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Michael G Fehlings - One of the best experts on this subject based on the ideXlab platform.

  • an in vivo characterization of trophic factor production following neural precursor cell or bone marrow stromal cell Transplantation for spinal cord injury
    Stem Cells and Development, 2012
    Co-Authors: Gregory W. J. Hawryluk, Shelly Wang, Andrea J. Mothe, Charles H. Tator, Michael G Fehlings
    Abstract:

    Cellular Transplantation strategies for repairing the injured spinal cord have shown consistent benefit in preclinical models, and human clinical trials have begun. Interactions between transplanted cells and host tissue remain poorly understood. Trophic factor secretion is postulated a primary or supplementary mechanism of action for many transplanted cells, however, there is little direct evidence to support trophin production by transplanted cells in situ. In the present study, trophic factor expression was characterized in uninjured, injured-untreated, injured-treated with transplanted cells, and corresponding control tissue from the adult rat spinal cord. Candidate trophic factors were identified in a literature search, and primers were designed for these genes. We examined in vivo trophin expression in 3 paradigms involving Transplantation of either brain or spinal cord-derived neural precursor cells (NPCs) or bone marrow stromal cells (BMSCs). Injury without further treatment led to a significant e...

  • in vitro characterization of trophic factor expression in neural precursor cells
    Stem Cells and Development, 2012
    Co-Authors: Gregory W. J. Hawryluk, Mahmood Chamankhah, Andrea J. Mothe, Charles H. Tator, Michael G Fehlings
    Abstract:

    In Cellular Transplantation strategies for repairing the injured central nervous system, interactions between transplanted neural precursor cells (NPCs) and host tissue remain incompletely understood. Although trophins may contribute to the benefits observed, little research has explored this possibility. Candidate trophic factors were identified, and primers were designed for these genes. Template RNA was isolated from 3 NPC sources, and also from bone marrow stromal cells (BMSCs) and embryonic fibroblasts as comparative controls. Quantitative polymerase chain reaction was performed to determine the effect of cell source, passaging, Cellular differentiation, and environmental changes on trophin factor expression in NPCs. Results were analyzed with multivariate statistical analyses. NPCs, BMSCs, and fibroblasts each expressed trophic factors in unique patterns. Trophic factor expression was similar among NPCs whether harvested from rat or mouse, brain or spinal cord, or their time in culture. The expressi...

Gregory W. J. Hawryluk - One of the best experts on this subject based on the ideXlab platform.

  • an in vivo characterization of trophic factor production following neural precursor cell or bone marrow stromal cell Transplantation for spinal cord injury
    Stem Cells and Development, 2012
    Co-Authors: Gregory W. J. Hawryluk, Shelly Wang, Andrea J. Mothe, Charles H. Tator, Michael G Fehlings
    Abstract:

    Cellular Transplantation strategies for repairing the injured spinal cord have shown consistent benefit in preclinical models, and human clinical trials have begun. Interactions between transplanted cells and host tissue remain poorly understood. Trophic factor secretion is postulated a primary or supplementary mechanism of action for many transplanted cells, however, there is little direct evidence to support trophin production by transplanted cells in situ. In the present study, trophic factor expression was characterized in uninjured, injured-untreated, injured-treated with transplanted cells, and corresponding control tissue from the adult rat spinal cord. Candidate trophic factors were identified in a literature search, and primers were designed for these genes. We examined in vivo trophin expression in 3 paradigms involving Transplantation of either brain or spinal cord-derived neural precursor cells (NPCs) or bone marrow stromal cells (BMSCs). Injury without further treatment led to a significant e...

  • in vitro characterization of trophic factor expression in neural precursor cells
    Stem Cells and Development, 2012
    Co-Authors: Gregory W. J. Hawryluk, Mahmood Chamankhah, Andrea J. Mothe, Charles H. Tator, Michael G Fehlings
    Abstract:

    In Cellular Transplantation strategies for repairing the injured central nervous system, interactions between transplanted neural precursor cells (NPCs) and host tissue remain incompletely understood. Although trophins may contribute to the benefits observed, little research has explored this possibility. Candidate trophic factors were identified, and primers were designed for these genes. Template RNA was isolated from 3 NPC sources, and also from bone marrow stromal cells (BMSCs) and embryonic fibroblasts as comparative controls. Quantitative polymerase chain reaction was performed to determine the effect of cell source, passaging, Cellular differentiation, and environmental changes on trophin factor expression in NPCs. Results were analyzed with multivariate statistical analyses. NPCs, BMSCs, and fibroblasts each expressed trophic factors in unique patterns. Trophic factor expression was similar among NPCs whether harvested from rat or mouse, brain or spinal cord, or their time in culture. The expressi...

Antonio J Salgado - One of the best experts on this subject based on the ideXlab platform.

