Skip to main content
Top
Published in: Journal of Orthopaedic Science 1/2013

01-01-2013 | Original Article

Uncultured adipose-derived regenerative cells promote peripheral nerve regeneration

Authors: Seigo Suganuma, Kaoru Tada, Katsuhiro Hayashi, Akihiko Takeuchi, Naotoshi Sugimoto, Kazuo Ikeda, Hiroyuki Tsuchiya

Published in: Journal of Orthopaedic Science | Issue 1/2013

Login to get access

Abstract

Background

We examined whether or not peripheral nerves can be regenerated using uncultured adipose-derived regenerative cells (ADRCs). We also searched for humoral factors that might promote the proliferation or migration of Schwann cells.

Methods

Thirty rats were randomly assigned to three groups. A 10 mm sciatic nerve defect was bridged using a silicon tube filled with physiological saline (control group), type I collagen gel (collagen group), and a mixture of ADRCs and type I collagen gel (ADRC group). The regenerated tissues were studied two weeks after surgery.

Results

Continuity of regenerated tissue was observed in all rats in the control group and the ADRC group. In the collagen group, only two rats had a bridge of thin tissue, which was barely visible macroscopically. Protein gene product 9.5 staining confirmed significantly faster regeneration in the ADRC group. The distributions of the PKH-26 positive areas and the S-100 protein positive areas were different, suggesting that the transplanted cells had not differentiated into Schwann cells. In real-time RT-PCR, neuregulin-1 (Neu-1) and vascular endothelial growth factor A (VEGFA) expression were detected in uncultured ADRCs before transplantation. The regenerated tissue in the ADRC group had higher levels of Neu-1 and VEGFA expression than the control group.

