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  • 1.
    di Summa, Pietro G
    et al.
    University Hospital of Lausanne, University of Manchester.
    Kalbermatten, Daniel F
    University Hospital of Lausanne, University Hospital of Basel.
    Pralong, E
    University Hospital of Lausanne.
    Raffoul, W
    University Hospital of Lausanne.
    Kingham, Paul J
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Terenghi, Giorgio
    University of Manchester.
    Long-term in vivo regeneration of peripheral nerves through bioengineered nerve grafts2011In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 181, no 5, 278-291 p.Article in journal (Refereed)
    Abstract [en]

    Although autologous nerve graft is still the first choice strategy in nerve reconstruction, it has the severe disadvantage of the sacrifice of a functional nerve. Cell transplantation in a bioartificial conduit is an alternative strategy to improve nerve regeneration. Nerve fibrin conduits were seeded with various cell types: primary Schwann cells (SC), SC-like differentiated bone marrow-derived mesenchymal stem cells (dMSC), SC-like differentiated adipose-derived stem cells (dASC). Two further control groups were fibrin conduits without cells and autografts. Conduits were used to bridge a 1 cm rat sciatic nerve gap in a long term experiment (16 weeks). Functional and morphological properties of regenerated nerves were investigated. A reduction in muscle atrophy was observed in the autograft and in all cell-seeded groups, when compared with the empty fibrin conduits. SC showed significant improvement in axon myelination and average fiber diameter of the regenerated nerves. dASC were the most effective cell population in terms of improvement of axonal and fiber diameter, evoked potentials at the level of the gastrocnemius muscle and regeneration of motoneurons, similar to the autografts. Given these results and other advantages of adipose derived stem cells such as ease of harvest and relative abundance, dASC could be a clinically translatable route towards new methods to enhance peripheral nerve repair.

  • 2.
    di Summa, Pietro G
    et al.
    University of Manchester, University Hospital of Lausanne.
    Kalbermatten, Daniel F
    University Hospital of Basel.
    Raffoul, Wassim
    University Hospital of Lausanne.
    Terenghi, Giorgio
    University of Manchester.
    Kingham, Paul J
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. University of Manchester.
    Extracellular matrix molecules enhance the neurotrophic effect of Schwann cell-like differentiated adipose-derived stem cells and increase cell survival under stress conditions2013In: Tissue Engineering. Part A, ISSN 1937-3341, E-ISSN 1937-335X, Vol. 19, no 3-4, 368-379 p.Article in journal (Refereed)
    Abstract [en]

    Since the first reports of induction of adipose-derived stem cells (ASC) into neuronal and glial cell phenotypes, expectations have increased regarding their use in tissue engineering applications for nerve repair. Cell adhesion to extracellular matrix (ECM) is a basic feature of survival, differentiation, and migration of Schwann cells (SC) during nerve regeneration, and fibronectin and laminin are two key molecules of this process. Interaction between ECM and SC-like differentiated ASC (dASC) could potentially improve the neurotrophic potential of the stem cells. We have investigated the effect of ECM molecules on SC-like dASC in terms of proliferation, adhesion, and cell viability. Fibronectin and laminin did not affect the proliferation of dASC when compared with cell adherent tissue culture plastic, but significantly improved viability and cell attachment when dASC were exposed to apoptotic conditions. To assess the influence of the ECM molecules on dASC neurotrophic activity, dASC were seeded onto ECM-coated culture inserts suspended above dorsal root ganglia (DRG) sensory neurons. Neurite outgrowth of DRG neurons was enhanced when dASC were seeded on fibronectin and laminin when compared with controls. When DRG neurons and dASC were in direct contact on the various surfaces there was significantly enhanced neurite outgrowth and coculture with laminin-conditioned dASC produced the longest neurites. Compared with primary SCs, dASC grown on laminin produced similar levels of neurite outgrowth in the culture insert experiments but neurite length was shorter in the direct contact groups. Anti beta 1 integrin blocking antibody could inhibit baseline and dASC evoked neurite elongation but had no effect on outgrowth mediated by laminin-conditioned dASC. ECM molecules had no effect on the levels of nerve growth factor and brain-derived neurotrophic factor secretion from dASC. The results of the study suggest that ECM molecules can significantly improve the potential of dASC for nerve regeneration.

  • 3.
    di Summa, Pietro G
    et al.
    Department of Plastic, Reconstructive Surgery, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland. Electronic address: Pietro.Di-Summa@chuv.ch..
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Campisi, Corrado C
    Department of Plastic, Reconstructive Surgery, University Hospital of Genova, Ospedale S. Martino, Largo Rossana Benzi 10, 16132 Genova, Italy.
    Raffoul, Wassim
    Department of Plastic, Reconstructive Surgery, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland.
    Kalbermatten, Daniel F
    Department of Plastic, Reconstructive Surgery, University Hospital of Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland.
    Collagen (NeuraGen(®)) nerve conduits and stem cells for peripheral nerve gap repair2014In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 572, 26-31 p.Article in journal (Refereed)
    Abstract [en]

