Syringic acid delivered via mPEG-PLGA-PLL nanoparticles enhances peripheral nerve regeneration effect

Aim: To deliver syringic acid (SA) with a nanocarrier and enhance its function. Materials & methods: mPEG-PLGA-PLL (PEAL) nanoparticles were used to deliver SA. The characterization, storage stability, drug release, blood-compatibility and biocompatibility of SA-PEAL were detected by in vitro and in vivo assays. Cellular phenotypic experiments and rat sciatic nerve injury models were used to evaluate the function of SA-PEALs. Results: SA-PEAL had good storage stability, blood-compatibility and biocompatibility and could slowly release SA. SA-PEAL significantly enhanced the proliferation and migration ability of Schwann cells and function recovery of injured sciatic nerves. Conclusion: Our study provides an effective nano-delivery system for enhancing the neural repair function of SA and promoting further applications of SA.

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In vitro, In vivo and Ex vivo Models for Peripheral Nerve Injury and Regeneration

Current Neuropharmacology ◽

10.2174/1570159x19666210407155543 ◽

2021 ◽

Vol 19 ◽

Author(s):

Andrew Li ◽

Clifford Pereira ◽

Elise Eleanor Hill ◽

Olivia Vukcevich ◽

Aijun Wang

Keyword(s):

Peripheral Nerve ◽

Peripheral Nerve Injury ◽

Ex Vivo ◽

Peripheral Nerve Regeneration ◽

Therapeutic Interventions ◽

Peripheral Nerve Injuries ◽

Traumatic Injuries ◽

And Function

: Peripheral nerve injuries (PNI) frequently occur secondary to traumatic injuries. Recovery from these injuries can be expectedly poor, especially in proximal injuries. In order to study and improve peripheral nerve regeneration, scientists rely on peripheral nerve models to identify and test therapeutic interventions. In this review, we discuss the best described and most commonly used peripheral nerve models that scientists have and continue to use to study peripheral nerve physiology and function.

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Ikaros is absolutely required for pre-B cell differentiation by attenuating IL-7 signals

Journal of Experimental Medicine ◽

10.1084/jem.20131735 ◽

2013 ◽

Vol 210 (13) ◽

pp. 2823-2832 ◽

Cited By ~ 57

Author(s):

Beate Heizmann ◽

Philippe Kastner ◽

Susan Chan

Keyword(s):

Cell Differentiation ◽

B Cells ◽

B Cell ◽

Cell Receptor ◽

B Cell Differentiation ◽

B Cell Signaling ◽

And Migration ◽

And Function

Pre-B cell receptor (pre-BCR) signaling and migration from IL-7–rich environments cooperate to drive pre-B cell differentiation via transcriptional programs that remain unclear. We show that the Ikaros transcription factor is required for the differentiation of large pre-B to small pre-B cells. Mice deleted for Ikaros in pro/pre-B cells show a complete block of differentiation at the fraction C′ stage, and Ikaros-null pre-B cells cannot differentiate upon withdrawal of IL-7 in vitro. Restoration of Ikaros function rescues pre-B cell differentiation in vitro and in vivo and depends on DNA binding. Ikaros is required for the down-regulation of the pre-BCR, Igκ germline transcription, and Ig L chain recombination. Furthermore, Ikaros antagonizes the IL-7–dependent regulation of >3,000 genes, many of which are up- or down-regulated between fractions C′ and D. Affected genes include those important for survival, metabolism, B cell signaling, and function, as well as transcriptional regulators like Ebf1, Pax5, and the Foxo1 family. Our data thus identify Ikaros as a central regulator of IL-7 signaling and pre-B cell development.

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Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability

The Journal of Cell Biology ◽

10.1083/jcb.200512085 ◽

2006 ◽

Vol 174 (2) ◽

pp. 231-243 ◽

Cited By ~ 151

Author(s):

Beatriz G. Galvez ◽

Maurilio Sampaolesi ◽

Silvia Brunelli ◽

Diego Covarello ◽

Manuela Gavina ◽

...