Conclusions

ADRCs promote peripheral nerve regeneration. The mechanism does not involve the differentiation of transplanted cells into Schwann cells, but probably involves the secretion of some type of humoral factor such as Neu-1 or VEGFA that promotes the proliferation or migration of Schwann cells.
Literature
1.
go back to reference Millesi H, Meissl G, Berger A. The interfascicular nerve-grafting of the median and ulnar nerves. J Bone Joint Surg Am. 1972;54:727–50.PubMed Millesi H, Meissl G, Berger A. The interfascicular nerve-grafting of the median and ulnar nerves. J Bone Joint Surg Am. 1972;54:727–50.PubMed
2.
go back to reference Battiston B, Geuna S, Ferrero M, Tos P. Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair. Microsurgery. 2005;25:258–67.PubMedCrossRef Battiston B, Geuna S, Ferrero M, Tos P. Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair. Microsurgery. 2005;25:258–67.PubMedCrossRef
3.
go back to reference Cordeiro PG, Seckel BR, Lipton SA, D’Amore PA, Wagner J, Madison R. Acidic fibroblast growth factor enhances peripheral nerve regeneration in vivo. Plast Reconstr Surg. 1989;83:1013–9.PubMedCrossRef Cordeiro PG, Seckel BR, Lipton SA, D’Amore PA, Wagner J, Madison R. Acidic fibroblast growth factor enhances peripheral nerve regeneration in vivo. Plast Reconstr Surg. 1989;83:1013–9.PubMedCrossRef
4.
go back to reference Aebischer P, Salessiotis AN, Winn SR. Basic fibroblast growth factor released from synthetic guidance channels facilitates peripheral nerve regeneration across long nerve gaps. J Neurosci Res. 1989;23:282–9.PubMedCrossRef Aebischer P, Salessiotis AN, Winn SR. Basic fibroblast growth factor released from synthetic guidance channels facilitates peripheral nerve regeneration across long nerve gaps. J Neurosci Res. 1989;23:282–9.PubMedCrossRef
5.
go back to reference Bailey SB, Eichler ME, Villadiego A, Rich KM. The influence of fibronectin and laminin during Schwann cell migration and peripheral nerve regeneration through silicon chambers. J Neurocytol. 1993;22:176–84.PubMedCrossRef Bailey SB, Eichler ME, Villadiego A, Rich KM. The influence of fibronectin and laminin during Schwann cell migration and peripheral nerve regeneration through silicon chambers. J Neurocytol. 1993;22:176–84.PubMedCrossRef
6.
go back to reference Hollowell JP, Villadiego A, Rich KM. Sciatic nerve regeneration across gaps within silicone chambers: long-term effects of NGF and consideration of axonal branching. Exp Neurol. 1990;110:45–51.PubMedCrossRef Hollowell JP, Villadiego A, Rich KM. Sciatic nerve regeneration across gaps within silicone chambers: long-term effects of NGF and consideration of axonal branching. Exp Neurol. 1990;110:45–51.PubMedCrossRef
7.
go back to reference Ikeda K, Oda Y, Nakanishi I. Cultured Schwann cells transplanted between nerve gaps promote nerve regeneration. Neuro Orthopedics. 1991;11:7–16. Ikeda K, Oda Y, Nakanishi I. Cultured Schwann cells transplanted between nerve gaps promote nerve regeneration. Neuro Orthopedics. 1991;11:7–16.
8.
go back to reference Cui L, Jiang J, Wei L, Zhou X, Zhou X, Fraser JL, Snider BJ, Yu SP. Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats. Stem Cells. 2008;26:1356–65.PubMedCrossRef Cui L, Jiang J, Wei L, Zhou X, Zhou X, Fraser JL, Snider BJ, Yu SP. Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats. Stem Cells. 2008;26:1356–65.PubMedCrossRef
9.
go back to reference Kijima Y, Ishikawa M, Sunagawa T, Nakanishi K, Kamei N, Yamada K, Tanaka N, Kawamata S, Asahara T, Ochi M. Regeneration of peripheral nerve after transplantation of CD133+ cells derived from human peripheral blood. J Neurosurg. 2009;110:758–67.PubMedCrossRef Kijima Y, Ishikawa M, Sunagawa T, Nakanishi K, Kamei N, Yamada K, Tanaka N, Kawamata S, Asahara T, Ochi M. Regeneration of peripheral nerve after transplantation of CD133+ cells derived from human peripheral blood. J Neurosurg. 2009;110:758–67.PubMedCrossRef
10.
go back to reference Zhu M, Zhou Z, Chen Y, Schreiber R, Ransom JT, Fraser JK, Hedrick MH, Pinkernell K, Kuo HC. Supplementation of fat grafts with adipose-derived regenerative cells improves long-term graft retention. Ann Plast Surg. 2010;64:222–8.PubMedCrossRef Zhu M, Zhou Z, Chen Y, Schreiber R, Ransom JT, Fraser JK, Hedrick MH, Pinkernell K, Kuo HC. Supplementation of fat grafts with adipose-derived regenerative cells improves long-term graft retention. Ann Plast Surg. 2010;64:222–8.PubMedCrossRef
11.
go back to reference Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7:211–28.PubMedCrossRef Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7:211–28.PubMedCrossRef
12.
go back to reference Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292:154–6.PubMedCrossRef Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292:154–6.PubMedCrossRef
13.
go back to reference Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.PubMedCrossRef Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.PubMedCrossRef
14.
go back to reference Feng Z, Ting J, Alfonso Z, Strem BM, Fraser JK, Rutenberg J, Kuo HC, Pinkernell K. Fresh and cryopreserved, uncultured adipose tissue-derived stem and regenerative cells ameliorate ischemia-reperfusion-induced acute kidney injury. Nephrol Dial Transplant. 2010;25:3874–84.PubMedCrossRef Feng Z, Ting J, Alfonso Z, Strem BM, Fraser JK, Rutenberg J, Kuo HC, Pinkernell K. Fresh and cryopreserved, uncultured adipose tissue-derived stem and regenerative cells ameliorate ischemia-reperfusion-induced acute kidney injury. Nephrol Dial Transplant. 2010;25:3874–84.PubMedCrossRef
15.
go back to reference Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K. Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells. Aesthetic Plast Surg. 2007;32:48–55.PubMedCrossRef Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K. Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells. Aesthetic Plast Surg. 2007;32:48–55.PubMedCrossRef
16.
