Stem cells in nerve reconstruction: Hype, hope or reality?

The overarching goal of this thesis is to further improve outcomes after nerve reconstruction by individualizing nerve allograft repair with the addition of adipose-derived MSCs. The aim of the first part was to investigate the clinical problem. In chapter 2, an evidencebased overview of the effectiveness of nerve conduits and allografts in motor and mixed sensory/motor nerve reconstruction is provided. In chapter 3, the outcomes of digital nerve gap reconstruction with the NeuraGen type 1 collagen nerve conduit and the Avance Nerve Graft are reported in a retrospective observational study. The second part of this thesis focuses on the addition of adipose derived MSCs to decellularized nerve allografts and the in-vitro characteristics on human tissue, as well as the in-vivo characteristics in a rat-model. An adequate, reliable and validated cell seeding technique is an essential step for evaluating the translational utility of MSC-enhanced decellularized nerve grafts. Therefore in chapter 4, a new method to effectively seed decellularized nerve allografts with MSCs is described and validated. To understand how the functions of MSCs can be leveraged for peripheral nerve repair, in chapter 5, we investigated whether interactions of MSCs with decellularized nerve allografts can improve mRNA and protein expression of growth factors that may support nerve regeneration. After in-vitro testing, the MSC seeded nerve allograft was implemented in a rat model. As there is a paucity of information regarding the ultimate survivorship of implanted MSCs or if these cells remain where they are placed, in chapter 6, the in-vivo distribution and survival of MSCs seeded on a decellularized nerve allograft was tracked using luciferase based bioluminescent imaging (BLI). In chapter 7, the molecular mechanisms underlying nerve repair by a decelullarized nerve allograft preseeded with autologous, undifferentiated, adipose derived MSCs are studied and compared to the unseeded allograft and autograft nerve. In the general discussion (chapter 8) the results of this thesis are put into a broader perspective and compared to other recent publications. Furthermore, the implications of this research for future perspectives are discussed

Gene expression and growth factor analysis in early nerve regeneration following segmental nerve defect reconstruction with a mesenchymal stromal cell-enhanced decellularized nerve allograft

Abstract Background: The purpose of this study was to evaluate the molecular mechanisms underlying nerve repair by a decellularized nerve allograft seeded with adipose-derived mesenchymal stromal cells (MSCs) and compare it to the unseeded allograft and autograft nerve. Methods: Undifferentiated MSCs were seeded onto decellularized nerve allografts and used to reconstruct a 10 mm gap in a rat sciatic nerve model. Gene expression profiles of genes essential for nerve regeneration and immunohistochemical staining (IHC) for PGP9.5, NGF, RECA-1, and S100 were obtained 2 weeks postoperatively. Results: Semi-quantitative RT-PCR analysis showed that the angiogenic molecule VEGFA was significantly increased in seeded allografts, and transcription factor SOX2 was downregulated in seeded allografts. Seeded grafts showed a significant increase in immunohistochemical markers NGF and RECA-1, when compared with unseeded allografts. Conclusions: MSCs contributed to the secretion of trophic factors. A beneficial effect of the MSCs on angiogenesis was found when compared with the unseeded nerve allograft, but implanted MSCs did not show evidence of differentiation into Schwann cell-like cells

Gene expression and growth factor analysis in early nerve regeneration following segmental nerve defect reconstruction with a mesenchymal stromal cell-enhanced decellularized nerve all

Background: The purpose of this study was to evaluate the molecular mechanisms underlying nerve repair by a decellularized nerve allograft seeded with adiposederived mesenchymal stromal cells (MSCs) and compare it to the unseeded allograft and autograft nerve. Methods: Undifferentiated MSCs were seeded onto decellularized nerve allografts and used to reconstruct a 10 mm gap in a rat sciatic nerve model. Gene expression profiles of genes essential for nerve regeneration and immunohistochemical staining (IHC) for PGP9.5, NGF, RECA-1, and S100 were obtained 2 weeks postoperatively. Results: Semi-quantitative RT-PCR analysis showed that the angiogenic molecule VEGFA was significantly increased in seeded allografts, and transcription factor SOX2 was downregulated in seeded allografts. Seeded grafts showed a significant increase in immunohistochemical markers NGF and RECA-1, when compared with unseeded allografts. Conclusions: MSCs contributed to the secretion of trophic factors. A beneficial effect of the MSCs on angiogenesis was found when compared with the unseeded nerve allograft, but implanted MSCs did not show evidence of differentiation into Schwann cell-like cells

A basic fibroblast growth factor slow‐release system combined to a biodegradable nerve conduit improves endothelial cell and Schwann cell proliferation: A preliminary study in a rat model

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146569/1/micr30387.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146569/2/micr30387_am.pd

التوجيه النحوي للوقف الهبطي في القرآن الكريم وأ ثره في المعنى

موضوع البحث يختص بالتوجيه النحوي للوقف الهبطي_المعتمد في مصاحف المغاربة_ وللإمام الهبطي منهج خاص في وضع الوقف، سعى من خلاله إلى تقصير الجمل وتكثير الوقوف؛ استجابة لخاصية القراءة جماعة التي اعتاد الناس عليها في محيطه. وقد أثبتت الدراسة تجلي الأثر النحوي في الأوقاف الهبطية، كما بينت موافقة الأوقاف الهبطية لمواضع وقوف المشارقة غالبا. ومن ثم أثبتت أن الإمام الهبطي سليم البصيرة النحوية وعالم بأسس وضع الوقف،كما أنه اعتمد في تخير معظم أوقافه على من تقدم. هذا ومن أوقافه ما لا يدرك كنهه في النظرة العجلى؛ لاعتماده التقدير وخفي الإعراب، وبالتأمل نجد التخريج المسوغ لذلك. وقليل من أوقافه ما هو غريب، إلا أنه يجب الأخذ بعين الاعتبار أخطاء النساخ التي لا يمكن بأية حال أن تحسب على الشيخ الهبط

Spatial econometrics : methods and applications

vi+281hlm.;23c