Kirsten Haastert-Talini

Hannover Medical School | MHH · Institute of Neuroanatomy and Cell Biology

Gut microbiota is responsible for essential functions in human health. Several communication axes between gut microbiota and other organs via neural, endocrine, and immune pathways have been described, and perturbation of gut microbiota composition has been implicated in the onset and progression of an emerging number of diseases. Here, we analyzed...

It has been widely demonstrated that the gut microbiota is responsible for essential functions in human health and that its perturbation is implicated in the development and progression of a growing list of diseases. The number of studies evaluating how the gut microbiota interacts with and influences other organs and systems in the body and vice v...

Adult human Schwann cells represent a relevant tool for studying peripheral neuropathies and developing regenerative therapies to treat nerve damage. Primary adult human Schwann cells are, however, difficult to obtain and challenging to propagate in culture. One potential solution is to generate Schwann cells from human induced pluripotent stem cel...

Background: The rabbit sciatic nerve injury model may represent a valuable alternative for critical gap distance seen in humans, but often leads to automutilation. In this study, we modified the complete sciatic nerve injury model for avoiding autophagy. Materials and Methods: In 20 adult female New Zealand White rabbits, instead of transecting th...

Peripheral nerves are frequently affected by lesions caused by trauma (work accidents, car incidents, combat injuries) and following surgical procedures (for instance cancer resection), resulting in loss of motor and sensory function with lifelong impairments. Irrespective of the intrinsic capability of the peripheral nervous system for regeneratio...

Polyvinylidene fluoride (PVDF) and its copolymer with trifluoroethylene (P(VDF-TrFE)) are considered as promising biomaterials for supporting nerve regeneration because of their proven biocompatibility and piezoelectric properties that could stimulate cell ingrowth due to their electrical activity upon mechanical deformation. For the first time, th...

Peripheral nerves are highly susceptible to injuries induced from everyday activities such as falling or work and sport accidents as well as more severe incidents such as car and motorcycle accidents. Many efforts have been made to improve nerve regeneration, but a satisfactory outcome is still unachieved, highlighting the need for easy to apply su...

Hollow nerve guidance conduits are approved for clinical use for defect lengths of up to 3 cm. This is because also in pre-clinical evaluation they are less effective in the support of nerve re-generation over critical defect lengths. Hydrogel luminal fillers are thought to improve the re-generation outcome by providing an optimized matrix inside t...

The International Association for the Study of Pain defines neuropathic pain as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system” (Treede et al., 2008). The associated changes can be observed in the peripheral as well as the central nervous system. The available literature discusses a wide variety of c...

Background In this viewpoint representatives of the Teaching Commission of the Anatomical Society summarize their teaching experiences gained during the COVID-19 pandemic in the summer term of 2020 and derive first recommendations concerning face-to-face and remote teaching of anatomy for the future. Methods Representatives of the Teaching Commiss...

Schwann cells play a crucial role in successful peripheral nerve repair and regeneration by supporting both axonal growth and myelination. Schwann cells are therefore a feasible option for cell therapy treatment of peripheral nerve injury. However, sourcing human Schwann cells at quantities required for development beyond research is challenging. D...

Surgical treatment of peripheral nerve injuries is still a major challenge in human clinic. Up to now, none of the well-developed microsurgical treatment options is able to guarantee a complete restoration of nerve function. This restriction is also effective for novel clinically approved artificial nerve guides. In this review, we compare surgical...

Background: Limb loss has a drastic impact on a patient's life. Severe trauma to the extremities is common in current military conflicts. Among other aspects, "life before limb" damage control surgery hinders immediate replantation within the short post-traumatic timeframe, which is limited in part by the ischemic time for successful replantation....

The rabbit has been proposed to represent an animal model that allows studying peripheral nerve regeneration across extended gap lengths. We describe here our experiences with the rabbit median nerve model and the obstacles it comes along with. This short communication is meant to inform the community and to prevent other researcher from investing...

In the current study we investigated the suitability of a novel hyaluronic acid–laminin hydrogel (HAL) as luminal filler and carrier system for co-transplanted cells within a composite chitosan-based nerve graft (CNG) in a rat critical nerve defect model. The HAL was meant to improve the performance of our artificial nerve guides by giving addition...

The successful introduction of innovative treatment strategies into clinical practise strongly depends on the availability of effective experimental models and their reliable pre-clinical assessment. Considering pre-clinical research for peripheral nerve repair and reconstruction, the far most used nerve regeneration model in the last decades is th...