    Collagen nerve guides are used clinically for peripheral nerve defects, but their use is generally limited to lesions up to 3cm. In this study we combined collagen conduits with cells as an alternative strategy to support nerve regeneration over longer gaps. In vitro cell adherence to collagen conduits (NeuraGen(®) nerve guides) was assessed by scanning electron microscopy. For in vivo experiments, conduits were seeded with either Schwann cells (SC), SC-like differentiated bone marrow-derived mesenchymal stem cells (dMSC), SC-like differentiated adipose-derived stem cells (dASC) or left empty (control group), conduits were used to bridge a 1cm gap in the rat sciatic nerve and after 2-weeks immunohistochemical analysis was performed to assess axonal regeneration and SC infiltration. The regenerative cells showed good adherence to the collagen walls. Primary SC showed significant improvement in distal stump sprouting. No significant differences in proximal regeneration distances were noticed among experimental groups. dMSC and dASC-loaded conduits showed a diffuse sprouting pattern, while SC-loaded showed an enhanced cone pattern and a typical sprouting along the conduits walls, suggesting an increased affinity for the collagen type I fibrillar structure. NeuraGen(®) guides showed high affinity of regenerative cells and could be used as efficient vehicle for cell delivery. However, surface modifications (e.g. with extracellular matrix molecule peptides) of NeuraGen(®) guides could be used in future tissue-engineering applications to better exploit the cell potential.

  • 4.
    di Summa, Pietro G
    et al.
    Chirurgie Plastique et Reconstructive CHUV, Université de Lausanne, Rue de Bugnon 46, 1005 Lausanne, CH, Switzerland.
    Kingham, Paul J
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Raffoul, W
    Chirurgie Plastique et Reconstructive CHUV, Université de Lausanne, Rue de Bugnon 46, 1005 Lausanne, CH, Switzerland.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Terenghi, Giorgio
    Blond McIndoe Research Laboratories. The University of Manchester, Manchester, UK.
    Kalbermatten, Daniel F
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Adipose-derived stem cells enhance peripheral nerve regeneration2010In: Journal of plastic, reconstructive and aesthetic surgery, ISSN 1878-0539, Vol. 63, no 9, 1544-1552 p.Article in journal (Refereed)
    Abstract [en]

    Traumatic injuries resulting in peripheral nerve lesions often require a graft to bridge the gap. Although autologous nerve auto-graft is still the first-choice strategy in reconstructions, it has the severe disadvantage of the sacrifice of a functional nerve. Cell transplantation in a bioartificial conduit is an alternative strategy to create a favourable environment for nerve regeneration. We decided to test new fibrin nerve conduits seeded with various cell types (primary Schwann cells and adult stem cells differentiated to a Schwann cell-like phenotype) for repair of sciatic nerve injury. Two weeks after implantation, the conduits were removed and examined by immunohistochemistry for axonal regeneration (evaluated by PGP 9.5 expression) and Schwann cell presence (detected by S100 expression). The results show a significant increase in axonal regeneration in the group of fibrin seeded with Schwann cells compared with the empty fibrin conduit. Differentiated adipose-derived stem cells also enhanced regeneration distance in a similar manner to differentiated bone marrow mesenchymal stem cells. These observations suggest that adipose-derived stem cells may provide an effective cell population, without the limitations of the donor-site morbidity associated with isolation of Schwann cells, and could be a clinically translatable route towards new methods to enhance peripheral nerve repair.

  • 5. di Summa, Pietro G
    et al.
    Raffoul, Wassim
    Kalbermatten, Daniel F
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Plastic Surgery, CHUV, University of Lausanne, Lausanne, Switzerland.
    Paper clip microretractor2009In: Journal of reconstructive microsurgery, ISSN 0743-684X, E-ISSN 1098-8947, Vol. 25, no 4, 273-273 p.Article in journal (Other academic)
  • 6.
    Engels, Patricia E.
    et al.
    University Hospital Basel.
    Tremp, Mathias
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    di Summa, Pietro G.
    Largo, Rene D.
    Schaefer, Dirk J.
    Kalbermatten, Daniel F
    Harvest site influences the growth properties of adipose derived stem cells2013In: Cytotechnology (Dordrecht), ISSN 0920-9069, E-ISSN 1573-0778, Vol. 65, no 3, 437-445 p.Article in journal (Refereed)
    Abstract [en]

    The therapeutic potential of adult stem cells may become a relevant option in clinical care in the future. In hand and plastic surgery, cell therapy might be used to enhance nerve regeneration and help surgeons and clinicians to repair debilitating nerve injuries. Adipose-derived stem cells (ASCs) are found in abundant quantities and can be harvested with a low morbidity. In order to define the optimal fat harvest location and detect any potential differences in ASC proliferation properties, we compared biopsies from different anatomical sites (inguinal, flank, pericardiac, omentum, neck) in Sprague-Dawley rats. ASCs were expanded from each biopsy and a proliferation assay using different mitogenic factors, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) was performed. Our results show that when compared with the pericardiac region, cells isolated from the inguinal, flank, omental and neck regions grow significantly better in growth medium alone. bFGF significantly enhanced the growth rate of ASCs isolated from all regions except the omentum. PDGF had minimal effect on ASC proliferation rate but increases the growth of ASCs from the neck region. Analysis of all the data suggests that ASCs from the neck region may be the ideal stem cell sources for tissue engineering approaches for the regeneration of nervous tissue.