Keyword(s):

Cell Therapy ◽

Dystrophic Muscle ◽

Migration Ability ◽

Efficient Delivery ◽

Tnf Α ◽

Combined Pretreatment ◽

And Migration ◽

Necrosis Factor

Efficient delivery of cells to target tissues is a major problem in cell therapy. We report that enhancing delivery of mesoangioblasts leads to a complete reconstitution of downstream skeletal muscles in a mouse model of severe muscular dystrophy (α-sarcoglycan ko). Mesoangioblasts, vessel-associated stem cells, were exposed to several cytokines, among which stromal- derived factor (SDF) 1 or tumor necrosis factor (TNF) α were the most potent in enhancing transmigration in vitro and migration into dystrophic muscle in vivo. Transient expression of α4 integrins or L-selectin also increased several fold migration both in vitro and in vivo. Therefore, combined pretreatment with SDF-1 or TNF-α and expression of α4 integrin leads to massive colonization (>50%) followed by reconstitution of >80% of α-sarcoglycan–expressing fibers, with a fivefold increase in efficiency in comparison with control cells. This study defines the requirements for efficient engraftment of mesoangioblasts and offers a new potent tool to optimize future cell therapy protocols for muscular dystrophies.

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Opposing effects of bim and bcl-2 on lung endothelial cell migration

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00390.2009 ◽

2010 ◽

Vol 299 (5) ◽

pp. L607-L620 ◽

Cited By ~ 18

Author(s):

Cathy Grutzmacher ◽

SunYoung Park ◽

Tammy L. Elmergreen ◽

Yixin Tang ◽

Elizabeth A. Scheef ◽

...

Keyword(s):

Matrix Protein ◽

Endothelial Cell Migration ◽

Cellular Mechanisms ◽

Capillary Morphogenesis ◽

Steady State Rate ◽

Cell Adhesion And Migration ◽

And Migration ◽

And Function

Integration of cell adhesive, survival, and proliferative processes is essential for capillary morphogenesis of endothelial cells (EC) in vitro and vascular development and function in vivo. Unfortunately, the molecular and cellular mechanisms that impact these processes are poorly defined. Here we examined how lack of bim and/or bcl-2 expression impact lung EC function. The absence of bcl-2 or bim had a significant impact on EC adhesion and migration. Lack of bcl-2 expression decreased lung EC migration, whereas lack of bim expression increased migration compared with their wild-type counterparts. Decreased adhesion to fibronectin and vitronectin was observed in both bcl-2−/− and bim−/− lung EC, with bcl-2−/− EC having very little adhesion to either matrix protein. Capillary morphogenesis was greatly diminished in bcl-2−/− EC, which correlated with decreased lung alveolarization in vivo, an angiogenesis-dependent process. We also observed aberrant production of extracellular matrix proteins, eNOS expression, and nitric oxide production in bcl-2−/− lung EC, which could contribute to inability to undergo capillary morphogenesis. The changes in cell adhesion and migration noted in the absence of bim or bcl-2 were independent of their impact on apoptosis. We observed no significant affect on the steady-state rate of apoptosis of lung EC in the absence of bim or bcl-2. Thus, bcl-2 family members, bim and bcl-2, play a central role in modulation of EC proangiogenic properties, which goes beyond their role as simple mediators of mitochondrial homeostasis and apoptosis.

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Comparative Analysis of the Cell Fates of Induced Schwann Cells from Subcutaneous Fat Tissue and Naïve Schwann Cells in the Sciatic Nerve Injury Model

BioMed Research International ◽

10.1155/2017/1252851 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Mingzi Zhang ◽

Mei Hua Jiang ◽

Dae-Wook Kim ◽

Woosung Ahn ◽

Eunkyung Chung ◽

...