Objectives To evaluate: (i) the neuro‐regenerative potential of chitosan membrane (CS‐Me) on acutely axotomised autonomic neurones in vitro; (ii) to exclude the possibility that a pro‐regenerative biomaterial could interfere with the proliferation activity of prostate cancer cell lines; (iii) to provide an in vivo proof of the biocompatibility and...

Tension-free surgical reconstruction of transected digital nerves in humans is regularly performed using autologous nerve grafts (ANGs) or bioartificial nerve grafts. Nerve grafts with increased bendability are needed to protect regenerating nerves in highly mobile extremity parts. We have recently demonstrated increased bendability and regeneratio...

A rabbit model for peripheral nerve regeneration at gap lengths approaching 3cm that limits autophagy,

Injuries to the peripheral nerves result in loss of motor, sensory and autonomic functions in the denervated segments of the body, thus having strong impact in the quality of life of affected patients. Neurons are able to regenerate their injured axons in the peripheral nerves; however, the endogenous repair mechanisms usually do not allow for a sa...

Severe peripheral nerve injuries are reconstructed either with autologous nerve grafts (gold standard) or alternatively with clinically approved artificial nerve guides. The most common method used to sterilize these medical products is ethylene oxide gassing (EO). However, this method has several disadvantages. An alternative, which has been barel...

Peripheral nerve injuries (PNI) resulting in a gap to be bridged between the transected nerve ends are commonly reconstructed with autologous nerve tissue, but there is a need for valuable alternatives. This experimental work considers the innovative use of the biomaterial Gellan Gum (GG) as luminal filler for nerve guidance channels made from chit...

Introduction The rat median nerve injury and repair model gets increasingly important for research on novel bioartificial nerve grafts. It allows follow‐up evaluation of the recovery of the forepaw functional ability with several sensitive techniques. The reflex‐based grasping test, the skilled forelimb reaching staircase test, as well as electrodi...

Reconstruction of joint‐crossing digital nerves requires the application of nerve guides with a much higher flexibility than used for peripheral nerve repair along larger bones. Nevertheless, collapse‐resistance should be preserved to avoid secondary damage to the regrowing nerve tissue. In recent years, we presented chitosan nerve guides (CNGs) to...

Background Delayed reconstruction of transection or laceration injuries of peripheral nerves is inflicted by a reduced regeneration capacity. Diabetic conditions, more frequently encountered in clinical practice, are known to further impair regeneration in peripheral nerves. Chitosan nerve guides (CNGs) have recently been introduced as a new genera...

The following paragraphs present a compressed overview of the latest developments in peripheral nerve tissue engineering and the main concepts underlying innovative approaches. Since several excellent review articles have been published recently and especially the biomaterial field is frequently bringing up novel developments, the reader with a dee...

This book focuses on posttraumatic repair and reconstruction of peripheral nerves. Written by internationally respected specialists, it provides an overview of the challenges and the latest advances in diagnosis and treatment of traumatic peripheral nerve injuries. It presents an outline of state-of the-art procedures from diagnostics, including ne...

Peripheral nerve injuries (PNI) are a world-spread problematic that affects over one million people. For PNI that require surgical intervention and in the case of long gap injuries, autologous nerve grafts (ANG) have been considered the gold standard for decades. However, the use of ANG is accompanying by several drawbacks, for instance, donor site...

Metal-organic frameworks (MOFs) are a promising platform for the synthesis of porous nanoparticles for diverse medical applications. Stefan Wuttke, Silke Meiners, and co-workers comprehensively investigate the nanosafety and hence the general applicability of different MOF nanoparticles for distinct fields of medical applications (e.g. drug deliver...

Progress in material development has enabled the production of nerve guides that increasingly resemble the characteristics of an autologous nerve graft. In the present study, 20 mm adult rat sciatic nerve defects were bridged with the collagen-based, two-component nerve guide 'Neuromaix', the commercially available NeuraGen® nerve tube or an autolo...

Metal-organic frameworks (MOFs) are promising platforms for the synthesis of nanoparticles for diverse medical applications. Their fundamental design principles allow for significant control of the framework architecture and pore chemistry, enabling directed functionalization for nanomedical applications. However, before applying novel nanomaterial...

Objective: (1) To introduce some key molecular players for the orchestration of repair processes of peripheral and cranial nerves. (2) To relate own experimental experiences in peripheral nerve repair to the conditions after cranial nerve injury and repair. (3) To give an outlook on current novelties in peripheral nerve reconstruction and their pot...