  • 7.
    Erba, P
    et al.
    University of Manchester, University Hospital of Basel.
    Mantovani, Cristina
    University of Manchester.
    Kalbermatten, Daniel F
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pierer, G
    University Hospital of Basel.
    Terenghi, Giorgio
    University of Manchester.
    Kingham, Paul J
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Regeneration potential and survival of transplanted undifferentiated adipose tissue-derived stem cells in peripheral nerve conduits2010In: Journal of plastic, reconstructive & aesthetic surgery : JPRAS, ISSN 1878-0539, Vol. 63, no 12, e811-e817 p.Article in journal (Refereed)
    Abstract [en]

    Adipose tissue-derived stem cells (ADSCs) have shown potential for the treatment of nerve injuries. Most previous efforts have aimed at stimulating regeneration by using neural-differentiation protocols, but the potential of undifferentiated ADSCs to enhance axonal growth as well as their ability to transdifferentiate in situ have been poorly investigated. In this study, using a rat sciatic nerve model we show that ADSCs, transplanted in an artificial nerve conduit, stimulate axonal outgrowth from the proximal nerve stump and evoke greater Schwann cell (SC) proliferation/intrusion in the distal stump. To track the fate of the transplanted cells, we used green fluorescent protein (GFP)-labelling and polymerase chain reaction (PCR) for the detection of the sex determining region Y (SRY) gene in the donor male cells. Both methods indicated a lack of significant quantities of viable cells 14 days after transplantation. These results suggest that any regenerative effect of transplanted ADSCs is more likely to be mediated by an initial boost of released growth factors and/or by an indirect effect on endogenous SCs activity. Future studies need to address long-term cell survival in tissue-engineered nerve conduits to improve the neuroregenerative potential of ADSCs.

  • 8. Erba, P
    et al.
    Wettstein, R
    Tolnay, M
    Rieger, UM
    Pierer, G
    Kalbermatten, Daniel F
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital of Basel, CH-4031 Basel, Switzerland.
    Neurocutaneous sural flap in paraplegic patients2009In: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1532-1959, Vol. 62, no 8, 1094-1098 p.Article in journal (Refereed)
    Abstract [en]

    Neurocutaneous flaps have been demonstrated to be a reliable option in different groups of patients but it remains unclear if distally-based sural flaps can be safety used in paraplegic patients because they suffer from significant nervous system alterations. The aim of this proof-of-concept study is to demonstrate that these flaps are reliable in paraplegic patients. We prospectively analysed a group (n = 6) of paraplegic patients who underwent reversed sural flap surgery for ulcers on the lateral malleolus. Measurement of area and photographic documentation techniques have been employed to quantify the defect area. Sural nerve biopsies have been analysed histologically with several different staining techniques to assess the neurovascular network and the myelinisation of the nerve. The patients showed uneventful wound heating, except one case that suffered a partial flap necrosis that heated by secondary intention. Histologic analysis revealed an intact neurovascular network and myelinated nerve fibres. In this small series of paraplegic patients that underwent a distally-based sural flap, the complication rate was low, with only one case of superficial partial necrosis demonstrating the reliability and safety of the flap in this subset of patients. Histologic evaluation of sural. nerve biopsies revealed an almost normal morphology. A possible explanation of this phenomenon is that the dorsal root ganglia remain intact in paraplegic patients and can preserve neural characteristics in the peripheral sensory nerve system.

  • 9.
    Kalbermatten, Daniel
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Nerve gap repair by the use of artificial conduits and cultured cells2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Peripheral nerve injuries are often associated with loss of nerve tissue and require autologous nerve grafts to provide a physical substrate for axonal growth. This thesis investigates the use of fibrin as both a tubular conduit to guide nerve regeneration and also as a matrix material to suspend various regenerative cell types within/on poly-3-hydroxybutyrate (PHB) nerve conduits. Adipose derived stem cells (ASC) are found in abundant quantities. In this thesis the ability of rat ASC to differentiate into Schwann cells was determined and a preliminary study of the neurotrophic potential of human ASC was also investigated.

    Rat sciatic nerve axotomy was performed proximally in the thigh to create a 10-mm gap between the nerve stumps and the gap was bridged using the various conduits.  At early time points the nerve grafts were harvested and investigated for axonal and Schwann cell markers.  After 16 weeks the regenerative response from sensory and motor neurons was also evaluated following retrograde labelling with Fast Blue fluorescent tracer. Stem cells were treated with a mixture of glial growth factors and after 2 weeks in vitro the expression of Schwann cell markers was analysed by immunocytochemistry and Western blotting.  ASC were cocultured with the NG108-15 neuronal cell line to determine their ability to promote neurite outgrowth.  Human ASC were isolated from the deep and superficial layers of abdominal fat tissue obtained during abdominoplasty procedures.  RT-PCR was used to investigate the expression of neurotrophic factors.