Keyword(s):

Sciatic Nerve ◽

Schwann Cells ◽

Subcutaneous Fat ◽

Basal Membrane ◽

Nerve Lesion ◽

And Migration ◽

Migration Capacity ◽

And Function

Purpose. The fate and function of the induced Schwann cells (iSCs) like cells from adipose tissue have not been critically evaluated in vivo after transplantation. The objective of this study is to compare the fate of iSCs with naïve SCs (nSCs) after transplantation into the lesion sites of sciatic nerve, respectively. Methods. Adipose-derived stem cells from eGFP-expressing transgenic rat’s subcutaneous fat were induced to iSCs in vitro. iSCs were injected to the sciatic nerve lesion area after crush injury and the cells fate was comparatively analyzed with that of nSCs from the same rat. Results. At 12 weeks after transplantation, nSCs were detected only in the restricted area of cell transplantation site but iSCs were widely distributed all over the sciatic nerve. Based on double fluorescence observations, both iSCs and naïve ones were colocalized with P0-expressing myelin sheath, outbound by laminin-expressing basal membrane, and terminated at contactin-associated protein-expressing doublets. However, some of iSCs were also differentiated to the fibrocyte/fibroblast-like cells. In the histological analysis of repaired sciatic nerves, axon density was higher in iSC-received group than in the nSCs group and normal sciatic nerve. Conclusion. iSCs induced from subcutaneous fat tissues have higher engraftment and migration capacity than nSCs.

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Ginsenoside M1 Induces Apoptosis and Inhibits the Migration of Human Oral Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21249704 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9704

Author(s):

Yu-Chieh Lee ◽

Wei-Ting Wong ◽

Lan-Hui Li ◽

Lichieh Julie Chu ◽

Mridula P. Menon ◽

...

Keyword(s):

Annexin V ◽

Panax Notoginseng ◽

Positive Staining ◽

Dna Breaks ◽

Double Positive ◽

Migration Ability ◽

Oral Cancer Cells ◽

And Migration

Oral squamous cell carcinoma (OSCC) accounts for 5.8% of all malignancies in Taiwan, and the incidence of OSCC is on the rise. OSCC is also a common malignancy worldwide, and the five-year survival rate remains poor. Therefore, new and effective treatments are needed to control OSCC. In the present study, we prepared ginsenoside M1 (20-O-beta-d-glucopyranosyl-20(S)-protopanaxadiol), a major deglycosylated metabolite of ginsenoside, through the biotransformation of Panax notoginseng leaves by the fungus SP-LSL-002. We investigated the anti-OSCC activity and associated mechanisms of ginsenoside M1 in vitro and in vivo. We demonstrated that ginsenoside M1 dose-dependently inhibited the viability of human OSCC SAS and OEC-M1 cells. To gain further insight into the mode of action of ginsenoside M1, we demonstrated that ginsenoside M1 increased the expression levels of Bak, Bad, and p53 and induced apoptotic DNA breaks, G1 phase arrest, PI/Annexin V double-positive staining, and caspase-3/9 activation. In addition, we demonstrated that ginsenoside M1 dose-dependently inhibited the colony formation and migration ability of SAS and OEC-M1 cells and reduced the expression of metastasis-related protein vimentin. Furthermore, oral administration or subcutaneous injection of ginsenoside M1 significantly reduced tumor growth in SAS xenograft mice. These results indicate that ginsenoside M1 can be translated into a potential therapeutic against OSCC.

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Isoflurane Preconditioning Promotes the Survival and Migration of Bone Marrow Stromal Cells

Cellular Physiology and Biochemistry ◽

10.1159/000430300 ◽

2015 ◽

Vol 36 (4) ◽

pp. 1331-1345 ◽

Cited By ~ 5

Author(s):

Yu Sun ◽

Qi-fang Li ◽

Jia Yan ◽

Rong Hu ◽

Hong Jiang

Keyword(s):