Critical length nerve defects in the rat sciatic nerve model were reconstructed with chitosan nerve guides filled with Schwann cell (SC) containing hydrogel. The transplanted SCs were naïve or have been genetically modified to over-express neurotrophic factors thus providing cellular neurotrophic factor delivery systems. Prior to the assessment in...

Biosynthetic nerve grafts are developed in order to complement or replace autologous nerve grafts for peripheral nerve reconstruction. Artificial nerve guides currently approved for clinical use are not widely applied in reconstructive surgery as they still have limitations especially when it comes to critical distance repair. Here we report a comp...

Previous studies revealed a peripheral nerve regeneration (PNR)1 promoting activity of Clostridium botulinum C32 exoenzyme or a 26mer C-terminal peptide fragment covering amino acids 156-181 (C3156-181),3 when delivered as one-time injection at the lesion site. The current study was performed to 1) investigate if prolonged availability of C3 and C3...

The study of peripheral nerve repair and regeneration is particularly relevant in the light of the high clinical incidence of nerve lesions. Yet, clinical outcome after nerve lesions is often far from being satisfactory and the functional recovery is almost never complete. Therefore, a number of therapeutic approaches are being investigated, rangin...

The peripheral nervous system has an intrinsic capability to regenerate, crucially related to the ability of Schwann cells (SC) to create a permissive environment, e.g. through production of regeneration promoting neurotrophic factors. Survival, proliferation, migration and differentiation of SC into a myelinating phenotype during development and a...

The development of realistic neuroanatomical models of peripheral nerves for simulation purposes requires the reconstruction of the morphology of the myelinated fibres in the nerve, including their nodes of Ranvier. Currently, this information has to be extracted by semimanual procedures, which severely limit the scalability of the experiments. In...

Purpose Innovative nerve conduits for peripheral nerve reconstruction are needed in order to specifically support peripheral nerve regeneration (PNR) whenever nerve autotransplantation is not an option. Specific support of PNR could be achieved by neurotrophic factor delivery within the nerve conduits via nanotechnology or stem cell engineering and...

Combined administration of the three np-NTFs fails to increase the number of neurites extending from adult DRG explants. Notes: (A) Bar graph representing the number of neuritic extensions of adult DRG explants (at distance 0 μm) treated with np-NGF (50 ng/mL) or with an np-NTF pool (np-NGF + np-FGF-218kDa + np-GDNF) in the concentration of 30 ng/m...

Nontransfected and EGFP-Flag-BMSCs in culture. Notes: (A) nT-BMSCs stained for F-actin filaments (red), demonstrating their regular fibroblast-like shape. (B) Anti-Flag (red) stained BMSCs after nonviral transfection with EGFP-Flag. Nuclear staining with 4′,6-diamidino-2-phenylindole (blue). Abbreviations: EGFP, enhanced green fluorescent protein;...

Neurotrophic factors conjugated to iron oxide nanoparticles stimulate neurite outgrowth from adult DRG explants in a dose-dependent manner. Notes: (A) Bar graph representing the number of neuritic extensions from adult DRG explants (at distance 0 μm) treated with different amounts of np-NTFs. Statistical analysis revealed the strongest effect on ne...

No synergistic effect is induced by supplementing NVR-Gel with a pool of np-NTFs. Notes: (A) Bar graphs depicting the number of neurite intersections (y-axis) with circles drawn at distinct distances (x-axis) from the neonatal DRG drop culture under control conditions or treatment with 50 ng/mL np-NGF or the 50 ng/mL np-NTF pool. No statistically s...

Local delivery of neurotrophic factors is a pillar of neural repair strategies in the peripheral nervous system. The main disadvantage of the free growth factors is their short half-life of few minutes. In order to prolong their activity, we have conjugated to iron oxide nanoparticles three neurotrophic factors: nerve growth factor (NGF), glial cel...

A variety of new bioartificial nerve guides have been tested preclinically for their safety and nerve regeneration supporting properties. So far, only a limited number of biomaterials have been tested in humans since the step from preclinical work to a clinical application is challenging. We here present an in vitro model with human Schwann cells (...

Die Rekonstruktion durchtrennter peripherer Nerven stellt immer dann eine besondere Herausforderung dar, wenn eine spannungsfreie Koaptation der Nervenstümpfe nicht möglich ist. Nervendefekte von wenigen Millimetern Länge können in der Regel in End-zu-End-Nahttechnik koaptiert werden. Bei Nervendefekten mit überkritischer Länge führt die direkte Ne...