    Immunohistochemistry showed a superior nerve regeneration distance in the fibrin conduit compared with PHB. The fibrin conduit promoted regeneration of 60% of sensory neurones and 52% of motor neurones when compared with an autograft group at 16 weeks. The total number of myelinated axons in the distal nerve stump in the fibrin-conduit group reached 86% of the graft and the weight of gastrocnemius and soleus muscles recovered to 82% and 89% of the controls, respectively. In vitro studies showed that rat ASC could be differentiated to a Schwann cell phenotype. These treated cells enhanced both the number of NG108-15 cells expressing neurites and neurite length. In the same coculture model system, human superficial fat layer ASC induced significantly enhanced neurite outgrowth when compared with the deep layer fat cells. RT-PCR analysis showed ASC isolated from both layers expressed neurotrophic factors.

    These results indicate that a tubular fibrin conduit can be used to promote neuronal regeneration following peripheral nerve injury. There was also a beneficial effect of using a fibrin matrix to seed cells within/on PHB conduits which should ultimately lead to improved functional recovery following nerve injury.  There might also be an advantage to use a simple strip of PHB rather than a conventional tube-like structure implying that single fascicle nerve grafting could be advantageous for nerve repair.  The results of in vitro experiments indicate adipose tissue contains a pool of regenerative stem cells which can be differentiated to a Schwann cell phenotype and given that human ASC express a range of neurotrophic factors they are likely to be of clinical benefit for treatment of peripheral nerve injuries.

  • 10.
    Kalbermatten, Daniel F
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Erba, P
    Mahay, Daljeet
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Pierer, Gerhard
    Terenghi, Giorgio
    Schwann cell strip for peripheral nerve repair2008In: Journal of Hand Surgery - British and European Volume, ISSN 0266-7681, E-ISSN 1532-2211, Vol. 33, no 5, 587-594 p.Article in journal (Refereed)
    Abstract [en]

    Many strategies have been investigated to provide an ideal substitute to treat a nerve gap injury. Initially, silicone conduits were used and more recently conduits fabricated from natural materials such as poly-3-hydroxybutyrate (PHB) showed good results but still have their limitations. Surgically, a new concept optimising harvested autologous nerve graft has been introduced as the single fascicle method. It has been shown that a single fascicle repair of nerve grafting is successful. We investigated a new approach using a PHB strip seeded with Schwann cells to mimic a small nerve fascicle. Schwann cells were attached to the PHB strip using diluted fibrin glue and used to bridge a 10-mm sciatic nerve gap in rats. Comparison was made with a group using conventional PHB conduit tubes filled with Schwann cells and fibrin glue. After 2 weeks, the nerve samples were harvested and investigated for axonal and Schwann cell markers. PGP9.5 immunohistochemistry showed a superior nerve regeneration distance in the PHB strip group versus the PHB tube group (> 10 mm, crossed versus 3.17+/- 0.32 mm respectively, P<0.05) as well as superior Schwann cell intrusion (S100 staining) from proximal (> 10 mm, crossed versus 3.40+/- 0.36 mm, P<0.01) and distal (> 10 mm, crossed versus 2.91+/- 0.31 mm, P<0.001) ends. These findings suggest a significant advantage of a strip in rapidly connecting a nerve gap lesion and imply that single fascicle nerve grafting is advantageous for nerve repair in rats.

  • 11.
    Kalbermatten, Daniel F
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kingham, Paul J
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Mahay, Daljeet
    Mantovani, Cristina
    Pettersson, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Raffoul, W
    Balcin, H
    Pierer, G
    Terenghi, Giorgio
    Fibrin matrix for suspension of regenerative cells in an artificial nerve conduit2008In: Journal of plastic, reconstructive and aesthetic surgery, ISSN 1878-0539, Vol. 61, no 6, 669-675 p.Article in journal (Refereed)
    Abstract [en]

    Peripheral nerve injury presents with specific problems of neuronal reconstructions, and from a clinical viewpoint a tissue engineering approach would facilitate the process of repair and regeneration. We have previously used artificial nerve conduits made from bioresorbable poly-3-hydroxybutyrate (PHB) in order to refine the ways in which peripheral nerves are repaired and reconnected to the target muscles and skin. The addition of Schwann cells (SC) or differentiated mesenchymal stem cells (dMSC) to the conduits enhances regeneration. In this study, we have used a matrix based on fibrin (Tisseel) to fill optimally the nerve-conduits with cells. In vitro analysis showed that both SC and MSC adhered significantly better to PHB in the presence of fibrin and cells continued to maintain their differentiated state. Cells were more optimally distributed throughout the conduit when seeded in fibrin than by delivery in growth medium alone. Transplantation of the nerve conduits in vivo showed that cells in combination with fibrin matrix significantly increased nerve regeneration distance (using PGP9.5 and S100 distal and proximal immunohistochemistry) when compared with empty PHB conduits. This study shows the beneficial combinatory effect of an optimised matrix, cells and conduit material as a step towards bridging nerve gaps which should ultimately lead to improved functional recovery following nerve injury.