Bone Marrow ◽

Hypoxia Inducible Factor ◽

Volatile Anesthetic ◽

Protective Effects ◽

In Vivo Experiments ◽

High Doses ◽

And Migration ◽

And Function

Background: Preconditioning with the volatile anesthetic isoflurane exerts protective effects in animal models of ischemia. The cytoprotective effects of isoflurane are dependent on the expression of hypoxia inducible factor-1 (HIF-1), a dimeric transcription factor that mediates cellular responses to hypoxia. Methods: We investigated the effect of isoflurane preconditioning on bone marrow stromal cell (BMSC) survival and function. Results: Short exposures to low isoflurane concentrations promoted in vitro survival and migration of BMSCs, whereas long exposures and high doses had the opposite effect. At specific doses and times, isoflurane upregulated the expression of HIF-1α and the stromal-derived factor-1 receptor CXCR4, and induced the activation of Akt, similar to hypoxia, and the effect of isoflurane was abrogated by silencing of HIF-1α or inhibition of PI3K/Akt signaling. In vivo experiments showed that isoflurane preconditioning increased the engraftment of BMSCs into the ischemic brain and improved functional recovery in a mouse model of stroke. Conclusion: Isoflurane preconditioning at specific doses and times improves the survival and function of BMSCs through the upregulation of CXCR4 via a mechanism involving HIF-1α expression and the PI3K/Akt pathway, suggesting that anesthetic preconditioning could be developed as a strategy to improve the efficiency of cell therapy.

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Geranyl-geraniol addition affects potency of bisphosphonates—a comparison in vitro promising a therapeutic approach for bisphosphonate-associated osteonecrosis of the jaw and oral wound healing

Oral and Maxillofacial Surgery ◽

10.1007/s10006-021-00982-8 ◽

2021 ◽

Author(s):

Marius Otto ◽

Christine Lux ◽

Tilo Schlittenbauer ◽

Frank Halling ◽

Thomas Ziebart

Keyword(s):

Endothelial Cells ◽

Cell Viability ◽

Osteonecrosis Of The Jaw ◽

Dermal Fibroblasts ◽

Human Umbilical Cord ◽

Depressing Effect ◽

Migration Ability ◽

And Migration

Abstract Purpose Analysis of the influence of geranyl-geraniol (GG) addition on four bisphosphonate derivatives regarding their influence on cell viability and migration ability of bone metabolism and endothelial cells in vitro. Methods Clodronate, pamidronate, ibandronate, and zoledronate were observed with and without GG addition, for their effect on human osteoblasts (HOB), normal human dermal fibroblasts (NHDF), human endothelial progenitor cells (EPC), and endothelial cells of the human umbilical cord (HUVEC) using migration-, MTT-, and colony-forming cell assays. Results Data pointed to a depressing effect of all bisphosphonates on the migration ability of NHDF, EPC, and HOB. MTT assay demonstrated a decreased cell viability of HUVEC of all bisphosphonates in a 50 μM concentration and of NHDF when treated with 50 μM of clodronate, ibandronate, or zoledronate. Tested drugs showed a depressing effect on colony-forming potential of EPC even in a 5 μM concentration. GG addition demonstrated an attenuate impact on bisphosphonate effect on all primary cell cultures, respectively. Conclusion In vitro comparison showed that the addition of GG weakens the effect of all bisphosphonates examined. It supports investigations that suggest GG to be able to prevent bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) in vivo. Future clinical trials may discover the local therapeutic use of GG for the prevention of BP-ONJ.

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Fibronectin precoating wound bed enhances the therapeutic effects of autologous epidermal basal cell suspension for full-thickness wounds by improving epidermal stem cells’ utilization

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1236-7 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 6

Author(s):

Peng Wang ◽

Zhicheng Hu ◽

Xiaoling Cao ◽

Shaobin Huang ◽

Yunxian Dong ◽

...