  • combination of a peptide modified gellan gum hydrogel with cell therapy in a lumbar spinal cord injury animal model
    Biomaterials, 2016
    Co-Authors: Eduardo D Gomes, Molly S Shoichet, Sofia Silva Mendes, Hugo Leitealmeida, Jeffrey M Gimble, Roger Y Tam, Nuno Sousa, Nuno A Silva, Antonio J Salgado
    Abstract:

    Spinal Cord Injury (SCI) is a highly incapacitating condition for which there is still no cure. Current clinical approaches are mainly based on palliative care, so there is a need to find possible treatments to SCI. Cellular Transplantation is regarded with great expectation due to the therapeutic potential of cells such as Adipose tissue-derived Stromal/Stem Cells (ASCs) or Olfactory Ensheathing Cells (OECs). Both are accessible sources and present positive paracrine and cell-to-cell interactions, previously reported by our group. Additionally, biomaterials such as hydrogels have been applied in SCI repair with promising results. We propose to combine a GRGDS-modified gellan gum hydrogel with ASCs and OECs in order to promote SCI regeneration. In vitro, ASCs and OECs could be co-cultured within GG-GRGDS hydrogels inducing a more robust neurite outgrowth when compared to controls. In vivo experiments in a hemisection SCI rat model revealed that the administration of ASCs and OECs encapsulated in a GG-GRGDS hydrogel led to significant motor improvements when compared to both control (SCI) and hydrogel alone (GG-GRGDS) groups. This was accompanied by a decreased infiltration of inflammatory cells and astrocytes, and by an increased intensity of neurofilament. These results suggest evident gains induced by the encapsulation of ASCs and OECs in GG-GRGDS based hydrogels.

A James M Shapiro - One of the best experts on this subject based on the ideXlab platform.

  • progress in translational regulatory t cell therapies for type 1 diabetes and islet Transplantation
    Endocrine Reviews, 2020
    Co-Authors: Braulio A Marfilgarza, Rena Pawlick, Joshua Hefler, Mario Bermudez De Leon, Nidheesh Dadheech, A James M Shapiro
    Abstract:

    Regulatory T cells (Tregs) have become highly relevant in the pathophysiology and treatment of autoimmune diseases, such as type 1 diabetes (T1D). As these cells are known to be defective in T1D, recent efforts have explored ex vivo and in vivo Treg expansion and enhancement as a means for restoring self-tolerance in this disease. Given their capacity to also modulate alloimmune responses, studies using Treg-based therapies have recently been undertaken in Transplantation. Islet Transplantation provides a unique opportunity to study the critical immunological crossroads between auto and alloimmunity. This procedure has advanced greatly in recent years, and reports of complete abrogation of severe hypoglycemia and long-term insulin independence have become increasingly reported. It is clear that Cellular Transplantation has the potential to be a true cure in T1D, provided the remaining barriers of cell supply and abrogated need for immune suppression can be overcome. However, the role that Tregs play in islet Transplantation remains to be defined. Herein, we synthesize the progress and current state of Treg-based therapies in T1D and islet Transplantation. We provide an extensive, but concise, background to understand the physiology and function of these cells and discuss the clinical evidence supporting potency and potential Treg-based therapies in the context of T1D and islet Transplantation. Finally, we discuss some areas of opportunity and potential research avenues to guide effective future clinical application. This review provides a basic framework of knowledge for clinicians and researchers involved in the care of patients with T1D and islet Transplantation.

  • a prevascularized subcutaneous device less site for islet and Cellular Transplantation
    Nature Biotechnology, 2015
    Co-Authors: Andrew R Pepper, Boris Galalopez, Rena Pawlick, Shaheed Merani, Tatsuya Kin, A James M Shapiro
    Abstract:

    Transplantation of donor-derived islets into the liver is a successful Cellular replacement therapy for individuals with diabetes. However, the hepatic vasculature is not an optimal transplant site for several reasons, including graft attrition and the inability to retrieve or image the islets. Here we describe islet Transplantation into a prevascularized, subcutaneous site created by temporary placement of a medically approved vascular access catheter. In mice with streptozotocin (STZ)-induced diabetes, Transplantation of ∼500 syngeneic islets into the resulting 'device-less' space reversed diabetes in 91% of mice and maintained normoglycemia for >100 days. The approach was also effective in mice with pre-existing diabetes, in another mouse strain that mounts a more vigorous inflammatory response, and across an allogeneic barrier. These results demonstrate that transient priming of a subcutaneous site supports diabetes-reversing islet Transplantation in mouse models without the need for a permanent cell-encapsulation device.

Joost Schouten - One of the best experts on this subject based on the ideXlab platform.

  • a review and rationale for the use of Cellular Transplantation as a therapeutic strategy for traumatic brain injury
    Journal of Neurotrauma, 2004
    Co-Authors: Joost Schouten, Carl T Fulp, Nicolas C Royo, Kathryn E Saatman, Deborah Watson, Evan Y Snyder, John Q Trojanowski, Darwin J Prockop
    Abstract:

    Experimental research during the past decade has greatly increased our understanding of the pathophysiology of traumatic brain injury (TBI) and allowed us to develop neuroprotective pharmacological therapies. Encouraging results of experimental pharmacological interventions, however, have not been translated into successful clinical trials, to date. Traumatic brain injury is now believed to be a progressive degenerative disease characterized by cell loss. The limited capacity for self-repair of the brain suggests that functional recovery following TBI is likely to require Cellular Transplantation of exogenous cells to replace those lost to trauma. Recent advances in central nervous system Transplantation techniques involve technical and experimental refinements and the analysis of the feasibility and efficacy of Transplantation of a range of stem cells, progenitor cells and postmitotic cells. Cellular Transplantation has begun to be evaluated in several models of experimental TBI, with promising results. The following is a compendium of these new and exciting studies, including a critical discussion of the rationale and caveats associated with Cellular Transplantation techniques in experimental TBI research. Further refinements in future research are likely to improve results from Transplantation-based treatments for TBI.