  • 12.
    Kalbermatten, Daniel F
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pettersson, Jonas
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kingham, Paul J
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pierer, Gerhard
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Terenghi, Giorgio
    New fibrin conduit for peripheral nerve repair2009In: Journal of reconstructive microsurgery, ISSN 0743-684X, E-ISSN 1098-8947, Vol. 25, no 1, 27-33 p.Article in journal (Refereed)
    Abstract [en]

    An ideal substitute to treat a nerve gap has not been found. Initially, silicone conduits were employed. Later, conduits were fabricated from collagen or polyesters carbonates. More recently, it has been shown that a bioresorbable material, poly-3-hydroxybutyrate (PHB), can enhance nerve repair. The present investigation shows the use of fibrin as a conduit to guide nerve regeneration and bridge nerve defects. In this study we prepared and investigated a novel nerve conduit made from fibrin glue. Using a rodent sciatic nerve injury model (10-mm gap), we compared the extent of nerve regeneration through the new fibrin conduits versus established PHB conduits. After 2 and 4 weeks, conduits containing proximal and distal stumps were harvested. We evaluated the initial axon and Schwann cell stimulation using immunohistochemistry. The conduits presented full tissue integration and were completely intact. Axons crossed the gap after 1 month. Immunohistochemistry using the axonal marker PGP 9.5 showed a superior nerve regeneration distance in the fibrin conduit compared with PHB (4.1 mm versus 1.9 mm). Schwann cell intrusion (S100 staining) was similarly enhanced in the fibrin conduits, both from the proximal (4.2 mm versus 2.1 mm) and distal ends (3.2 mm versus 1.7 mm). These findings suggest an advantage of the new fibrin conduit for the important initial phase of peripheral nerve regeneration. The use of fibrin glue as a conduit is a step toward a usable graft to bridge peripheral nerve lesions. This might be clinically interesting, given the widespread acceptance of fibrin glue among the surgical community.

  • 13.
    Kalbermatten, Daniel F
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Schaakxs, Dominique
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kingham, Paul J
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Neurotrophic activity of human adipose stem cells isolated from deep and superficial layers of abdominal fat2011In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 344, no 2, 251-260 p.Article in journal (Refereed)
    Abstract [en]

    New approaches to the clinical treatment of traumatic nerve injuries may one day utilize stem cells to enhance nerve regeneration. Adipose-derived stem cells (ASC) are found in abundant quantities and can be harvested by minimally invasive procedures that should facilitate their use in such regenerative applications. We have analyzed the properties of human ASC isolated from the deep and superficial layers of abdominal fat tissue obtained during abdominoplasty procedures. Cells from the superficial layer proliferate significantly faster than those from the deep layer. In both the deep and superficial layers, ASC express the pluripotent stem cell markers oct4 and nanog and also the stro-1 cell surface antigen. Superficial layer ASC induce the significantly enhanced outgrowth of neurite-like processes from neuronal cell lines when compared with that of deep layer cells. However, analysis by reverse transcription with the polymerase chain reaction and by enzyme-linked immunosorbent assay has revealed that ASC isolated from both layers express similar levels of the following neurotrophic factors: nerve growth factor, brain-derived neurotrophic factor and glial-derived neurotrophic factor. Thus, human ASC show promising potential for the treatment of traumatic nerve injuries. In particular, superficial layer ASC warrant further analysis of their neurotrophic molecules.

  • 14.
    Kalbermatten, Daniel F
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Wettstein, Reto
    vonKanel, Oliver
    Erba, Paolo
    Pierer, Gerhard
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Haug, Martin
    Sensate lateral arm flap for defects of the lower leg.2008In: Annals of plastic surgery, ISSN 1536-3708, Vol. 61, no 1, 40-6 p.Article in journal (Refereed)
    Abstract [en]

    Ideally, reconstruction of lower extremity soft tissue defects includes not only an esthetically pleasing 3-dimensional shape and solid anchoring to the underlying structures to resist shear forces, but should also address the restoration of sensation. Therefore, we present a prospective study on defect reconstruction of the lower leg and ankle to evaluate the role of sensate free fasciocutaneous lateral arm flap and the impact of sensory nerve reconstruction. Thirty patients were allocated randomly to the study group (n = 15) that obtained end-to-side sensate coaptation using the lower lateral cutaneous brachial nerve to the tibial nerve using the epineural window technique, or to the control group reconstructed without nerve coaptation. At 1-year follow-up the patients were evaluated for pain sensation, thermal sensibility, static and moving 2-point discrimination, and Semmes-Weinstein monofilament tests. Data from both groups were compared and statistically analyzed with the Mann-Whitney U test and the Fisher exact test. Flaps of the study group reached a static and moving 2-point discrimination and Semmes-Weinstein monofilament tests nearly equal to the contralateral leg area and significantly better than flaps of the control group. Donor damage morbidity of the tibial nerve did not occur. To our point of view resensation should be carried out by end-to-side neurorrhaphy to the tibial nerve because of the superior restoration of sensibility.