go back to reference Yoshimura K, Asano Y, Aoi N, Kurita M, Oshima Y, Sato K, Inoue K, Suga H, Eto H, Kato H, Harii K. Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications. Breast J. 2010;16:169–75.PubMedCrossRef Yoshimura K, Asano Y, Aoi N, Kurita M, Oshima Y, Sato K, Inoue K, Suga H, Eto H, Kato H, Harii K. Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications. Breast J. 2010;16:169–75.PubMedCrossRef
17.
go back to reference Alvarez PD, García-Arranz M, Georgiev-Hristov T, Garcia-Olmo D. A new bronchoscopic treatment of tracheomediastinal fistula using autologous adipose-derived stem cells. Thorax. 2008;63:374–6.PubMedCrossRef Alvarez PD, García-Arranz M, Georgiev-Hristov T, Garcia-Olmo D. A new bronchoscopic treatment of tracheomediastinal fistula using autologous adipose-derived stem cells. Thorax. 2008;63:374–6.PubMedCrossRef
18.
go back to reference García-Olmo D, García-Arranz M, Herreros D, Pascual I, Peiro C, Rodríguez-Montes JA. A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005;48:1416–23.PubMedCrossRef García-Olmo D, García-Arranz M, Herreros D, Pascual I, Peiro C, Rodríguez-Montes JA. A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005;48:1416–23.PubMedCrossRef
19.
go back to reference Fang B, Song Y, Lin Q, Zhang Y, Cao Y, Zhao RC, Ma Y. Human adipose tissue-derived mesenchymal stromal cells as salvage therapy for treatment of severe refractory acute graft-vs.-host disease in two children. Pediatr Transplant. 2007;11:814–7.PubMedCrossRef Fang B, Song Y, Lin Q, Zhang Y, Cao Y, Zhao RC, Ma Y. Human adipose tissue-derived mesenchymal stromal cells as salvage therapy for treatment of severe refractory acute graft-vs.-host disease in two children. Pediatr Transplant. 2007;11:814–7.PubMedCrossRef
20.
go back to reference Fang B, Song Y, Zhao RC, Han Q, Lin Q. Using human adipose tissue-derived mesenchymal stem cells as salvage therapy for hepatic graft-versus-host disease resembling acute hepatitis. Transplant Proc. 2007;39:1710–3.PubMedCrossRef Fang B, Song Y, Zhao RC, Han Q, Lin Q. Using human adipose tissue-derived mesenchymal stem cells as salvage therapy for hepatic graft-versus-host disease resembling acute hepatitis. Transplant Proc. 2007;39:1710–3.PubMedCrossRef
21.
go back to reference Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, Fraser JK, Hedrick MH. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med. 2005;54:132–41.PubMedCrossRef Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, Fraser JK, Hedrick MH. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med. 2005;54:132–41.PubMedCrossRef
22.
go back to reference Fraser JK, Zhu M, Wulur I, Alfonso Z. Adipose-derived stem cells. Methods Mol Biol. 2008;449:59–67.PubMed Fraser JK, Zhu M, Wulur I, Alfonso Z. Adipose-derived stem cells. Methods Mol Biol. 2008;449:59–67.PubMed
23.
go back to reference Santiago LY, Clavijo-Alvarez J, Brayfield C, Rubin JP, Marra KG. Delivery of adipose-derived precursor cells for peripheral nerve repair. Cell Transplant. 2009;18:145–58.PubMedCrossRef Santiago LY, Clavijo-Alvarez J, Brayfield C, Rubin JP, Marra KG. Delivery of adipose-derived precursor cells for peripheral nerve repair. Cell Transplant. 2009;18:145–58.PubMedCrossRef
24.
go back to reference di Summa PG, Kingham PJ, Raffoul W, Wiberg M, Terenghi G, Kalbermatten DF. Adipose-derived stem cells enhance peripheral nerve regeneration. J Plast Reconstr Aesthet Surg. 2010;63:1544–52.PubMedCrossRef di Summa PG, Kingham PJ, Raffoul W, Wiberg M, Terenghi G, Kalbermatten DF. Adipose-derived stem cells enhance peripheral nerve regeneration. J Plast Reconstr Aesthet Surg. 2010;63:1544–52.PubMedCrossRef
25.
go back to reference Erba P, Mantovani C, Kalbermatten DF, Pierer G, Terenghi G, Kingham PJ. Regeneration potential and survival of transplanted undifferentiated adipose tissue-derived stem cells in peripheral nerve conduits. J Plast Reconstr Aesthet Surg. 2010;63:e811–7.PubMedCrossRef Erba P, Mantovani C, Kalbermatten DF, Pierer G, Terenghi G, Kingham PJ. Regeneration potential and survival of transplanted undifferentiated adipose tissue-derived stem cells in peripheral nerve conduits. J Plast Reconstr Aesthet Surg. 2010;63:e811–7.PubMedCrossRef
26.
go back to reference Garratt AN, Britsch S, Birchmeier C. Neuregulin, a factor with many functions in the life of a Schwann cell. Bioassays. 2000;22:987–96.CrossRef Garratt AN, Britsch S, Birchmeier C. Neuregulin, a factor with many functions in the life of a Schwann cell. Bioassays. 2000;22:987–96.CrossRef
27.
go back to reference Ogata T, Yamamoto S, Nakamura K, Tanaka S. Signaling axis in Schwann cell proliferation and differentiation. Mol Neurobiol. 2006;33:51–62.PubMedCrossRef Ogata T, Yamamoto S, Nakamura K, Tanaka S. Signaling axis in Schwann cell proliferation and differentiation. Mol Neurobiol. 2006;33:51–62.PubMedCrossRef
28.
29.
go back to reference Sondell M, Lundborg G, Kanje M. Vascular endothelial growth factor stimulates Schwann cell invasion and neovascularization of acellular nerve grafts. Brain Res. 1999;846:219–28.PubMedCrossRef Sondell M, Lundborg G, Kanje M. Vascular endothelial growth factor stimulates Schwann cell invasion and neovascularization of acellular nerve grafts. Brain Res. 1999;846:219–28.PubMedCrossRef
30.
go back to reference Hobson MI, Green CJ, Terenghi G. VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy. J Anat. 2000;197:591–605.PubMedCrossRef Hobson MI, Green CJ, Terenghi G. VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy. J Anat. 2000;197:591–605.PubMedCrossRef
Metadata
Title
Uncultured adipose-derived regenerative cells promote peripheral nerve regeneration
Authors
Seigo Suganuma
Kaoru Tada
Katsuhiro Hayashi
Akihiko Takeuchi
Naotoshi Sugimoto
Kazuo Ikeda
Hiroyuki Tsuchiya
Publication date
01-01-2013
Publisher
Springer Japan
Published in
Journal of Orthopaedic Science / Issue 1/2013
Print ISSN: 0949-2658
Electronic ISSN: 1436-2023
DOI
https://doi.org/10.1007/s00776-012-0306-9

Other articles of this Issue 1/2013

Journal of Orthopaedic Science 1/2013 Go to the issue