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Kalbermatten, Daniel F
Alternative names
Publications (10 of 23) Show all publications
Schaakxs, D., Kalbermatten, D. F., Pralong, E., Raffoul, W., Wiberg, M. & Kingham, P. J. (2017). Poly-3-hydroxybutyrate strips seeded with regenerative cells are effective promoters of peripheral nerve repair. Journal of Tissue Engineering and Regenerative Medicine, 11(3), 812-821
Open this publication in new window or tab >>Poly-3-hydroxybutyrate strips seeded with regenerative cells are effective promoters of peripheral nerve repair
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2017 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 11, no 3, p. 812-821Article in journal (Refereed) Published
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.

Keywords
biomaterial, muscle, nerve injury, regeneration, Schwann cells, stem cells
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-106901 (URN)10.1002/term.1980 (DOI)000398046600021 ()25556632 (PubMedID)
Available from: 2015-08-12 Created: 2015-08-12 Last updated: 2018-06-07Bibliographically approved
Tremp, M., Schwabedissen, M. M., Kappos, E. A., Engels, P. E., Fischmann, A., Scherberich, A., . . . Kalbermatten, D. F. (2015). The Regeneration Potential After Human and Autologous Stem Cell Transplantation in a Rat Sciatic Nerve Injury Model Can Be Monitored by MRI. Cell Transplantation, 24(2), 203-211
Open this publication in new window or tab >>The Regeneration Potential After Human and Autologous Stem Cell Transplantation in a Rat Sciatic Nerve Injury Model Can Be Monitored by MRI
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2015 (English)In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 24, no 2, p. 203-211Article in journal (Refereed) Published
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.

Keywords
Adult stem cells, Tissue engineering, Nerve regeneration, Transplantation, Heterologous
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-102479 (URN)10.3727/096368913X676934 (DOI)000351251400006 ()24380629 (PubMedID)
Available from: 2015-05-19 Created: 2015-04-26 Last updated: 2018-06-07Bibliographically approved
di Summa, P. G., Kingham, P. J., Campisi, C. C., Raffoul, W. & Kalbermatten, D. F. (2014). Collagen (NeuraGen(®)) nerve conduits and stem cells for peripheral nerve gap repair. Neuroscience Letters, 572, 26-31
Open this publication in new window or tab >>Collagen (NeuraGen(®)) nerve conduits and stem cells for peripheral nerve gap repair
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2014 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 572, p. 26-31Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Peripheral nerve regeneration, FDA-approved collagen conduits, Adipose-derived stem cells, Schwann cell-like differentiation
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-88635 (URN)10.1016/j.neulet.2014.04.029 (DOI)000338397300006 ()24792394 (PubMedID)
Available from: 2014-05-12 Created: 2014-05-12 Last updated: 2018-06-07Bibliographically approved
di Summa, P. G., Kalbermatten, D. F., Raffoul, W., Terenghi, G. & Kingham, P. J. (2013). Extracellular matrix molecules enhance the neurotrophic effect of Schwann cell-like differentiated adipose-derived stem cells and increase cell survival under stress conditions. Tissue Engineering. Part A, 19(3-4), 368-379
Open this publication in new window or tab >>Extracellular matrix molecules enhance the neurotrophic effect of Schwann cell-like differentiated adipose-derived stem cells and increase cell survival under stress conditions
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2013 (English)In: Tissue Engineering. Part A, ISSN 1937-3341, E-ISSN 1937-335X, Vol. 19, no 3-4, p. 368-379Article in journal (Refereed) Published
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.

National Category
Microbiology in the medical area Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-65906 (URN)10.1089/ten.tea.2012.0124 (DOI)000313423700006 ()
Available from: 2013-03-21 Created: 2013-02-13 Last updated: 2018-06-08Bibliographically approved
Engels, P. E., Tremp, M., Kingham, P. J., di Summa, P. G., Largo, R. D., Schaefer, D. J. & Kalbermatten, D. F. (2013). Harvest site influences the growth properties of adipose derived stem cells. Cytotechnology (Dordrecht), 65(3), 437-445
Open this publication in new window or tab >>Harvest site influences the growth properties of adipose derived stem cells
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2013 (English)In: Cytotechnology (Dordrecht), ISSN 0920-9069, E-ISSN 1573-0778, Vol. 65, no 3, p. 437-445Article in journal (Refereed) Published
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.