Keyword(s):

Wound Healing ◽

In Vitro Study ◽

Epidermal Stem Cells ◽

Full Thickness ◽

Collagen Formation ◽

And Migration ◽

And Function ◽

Proliferation And Migration

Abstract Background Autologous epidermal basal cell suspension therapy has been proven to be one of the most effective treatments for full-thickness wounds. However, we found there remain obvious defects that significantly confined the utilization and function of the epidermal basal cells (EBCs), especially the epidermal stem cells (ESCs) in it. This study investigated whether precoating fibronectin (FN) on the wound bed before spraying EBCs could overcome these defects and further explored its possible mechanisms. Methods In the in vitro study, EBCs were isolated from the donor skin of patients who needed skin grafting. Different concentrations of FN were used to precoat culture dishes before cell culture; the adherent efficiency, proliferation and migration ability of ESCs were analyzed and compared with traditional collagen IV precoating. In the in vivo study, Sprague–Dawley (SD) rats with full-thickness skin wounds were selected as full-thickness wounds’ model. For the experiment groups, 20 μg/ml FN was precoated on the wound bed 10 min before EBC spray. The quality of wound healing was estimated by the residual wound area rate, wound healing time, and hematoxylin and eosin (H&E) staining. Expression of ESC markers, neovascular markers, inflammation markers, and collagen formation and degradation markers was elucidated by immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), and RT-qPCR analysis. Results The in vitro study showed that the dishes precoated with 20 μg/ml FN had a similar adherent efficiency and colony formation rate with collagen IV, but it could improve the proliferation and migration of ESCs significantly. Similarly, in the in vivo study, precoating FN on wound bed before EBC spray also significantly promote wound healing by improving ESCs’ utilization efficiency, promoting angiogenesis, decreasing inflammations, and regulating collagen formation and degradation. Conclusion FN precoating wound bed before EBC spray could significantly promote full-thickness wound healing by improving the utilization and function of the ESCs and further by promoting angiogenesis, decreasing inflammations, and regulating collagen formation and degradation. Graphical abstract

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Localisation of the hyaluronan receptor CD44 in porcine cumulus cells during in vivo and in vitro maturation

Zygote ◽

10.1017/s0967199402004057 ◽

2002 ◽

Vol 10 (4) ◽

pp. 317-326 ◽

Cited By ~ 17

Author(s):

Masaki Yokoo ◽

Paisan Tienthai ◽

Naoko Kimura ◽

Koji Niwa ◽

Eimei Sato ◽

...

Keyword(s):

Oocyte Maturation ◽

In Vitro Maturation ◽

Cumulus Cells ◽

Culture Conditions ◽

Binding Ability ◽

Migration Ability ◽

And Migration ◽

Boar Spermatozoa

Polyspermy is fairly common during porcine in vitro fertilisation (IVF), perhaps due to incomplete in vitro oocyte maturation (IVM). Porcine cumulus cells (CCs) layered around the oocyte produce large amounts of extracellular hyaluronan (HA) when forming an expanding cell cloud during the last phase of oocyte maturation. The specific actions of HA are mediated via HA-binding proteins (HABPs), such as CD44, which act as receptors. In this study using immunocytochemistry and western blotting we investigated the localisation of CD44 in CCs obtained from in vivo-matured pig cumulus-oocyte complexes (COCs) and compared it with that in CCs from immature COCs and of COCs subjected to IVM and IVF procedures. Immunolabelling of CD44 was absent or very weak in CCs from immature COCs but strongly present on the surface of the CCs obtained from in vivo, displaying a similar localisation in the in vitro-matured COCs. In the latter, the labelling decreased but did not disappear in CCs 4 h after sperm co-incubation during IVF. Immunoblotting detected bands of between 73 and 88 kDa, corresponding to CD44, in the protein extract from in vivo CCs collected immediately prior to, or following spontaneous ovulation. The in vitro-matured CCs, however, presented bands ranging from 81 kDa to 88 kDa. Also, the bands found in the in vivo-matured CCs showed a larger variation of intensity and migration among animals than did the batches of in vitro-matured CCs. No CD44 band was detected on aliquots of the frozen-thawed boar spermatozoa used for IVF. The results clearly demonstrate that the specific HA receptor CD44 is present in expanding CCs of in vivo-matured pig COCs, in relation to increasing amounts of inter-CC HA. The subtle differences in molecular weight and migration ability observed between in vivo and in vitro samples may relate to differences in glycosylation and thus explain differences in HA-binding ability, of consequence for optimising in vitro culture conditions.

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