We report on the performance of composite nerve grafts with an inner 3D multichannel porous chitosan core and an outer electrospun polycaprolactone shell. The inner chitosan core provided multiple guidance channels for regrowing axons. To analyze the in vivo properties of the bare chitosan cores, we separately implanted them into an epineural sheat...

Natural biomaterials have attracted an increasing interest in the field of tissue engineered nerve grafts, representing a possible alternative to autologous nerve transplantation. With the prospect of developing a novel entubulation strategy for transected nerves with cell-seeded chitosan films, we examined the biocompatibility of such films in vit...

Peripheral nerve injuries are the most frequent neurologic disorder in cattle. So far, no physiologic values have been established for the motor nerve conduction velocity (mNCV) in this precocial species. The electrophysiologic and morphometric reference values of peripheral nerves in calves were determined. It was hypothesized that these parameter...

The peripheral nervous system has the intrinsic capacity to regenerate axons into target tissues, and peripheral nerves severely damaged or transected can be reconstructed by microsurgical techniques. The aim of peripheral nerve surgery is to pave way for fast and most possible thorough functional recovery. However, full functional recovery is rare...

Various biomaterials have been proposed to build up scaffolds for promoting neural repair. Among them, chitosan, a derivative of chitin, has been raising more and more interest among basic and clinical scientists. A number of studies with neuronal and glial cell cultures have shown that this biomaterial has biomimetic properties, which make it a go...

Biosynthetic nerve grafts are desired as alternative to autologous nerve grafts in peripheral nerve reconstruction. Artificial nerve conduits still have their limitations and are not widely accepted in the clinical setting. Here we report an analysis of fine-tuned chitosan tubes used to reconstruct 10 mm nerve defects in the adult rat. The chitosan...

The results of this work show that the process of oriented solidification and lyophilisation is able to produce porous chitosan scaffolds with appropriate porosity and pore size for nerve regeneration. Interesting in this context are the results of statistical analysis of image analysis from SEM micrographs of uncrosslinked and UV cross-linked samp...

The development of neural cuff-electrodes requires several in vivo studies and revisions of the electrode design before the electrode is completely adapted to its target nerve. It is therefore favorable to simulate many of the steps involved in this process to reduce costs and animal testing. As the restoration of motor function is one of the most...

The growth/differentiation factor-15, GDF-15, has been found to be secreted by Schwann cells in the lesioned peripheral nervous system. To investigate whether GDF-15 plays a role in peripheral nerve regeneration, we substituted exogenous GDF-15 into 10-mm sciatic nerve gaps in adult rats and compared functional and morphological regeneration to a v...

This chapter presents fast and easy protocols to obtain highly purified cultures of proliferating adult rat, canine, and human Schwann cells. Cell preparation from predegenerated adult sciatic nerves combined with the use of melanocyte growth medium supplemented with forskolin, fibroblast growth factor-2, pituitary extract, and heregulin as selecti...

Peripheral nerve injuries are frequently seen in trauma patients and due to delayed nerve repair, lifelong disabilities often follow this type of injury. Innovative therapies are needed to facilitate and expedite peripheral nerve regeneration. The purpose of this study was to determine the effects of a 1-time topical application of a 26-amino-acid...

The polysialic acid (PSA) moiety of the neural cell adhesion molecule (NCAM) has been shown to support dynamic changes underlying peripheral nerve regeneration. Using transgenic mice expressing polysialyltransferase ST8SiaIV under control of a glial-specific (proteolipid protein, PLP) promoter (PLP-ST8SiaIV-transgenic mice), we tested the hypothesi...

The advantage of minimally invasive electrodiagnostic methods for periodic evaluation of reinnervation at predefined time intervals does not seem to be widely recognized. In this study, using a rat model, we assessed the utility of periodic electrodiagnostic measurements for monitoring ongoing motor recovery after peripheral nerve injuries of diffe...

The better the understanding of cellular and molecular events involved in nervous system degeneration and regeneration became during the last decades, the more likely have gene therapy approaches become to improve nervous system regeneration and to find their position in clinical settings. Gene therapy based strategies for neuroregeneration mainly...

Peripheral nerve research is highly dynamic and a current major focus is the development of cell based supportive therapies as well as bioengineered nerve conduits to overcome the challenges in reconstructing long peripheral nerve defects. Whenever primary nerve repair cannot be performed without regeneration impairing tension at the suture sites,...