  • 15.
    Kalbermatten, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Schaakxs, Dominique
    Kingham, Paul
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Neurotrophic activity of human adipose stem cells isolated from deep and superficial layers of abdominal fatManuscript (preprint) (Other academic)
    Abstract [en]

    New approaches to the clinical treatment of traumatic nerve injuries may one day utilize stem cells to enhance nerve regeneration.  Adipose derived stem cells (ASC) are found in abundant quantities and can be harvested by minimally invasive procedures which should facilitate their use in such regenerative applications.  In this study, we have analyzed the properties of human ASC isolated from the deep and superficial layers of abdominal fat tissue obtained during abdominoplasty procedures.  Cells from the superficial layer proliferated significantly faster than those from the deep layer. Both in the deep and superficial layers, ASC expressed the pluripotent stem cell markers oct4 and nanog and also the stro-1 cell surface antigen.  Superficial layer ASC induced significantly enhanced neurite outgrowth from NG108-15 motor neuron like cells when compared with the deep layer cells.  However, RT-PCR analysis showed that ASC isolated from both layers expressed similar levels of the neurotrophic factors NGF, BDNF, GDNF and NT-3.  These results indicate that human ASC have promising potential for the treatment of traumatic nerve injuries and that superficial layer ASC might represent the more optimal cell type for such applications.

  • 16. Kingham, Paul J
    et al.
    Kalbermatten, Daniel F
    Mahay, Daljeet
    Armstrong, Stephanie J
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Terenghi, Giorgio
    Adipose-derived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro.2007In: Exp Neurol, ISSN 0014-4886, Vol. 207, no 2, 267-74 p.Article in journal (Refereed)
    Abstract [en]

    Experimentally, peripheral nerve repair can be enhanced by Schwann cell transplantation but the clinical application is limited by donor site morbidity and the inability to generate a sufficient number of cells quickly. We have investigated whether adult stem cells, isolated from adipose tissue, can be differentiated into functional Schwann cells. Rat visceral fat was enzymatically digested to yield rapidly proliferating fibroblast-like cells, a proportion of which expressed the mesenchymal stem cell marker, stro-1, and nestin, a neural progenitor protein. Cells treated with a mixture of glial growth factors (GGF-2, bFGF, PDGF and forskolin) adopted a spindle-like morphology similar to Schwann cells. Immunocytochemical staining and western blotting indicated that the treated cells expressed the glial markers, GFAP, S100 and p75, indicative of differentiation. When co-cultured with NG108-15 motor neuron-like cells, the differentiated stem cells enhanced the number of NG108-15 cells expressing neurites, the number of neurites per cell and the mean length of the longest neurite extended. Schwann cells evoked a similar response whilst undifferentiated stem cells had no effect. These results indicate adipose tissue contains a pool of regenerative stem cells which can be differentiated to a Schwann cell phenotype and may be of benefit for treatment of peripheral nerve injuries.

  • 17.
    Pettersson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kalbermatten, Daniel
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    McGrath, Aleksandra
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Novikova, Liudmila N
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Biodegradable fibrin conduit promotes long-term regeneration after peripheral nerve injury in adult rats2010In: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1532-1959, Vol. 63, no 11, 1893-1899 p.Article in journal (Refereed)
    Abstract [en]

    Peripheral nerve injuries are often associated with loss of nerve tissue and require autologous nerve grafts to provide a physical substrate for axonal growth. Biosynthetic neural conduits could be an alternative treatment strategy in such injuries. The present study investigates the long-term effects of a tubular fibrin conduit on neuronal regeneration, axonal sprouting and recovery of muscle weight following peripheral nerve injury and repair in adult rats. Sciatic axotomy was performed proximally in the thigh to create a 10-mm gap between the nerve stumps. The injury gap was bridged by using a 14-mm-long fibrin glue conduit, entubulating 2mm of the nerve stump at each end. A reversed autologous nerve graft was used as a control. The regenerative response from sensory and motor neurones was evaluated following retrograde labelling with Fast Blue fluorescent tracer. In control experiments, at 16 weeks following peripheral nerve grafting, 5184 (+/-574 standard error of mean (SEM)) sensory dorsal root ganglion neurones and 1001 (+/-37 SEM) spinal motor neurones regenerated across the distal nerve-graft interface. The fibrin conduit promoted regeneration of 60% of sensory neurones and 52% of motor neurones when compared to the control group. The total number of myelinated axons in the distal nerve stump in the fibrin-conduit group reached 86% of the control and the weight of gastrocnemius and soleus muscles recovered to 82% and 89% of the controls, respectively. The present results suggest that a tubular fibrin conduit can be used to promote neuronal regeneration following peripheral nerve injury.

  • 18.
    Pettersson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    McGrath, Aleksandra
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Kalbermatten, Daniel
    University Hospital of Basel.
    Novikova, Liudmila
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Kingham, Paul
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Novikov, Lev
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Muscle recovery after repair of short and long peripheral nerve gaps using fibrin conduits2011In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 500, no 1, 41-46 p.Article in journal (Refereed)
    Abstract [en]

