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1.
Biomaterials ; 209: 1-9, 2019 07.
Article in English | MEDLINE | ID: mdl-31022556

ABSTRACT

Segmental injuries to peripheral nerves (PNs) too often result in lifelong disability or pain syndromes due to a lack of restorative treatment options. For injuries beyond a critical size, a bridging device must be inserted to direct regeneration. PN allografts from immunologically incompatible donors are highly effective bridging devices but are not a regular clinical option because of the expense and health risks of systemic immunosuppression (ISN). We have developed a method to deliver a single administration of ISN localized around a PN allograft that circumvents the risks of systemic ISN. Localized ISN was provided by regulatory T cells (Tregs), a potently immunosuppressive cell type, that was delivered around a PN allograft with a poly(ethylene glycol) norbornene (PEGNB) degradable hydrogel. Tregs are released from the hydrogel over 14 d, infiltrate the graft, suppress the host immune response and facilitate regeneration of the recipient rats equal to the autograft control. Furthermore, this method was effective in a segmental PN defect that included a branch point, for which there currently exist no treatment options. These results show that localized delivery of immunosuppressive cells for PN allografts is an effective new strategy for treating segmental PN defects that can also be used to regenerate complex nerve structures.


Subject(s)
Hydrogels/chemistry , Peripheral Nerves/cytology , Peripheral Nerves/physiology , T-Lymphocytes, Regulatory/metabolism , Animals , Nerve Regeneration/physiology , Rats , Rats, Sprague-Dawley , Transplantation, Homologous
2.
Methods Mol Biol ; 1797: 165-175, 2018.
Article in English | MEDLINE | ID: mdl-29896691

ABSTRACT

Embryonic stem cells (ESC) are widely used due to their unlimited capacity of differentiation into different cell lineages, which makes ESC a viable choice as a toxicology test model. Toxicological analysis using embryonic stem cells (ESC) has become an important tool in toxicology procedures. Regarding toxicological analysis methods, flow cytometry (FC) is one technique designed to detect and evaluate cells in suspension, for example, ESC suspension, thus making possible to study different biological, physical, and/or chemical characteristics of cells. Thus, FC can be very useful for cell toxicology and tumorigenic analyses.


Subject(s)
Cell Differentiation , Flow Cytometry/methods , Mouse Embryonic Stem Cells/pathology , Teratogens/toxicity , Toxicity Tests/methods , Toxicology/methods , Animals , Cell Lineage , Mice , Mouse Embryonic Stem Cells/drug effects
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