Current Neurovascular Research, 2014, 11, 230-241

Transplantation of Undifferentiated Bone-Marrow Stromal Cells into a Vein Graft Accelerates Sciatic Nerve Regeneration in Streptozotocin Induced Diabetic Rats.

Amin Haghighat1, Rahim Mohammadi2,* and Keyvan Amini3

1Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia Branch, Islamic Azad University, Urmia, Iran
2Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Nazloo Road, Urmia, Iran
3Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon,
Canada

 

ABSTRACT:

Influence of undifferentiated bone marrow stromal cells (BMSCs) combined with vein graft on transected sciatic nerve repair was studied in diabetic rats. A nerve segment, 10 mm, was excised and a vein graft (VG) was used to bridge the gap. 10 microliter undifferentiated BMSCs (2×10(7) cells /mL) were administered into the graft in treatment group (VG/BMSC). Phosphate buffered saline was only administered into the graft in control group. The regenerated nerve fibers were studied in three time points of 4, 8 and 12 weeks after surgery. Evaluation of the repair process was based on behavioral, functional (Walking Track Analysis), electrophysiological, histomorphometrical and immunohistochemical criteria. The behavioral, functional and electrophysiological studies indicated that there was significant recovery in regeneration of axons in VG/BMSC group (P<0.05). Morphometric evaluations showed that the number and diameter of myelinated fibers in VG /BMSC group were significantly higher than those in the control group (P<0.05). This indicates the potential of using undifferentiated BMSCs combined with vein graft in peripheral nerve repair in diabetic rats with no restrictions of donor-site morbidity associated with isolation of Schwann cells. This technique is also cost saving because of decrease in interval from tissue harvest until administration of the cells and simplicity of laboratory techniques in comparison with undifferentiated BMSCs. It may have clinical implications for the surgical management of diabetic patients after nerve transection.

PMID: 24845854

 

SUPPLEMENT:

Regulatory authorities (e.g. the FDA) allow autologous minimally manipulated cell therapy when the procedures do not appreciably change the cells (i.e. differentiation), whereas more manipulative methods, such as differentiation and sorting may require formal approval as a drug before clinical use (1). Undifferentiated BMSCs provide an alternative source of multipotent cells in the form of concentrated nucleated cell populations, many of which may be clinically relevant when compared with differentiated bone marrow (2,3). Thus, choice of undifferentiated BMSCs as more readily accessible and instant source of multipotent cells instead of differentiation might seem more favorable for cell therapy. Our results suggest that some form of trans-differentiation might occur in vivo as the result of local signals from injured Schwann cells and axons. However, the long-term effect of undifferentiated cells remains to be determined and therefore we will continue to study the mechanisms of undifferentiated BMSCs, in the hope of generating clinically useful cells, for the treatment of peripheral nerve injuries.Undifferentiated BMSCs combined with vein graft could provide an injectable, readily accessible and instant source of cells compared to differentiated BMSCs and may have clinical implications for the surgical management of diabetic patients after nerve transection.

References:

1. Nixon AJ, Dahlgren LA, Haupt JL, Yeager AE, Ward DL 2008 Effect of adipose-derived nucleated cell fractions on tendon repair in horses with collagenase-induced tendinitis. Am J Vet Res 69: 928–937
2. Strem BM, Hedrick MH 2005 The growing importance of fat in regenerative medicine. Trends. Biotechnol; 23:64–66
3. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH 2002 Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13: 4279–4295
Acknowledgements: The authors would like to thank Mr. Jaafary, Urmia Pathobiology Center, for the technical help.

Contact:

Rahim Mohammadi,DVM,DVSc
Assistant Professor of Veterinary Surgery,
Department of Surgery and Diagnostic Imaging,
Faculty of Veterinary Medicine,
Urmia University, Urmia, Iran.
Postal Code: 57153-1177
E-mail : r.mohammadivet@gmail.com
r.mohammadi@urmia.ac.ir
Graphical-abstractFig 1. Local transplantation of undifferentiated bone marrow stromal cells into vein graft improve sciatic nerve regeneration in streptozotocin induced diabetic rats.

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