    Peripheral nerve injuries with loss of nervous tissue are a significant clinical problem and are currently treated using autologous nerve transplants. To avoid the need for donor nerve, which results in additional morbidity such as loss of sensation and scarring, alternative bridging methods have been sought. Recently we showed that an artificial nerve conduit moulded from fibrin glue is biocompatible to nerve regeneration. In this present study, we have used the fibrin conduit or a nerve graft to bridge either a 10 mm or 20 mm sciatic nerve gap and analyzed the muscle recovery in adult rats after 16 weeks. The gastrocnemius muscle weights of the operated side were similar for both gap sizes when treated with nerve graft. In contrast, muscle weight was 48.32 ± 4.96% of the contra-lateral side for the 10 mm gap repaired with fibrin conduit but only 25.20 ± 2.50% for the 20 mm gap repaired with fibrin conduit. The morphology of the muscles in the nerve graft groups showed an intact, ordered structure, with the muscle fibers grouped in fascicles whereas the 20 mm nerve gap fibrin group had a more chaotic appearance. The mean area and diameter of fast type fibers in the 20 mm gap repaired with fibrin conduits were significantly (P < 0.01) worse than those of the corresponding 10 mm gap group. In contrast, both gap sizes treated with nervegraft showed similar fiber size. Furthermore, the 10 mm gaps repaired with either nerve graft or fibrin conduit showed similar muscle fiber size. These results indicate that the fibrin conduit can effectively treat short nerve gaps but further modification such as the inclusion of regenerative cells may be required to attain the outcomes of nerve graft for long gaps.

  • 19.
    Schaakxs, Dominique
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Division of Plastic, Reconstructive and Aesthetic Surgery, CHUV, University Hospital of Lausanne, Switzerland.
    Kalbermatten, Daniel F
    Pralong, Etienne
    Raffoul, Wassim
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Kingham, Paul J
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Poly-3-hydroxybutyrate strips seeded with regenerative cells are effective promoters of peripheral nerve repair2017In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 11, no 3, 812-821 p.Article in journal (Refereed)
    Abstract [en]

    Peripheral nerve injuries are often associated with loss of nerve tissue and require a graft to bridge the gap. Autologous nerve grafts are still the 'gold standard' in reconstructive surgery but have several disadvantages, such as sacrifice of a functional nerve, neuroma formation and loss of sensation at the donor site. Bioengineered grafts represent a promising approach to address this problem. In this study, poly-3-hydroxybutyrate (PHB) strips were used to bridge a 10 mm rat sciatic nerve gap and their effects on long-term (12 weeks) nerve regeneration were compared. PHB strips were seeded with different cell types, either primary Schwann cells (SCs) or SC-like differentiated adipose-derived stem cells (dASCs) suspended in a fibrin glue matrix. The control group was PHB and fibrin matrix without cells. Functional and morphological properties of the regenerated nerve were assessed using walking track analysis, EMGs, muscle weight ratios and muscle and nerve histology. The animals treated with PHB strips seeded with SCs or dASCs showed significantly better functional ability than the control group. This correlated with less muscle atrophy and greater axon myelination in the cell groups. These findings suggest that the PHB strip seeded with cells provides a beneficial environment for nerve regeneration. Furthermore, dASCs, which are abundant and easily accessible, constitute an attractive cell source for future applications of cell therapy for the clinical repair of traumatic nerve injuries.

  • 20.
    Schaakxs, Dominique
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. University Hospital of Lausanne.
    Kalbermatten, Daniel F
    University Hospital of Basel.
    Raffoul, Wassim
    University Hospital of Lausanne.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Regenerative cell injection in denervated muscle reduces atrophy and enhances recovery following nerve repair2013In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 47, no 5, 691-701 p.Article in journal (Refereed)
    Abstract [en]

    Introduction: Functional muscle recovery after peripheral nerve injury is far from optimal, partly due to atrophy of the muscle arising from prolonged denervation. We hypothesized that injecting regenerative cells into denervated muscle would reduce this atrophy. Methods: A rat sciatic nerve lesion was performed, and Schwann cells or adipose-derived stem cells, untreated or induced to a Schwann-celllike phenotype (dASC), were injected into the gastrocnemius muscle. Nerves were either repaired immediately or capped to prevent muscle reinnervation. One month later, functionality was measured using a walking track test, and muscle atrophy was assessed by examining muscle weight and histology. Results: Schwann cells and dASC groups showed significantly better scores on functional tests when compared with injections of growth medium alone. Muscle weight and histology were also significantly improved in these groups. Conclusion: Cell injections may reduce muscle atrophy and could benefit nerve injury patients.

  • 21.
    Schaakxs, Dominique
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Plastic and Reconstructive Surgery (CHUV), University Hospital of Lausanne, Lausanne, Switzerland.
    Raffoul, Wassim
    Plastic and Reconstructive Surgery (CHUV), University Hospital of Lausanne, Lausanne, Switzerland.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Kingham, Paul
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kalbermatten, Daniel
    Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital of Basel, Switzerland.
    A comparison of an artificial nerve repair construct and nerve grafting when used in combination with intramuscular injections of stem cells for reduction of muscle atrophyManuscript (preprint) (Other academic)
    Abstract [en]

    Peripheral nerve injuries represent a clinical challenge, especially when they are accompanied by loss of neural tissue. We tried to attain a better outcome after a peripheral nerve injury (in a rat sciatic nerve experimental model) by both repairing the nerve lesion and treating the denervated muscle at the same time.  We compared artificial nerve constructs made from strips of poly-3-hydroxybutyrate (PHB), seeded with or without Schwann cell-like differentiated adipose stem cells (dASC), and autografts (reverse sciatic nerve grafts) in combination with stem cell injections in the gastrocnemius muscle. dASC expressed Schwann cell markers (GFAP, S100B and p75-NTR) and secreted a range of nerve, angiogenic and muscle growth factors. Six weeks after nerve injury, the effects of the stem cells on nerve regeneration and reduction of muscle atrophy were assessed. PHB strips showed a high number of βIII-tubulin positive axons entering the distal stump and abundant endothelial cells. Animals treated with PHB strips without cells in combination with control growth medium intramuscular injections showed significantly more atrophy than the other groups.  Best results were obtained in the autograft group combined with intramuscular stem cell injections. This bioengineering research is a promising approach to treat nerve lesions and associated muscle atrophy.