Short-term low-frequency electrical stimulation (ESTIM) of proximal peripheral nerve stumps prior to end-to-end coaptation or tubular bridging of small distances has been reported to increase preferential motor reinnervation and functional motor recovery in animal models and human patients undergoing carpal tunnel release surgery. We investigated t...

With the aim to develop new biomaterials for peripheral nerve grafts, the current study used bioidentical polysialic acid (polySia) as complement in synthetic conduits. polySia provides an important guidance cue during nervous system development and regeneration. First in vivo results on the use of cell-free and Schwann cell-containing synthetic pe...

We compared the origin and quality of regenerating myelinated axons after end-to-side neurorrhaphy or end-to-end neurorrhaphy. Transected adult rat tibial nerves were either end-to-end coapted or the distal stump was sutured to a perineurial window of the fibular nerve. Electromyographic recordings from the gastrocnemius muscle 8 weeks later reveal...

After peripheral nerve injury, Schwann cells (SC) guarantee for a regeneration-promoting milieu and are crucially involved in axonal regeneration. For extended nerve defects, bridging with an autologous nerve transplant is the gold standard therapy. Artificial biohybrid nerve transplants which combine a synthetic conduit with autologous SC genetica...

Neurotrophic factors have been shown to stimulate and support peripheral nerve repair. One of these factors is basic fibroblast growth factor (FGF-2), which is up-regulated after peripheral nerve injury and influences early sciatic nerve regeneration by regulating Schwann cell proliferation. Our previous study on FGF-2 deficient mice indicated that...

Chronic dysregulation of the intracellular Ca(2+) homeostasis (excitotoxicity) is thought to contribute to the development of motor neuron diseases. Valproic acid (VPA) is widely used as an antiepileptic drug and acts mainly by inhibition of sodium channels and by enhancing the level of the inhibitory neurotransmitter gamma-aminobutyric acid. Neuro...

Easily applicable techniques are presented to obtain high numbers of enriched canine Schwann cells (cSC) in a short time-window. The potential of adult SC for tissue engineering of peripheral nerves and ex vivo gene therapy is obvious from physiological events taking place after peripheral nerve transection [Haastert, K., Grothe, C., 2007. Gene the...

Damages to the complex of auditory and facial nerve by surgery lead to a permanent hearing impairment and facial paralysis. To regenerate nerve fibers, scaffolds can be used for guided axonal growth. Ideally, these scaffolds should be biodegradable to avoid removal surgery in the nervous system, and adaptable to the individual lesion site. The aim...

To determine whether transplantation of Schwann cells (SCs) overexpressing different isoforms of fibroblast growth factor 2 (FGF-2) combined with manual stimulation (MS) of vibrissal muscles improves recovery after facial nerve transection in adult rat. Transected facial nerves were entubulated with collagen alone or collagen plus naïve SCs or tran...

Studies were conducted to determine the possibility that voluntary exercise could enhance regenerative effects of gene therapy via Schwann cells (SC) over-expressing FGF-2. Sedentary or exercise rehabilitation conditions were therefore provided shortly after reconstructing 10mm sciatic nerve gaps in rats with silicone grafts. Exercise for 7 days el...

According to expression studies and functional analyses in mutant mice and in rats, FGF-2 appears to be specifically involved during development of peripheral nerves and in de-/re-generating processes at the lesion site and in spinal ganglia. In the absence of FGF receptor (FGFR)3, axonal and myelin diameters of peripheral nerves are significantly...

To understand the mechanisms of remyelination and the reasons for regeneration failure is one of the major challenges in multiple sclerosis research. This requires a good knowledge and reliable analysis of experimental models. This work was undertaken to characterize the pattern of myelin protein expression during experimental remyelination. Acute...

Fibroblast growth factors (FGFs) signal via four distinct high affinity cell surface tyrosine kinase receptors, termed FGFR1-FGFR4 (FGFR-FGF-receptor). Recently, a new modulator of the FGF signaling pathway, the transmembrane protein 'similar expression to FGF genes' (Sef), has been identified in zebrafish and subsequently in mammals. Sef from mous...

Motor neuron death in amyotrophic lateral sclerosis (ALS) has been linked to selective vulnerability towards AMPA receptor-mediated excitotoxicity. We investigated intracellular mechanisms leading to impairment of motor neuron Ca2+ homeostasis with near physiological AMPA receptor activation. Using fast solution exchange on patch-clamped cultured n...