the current state of this field, focusing on recent progress in such molecular analyses using various regenerative species, and how these so far relate to the mammalian situation.

Kyung Sun - One of the best experts on this subject based on the ideXlab platform.

  • nerve Regeneration following Spinal Cord injury using matrix metalloproteinase sensitive hyaluronic acid based biomimetic hydrogel scaffold containing brain derived neurotrophic factor
    Journal of Biomedical Materials Research Part A, 2009
    Co-Authors: Jonghyuck Park, Eunjeong Lim, Seung Keun Back, Yongdoo Park, Kyung Sun
    Abstract:

    Spinal Cord injury leads to the permanent loss of motor and sensory function in the body. To enhance Spinal Cord Regeneration, we used a hyaluronic acid-based hydrogel as a three-dimensional biomimetic scaffold for peptides and growth factors. Three components were used to provide guidance cues: a matrix metalloproteinase peptide crosslinker, an IKVAV (Ile- Lys-Val-Ala-Val) peptide derived from laminin, and brain-derived neurotrophic factor (BDNF). Human mesenchymal stem cells (hMSCs) were cultured in hydrogels in vitro for 10 days to induce neuronal differentiation of hMSCs. Based on gene-expression data, the matrix metalloproteinase-sensitive peptide, IKVAV peptide, and BDNF were critical in the differentiation of hMSCs. Remodeling activity was found to be a key factor in guiding neural differentiation of stem cells. To test this approach in vivo, we used the Spinal Cord injured rat model and five different hydrogel compositions. Samples were injected into the intrathecal space, and animals were monitored for 6 weeks. Compared to all other groups, animals injected with BDNF-containing hydrogels showed the greatest improvement on locomotive tests (Basso-Beattie-Bresnahan score) during the initial stage after injury. These results suggest that hyaluronic acid-based hydrogels containing IKVAV and BDNF create microenvironments that foster differentiation of stem cells along the neural cell lineage, and they could be used to facilitate nerve Regeneration after Spinal Cord injury.

  • nerve Regeneration following Spinal Cord injury using matrix metalloproteinase sensitive hyaluronic acid based biomimetic hydrogel scaffold containing brain derived neurotrophic factor
    Journal of Biomedical Materials Research Part A, 2009
    Co-Authors: Jonghyuck Park, Eunjeong Lim, Seung Keun Back, Yongdoo Park, Kyung Sun
    Abstract:

    Spinal Cord injury leads to the permanent loss of motor and sensory function in the body. To enhance Spinal Cord Regeneration, we used a hyaluronic acid-based hydrogel as a three-dimensional biomimetic scaffold for peptides and growth factors. Three components were used to provide guidance cues: a matrix metalloproteinase peptide crosslinker, an IKVAV (Ile- Lys-Val-Ala-Val) peptide derived from laminin, and brain-derived neurotrophic factor (BDNF). Human mesenchymal stem cells (hMSCs) were cultured in hydrogels in vitro for 10 days to induce neuronal differentiation of hMSCs. Based on gene-expression data, the matrix metalloproteinase-sensitive peptide, IKVAV peptide, and BDNF were critical in the differentiation of hMSCs. Remodeling activity was found to be a key factor in guiding neural differentiation of stem cells. To test this approach in vivo, we used the Spinal Cord injured rat model and five different hydrogel compositions. Samples were injected into the intrathecal space, and animals were monitored for 6 weeks. Compared to all other groups, animals injected with BDNF-containing hydrogels showed the greatest improvement on locomotive tests (Basso–Beattie–Bresnahan score) during the initial stage after injury. These results suggest that hyaluronic acid-based hydrogels containing IKVAV and BDNF create microenvironments that foster differentiation of stem cells along the neural cell lineage, and they could be used to facilitate nerve Regeneration after Spinal Cord injury. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010

Masateru Yashiro - One of the best experts on this subject based on the ideXlab platform.

  • from hair to heart nestin expressing hair follicle associated pluripotent hap stem cells differentiate to beating cardiac muscle cells
    Journal of Dermatological Science, 2016
    Co-Authors: Masateru Yashiro, Robert M. Hoffman, Yuko Hamada, Katsumasa Kawahara, Ryoichi Aki, Nobuko Arakawa, Sumiyuki Mii, Yasuyuki Amoh
    Abstract:

    We have previously demonstrated that the neural stem-cell marker nestin is expressed in hair follicle stem cells located in the bulge area which are termed hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells from mouse and human could form spheres in culture, termed hair spheres, which are keratin 15-negative and CD34-positive and could differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we demonstrated that nestin-expressing stem cells could effect nerve and Spinal Cord Regeneration in mouse models. In the present study, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. We separated the mouse vibrissa hair follicle into 3 parts (upper, middle, and lower), and suspended each part separately in DMEM containing 10% FBS. All three parts of hair follicle differentiated to beating cardiac muscle cells as well as neurons, glial cells, keratinocytes and smooth muscle cells. The differentiation potential to cardiac muscle is greatest in the upper part of the follicle. The beat rate of the cardiac muscle cells was stimulated by isoproterenol and inhibited by propanolol. HAP stem cells have potential for regenerative medicine for heart disease as well as nerve and Spinal Cord repair.

  • isoproterenol directs hair follicle associated pluripotent hap stem cells to differentiate in vitro to cardiac muscle cells which can be induced to form beating heart muscle tissue sheets
    Cell Cycle, 2016
    Co-Authors: Aiko Yamazaki, Robert M. Hoffman, Yuko Hamada, Katsumasa Kawahara, Masateru Yashiro, Nobuko Arakawa, Yasuyuki Amoh
    Abstract:

    ABSTRACTNestin-expressing hair-follicle-associated pluripotent (HAP) stem cells are located in the bulge area of the follicle. Previous studies have shown that HAP stem cells can differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. HAP stem cells effected nerve and Spinal Cord Regeneration in mouse models. Recently, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. The differentiation potential to cardiac muscle cells was greatest in the upper part of the follicle. The beat rate of the cardiac muscle cells was stimulated by isoproterenol. In the present study, we observed that isoproterenol directs HAP stem cells to differentiate to cardiac muscle cells in large numbers in culture compared to HAP stem cells not supplemented with isoproterenol. The addition of activin A, bone morphogenetic protein 4, and basic fibroblast growth factor, along with isoproternal, induced the cardiac muscle cells to form tissue sheets of beating heart m...

  • from hair to heart nestin expressing hair follicle associated pluripotent hap stem cells differentiate to beating cardiac muscle cells
    Cell Cycle, 2015
    Co-Authors: Masateru Yashiro, Robert M. Hoffman, Yuko Hamada, Katsumasa Kawahara, Nobuko Arakawa, Yasuyuki Amoh
    Abstract:

    We have previously demonstrated that the neural stem-cell marker nestin is expressed in hair follicle stem cells located in the bulge area which are termed hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells from mouse and human could form spheres in culture, termed hair spheres, which are keratin 15-negative and CD34-positive and could differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we demonstrated that nestin-expressing stem cells could effect nerve and Spinal Cord Regeneration in mouse models. In the present study, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. We separated the mouse vibrissa hair follicle into 3 parts (upper, middle, and lower), and suspended each part separately in DMEM containing 10% FBS. All three parts of hair follicle differentiated to beating cardiac muscle cells as well as neurons, glial cells, keratinocytes and smooth muscle cells. The differentiation potential to...