  • 22.
    Schaakxs, Dominique
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Plastic and Reconstructive Surgery (CHUV), University Hospital of Lausanne, Lausanne, Switzerland.
    Vermeille, Matthieu
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital of Basel, Switzerland.
    Kalbermatten, Daniel
    Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital of Basel, Switzerland.
    Raffoul, Wassim
    Plastic and Reconstructive Surgery (CHUV), University Hospital of Lausanne, Switzerland.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Kingham, Paul
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Mechanisms of adipose stem cell interactions with muscle cells and Schwann cellsManuscript (preprint) (Other academic)
    Abstract [en]

    Peripheral nerve injury leads to muscle atrophy due to prolonged denervation. In a previous study, we showed the benefits of injecting Schwann cell and Schwann cell-like differentiated adipose stem cells (dASC) into the muscle to help nerve regeneration and prevent muscle atrophy. In this in vitro study, we have analyzed the possible mechanisms of how adipose stem cells interact with muscle cells and Schwann cells. Myoblast cell lines (C2C12 and L6) or rat primary Schwann cells treated with conditioned media prepared from either undifferentiated adipose stem cells or dASC proliferated more than control cultures. Stem cell mediated proliferation of myoblasts and Schwann cells was blocked by the inhibition of MAP kinase signaling (using U0126 drug) whereas the PKA pathway (inhibited with H89 drug) was only involved in myoblast proliferation. In order to assess the direct interaction of the stem cells with the muscle, we established direct in vitro co-culture of L6 myoblasts and stem cells for 2 weeks.  Under these conditions a small fraction of cells fused together forming multi-nucleated elongated structures, characteristic of myotubes.  These structures stained positive for fast type myosin heavy chain protein and myogenin. These effects were most pronounced in the dASC-myoblast co-cultures. ELISA analysis of the co-cultures showed high levels of secreted vascular endothelial growth factor-A (VEGF-A) and insulin like growth factor 1 proteins. Western blot analysis of denervated rat muscle tissue also showed elevated levels of VEGF-A expression in animals treated with stem cell injections. In conclusion, this study provides evidence of possible mechanisms how stem cells might influence cells of the neuromuscular system and supports the beneficial effect of using these cells for future clinical application in treatment of peripheral nerve injuries.

  • 23.
    Tremp, Mathias
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Schwabedissen, Moritz Meyer zu
    Kappos, Elisabeth A.
    Engels, Patricia E.
    Fischmann, Arne
    Scherberich, Arnaud
    Schaefer, Dirk J.
    Kalbermatten, Daniel F
    The Regeneration Potential After Human and Autologous Stem Cell Transplantation in a Rat Sciatic Nerve Injury Model Can Be Monitored by MRI2015In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 24, no 2, 203-211 p.Article in journal (Refereed)
    Abstract [en]

    Traumatic nerve injuries are a major clinical challenge. Tissue engineering using a combination of nerve conduits and cell-based therapies represents a promising approach to nerve repair. The aim of this study was to examine the regeneration potential of human adipose-derived stem cells (hASCs) after transplantation in a nonautogenous setting and to compare them with autogenous rat ASCs (rASCs) for early peripheral nerve regeneration. Furthermore, the use of MRI to assess the continuous process of nerve regeneration was elaborated. The sciatic nerve injury model in female Sprague Dawley rats was applied, and a 10-mm gap created by using a fibrin conduit seeded with the following cell types: rASCs, Schwann cell (SC)-like cells from rASC, rat SCs (rSCs), hASCs from the superficial and deep abdominal layer, as well as human stomal vascular fraction (1 x 10(6) cells). As a negative control group, culture medium only was used. After 2 weeks, nerve regeneration was assessed by immunocytochemistry. Furthermore, MRI was performed after 2 and 4 weeks to monitor nerve regeneration. Autogenous ASCs and SC-like cells led to accelerated peripheral nerve regeneration, whereas the human stem cell groups displayed inferior results. Nevertheless, positive trends could be observed for hASCs from the deep abdominal layer. By using a clinical 3T MRI scanner, we were able to visualize the graft as a small black outline and small hyperintensity indicating the regenerating axon front. Furthermore, a strong correlation was found between the length of the regenerating axon front measured by MRI and the length measured by immunocytochemistty (r= 0.74, p = 0.09). We successfully transplanted and compared human and autologous stem cells for peripheral nerve regeneration in a rat sciatic nerve injury model. Furthermore, we were able to implement the clinical 3T MRI scanner to monitor the efficacy of cellular therapy over time.

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