Keywords
Growth factor, ASC, Proliferation, Stem cell, Tissue engineering
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-68247 (URN)10.1007/s10616-012-9498-2 (DOI)000316220500013 ()
Available from: 2013-04-19 Created: 2013-04-15 Last updated: 2018-06-08Bibliographically approved
Schaakxs, D., Kalbermatten, D. F., Raffoul, W., Wiberg, M. & Kingham, P. J. (2013). Regenerative cell injection in denervated muscle reduces atrophy and enhances recovery following nerve repair. Muscle and Nerve, 47(5), 691-701
Open this publication in new window or tab >>Regenerative cell injection in denervated muscle reduces atrophy and enhances recovery following nerve repair
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2013 (English)In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 47, no 5, p. 691-701Article in journal (Refereed) Published
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.

Keywords
denervation, muscle atrophy, peripheral nerve lesion, Schwann cells, stem cells
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-72702 (URN)10.1002/mus.23662 (DOI)000318234200010 ()
Available from: 2013-06-11 Created: 2013-06-10 Last updated: 2018-06-08Bibliographically approved
di Summa, P. G., Kalbermatten, D. F., Pralong, E., Raffoul, W., Kingham, P. J. & Terenghi, G. (2011). Long-term in vivo regeneration of peripheral nerves through bioengineered nerve grafts. Neuroscience, 181(5), 278-291
Open this publication in new window or tab >>Long-term in vivo regeneration of peripheral nerves through bioengineered nerve grafts
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2011 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 181, no 5, p. 278-291Article in journal (Refereed) Published
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.

Keywords
adipose-derived stem cells; fibrin conduit; nerve repair; Schwann cell
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-42250 (URN)10.1016/j.neuroscience.2011.02.052 (DOI)21371534 (PubMedID)
Available from: 2011-04-06 Created: 2011-04-06 Last updated: 2018-06-08Bibliographically approved
Pettersson, J., McGrath, A., Kalbermatten, D., Novikova, L., Wiberg, M., Kingham, P. & Novikov, L. (2011). Muscle recovery after repair of short and long peripheral nerve gaps using fibrin conduits. Neuroscience Letters, 500(1), 41-46
Open this publication in new window or tab >>Muscle recovery after repair of short and long peripheral nerve gaps using fibrin conduits
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2011 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 500, no 1, p. 41-46Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Amsterdam: , 2011
Keywords
autograft; biosynthetic conduit; muscle fiber; nerve injury; regeneration
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-42426 (URN)10.1016/j.neulet.2011.06.002 (DOI)
Available from: 2011-04-07 Created: 2011-04-07 Last updated: 2018-06-08Bibliographically approved
Kalbermatten, D. F., Schaakxs, D., Kingham, P. J. & Wiberg, M. (2011). Neurotrophic activity of human adipose stem cells isolated from deep and superficial layers of abdominal fat. Cell and Tissue Research, 344(2), 251-260
Open this publication in new window or tab >>Neurotrophic activity of human adipose stem cells isolated from deep and superficial layers of abdominal fat
2011 (English)In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 344, no 2, p. 251-260Article in journal (Refereed) Published
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.

Keywords
Growth factor; Nerve; Regeneration; Stem cell; Tissue engineering
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-42254 (URN)10.1007/s00441-011-1142-5 (DOI)21400216 (PubMedID)
Available from: 2011-04-06 Created: 2011-04-06 Last updated: 2018-06-08Bibliographically approved
di Summa, P. G., Kingham, P. J., Raffoul, W., Wiberg, M., Terenghi, G. & Kalbermatten, D. F. (2010). Adipose-derived stem cells enhance peripheral nerve regeneration. Journal of plastic, reconstructive and aesthetic surgery, 63(9), 1544-1552
Open this publication in new window or tab >>Adipose-derived stem cells enhance peripheral nerve regeneration
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2010 (English)In: Journal of plastic, reconstructive and aesthetic surgery, ISSN 1878-0539, Vol. 63, no 9, p. 1544-1552Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2010
Keywords
Adipose-derived stem cells, Peripheral nerve regeneration, Differentiated cells, Sciatic nerve
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:umu:diva-32013 (URN)10.1016/j.bjps.2009.09.012 (DOI)000281513300034 ()19828391 (PubMedID)
Available from: 2010-03-03 Created: 2010-02-26 Last updated: 2018-06-08Bibliographically approved
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