Dose-dependent facilitation of peripheral nerve regeneration by bone marrow–derived mononuclear cells: a randomized controlled study

2012 ◽  
Vol 117 (6) ◽  
pp. 1170-1181 ◽  
Author(s):  
Amol Raheja ◽  
Vaishali Suri ◽  
Ashish Suri ◽  
Chitra Sarkar ◽  
Arti Srivastava ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Mononuclear Cells ◽  
Peripheral Nerve Regeneration ◽  
Control Group ◽  
High Dose ◽  
Myelin Thickness ◽  
Dose Dependent

Object Bone marrow–derived stem cells enhance the rate of regeneration of neuronal cells leading to clinical improvement in nerve injury, spinal cord injury, and brain infarction. Recent experiments in the local application of bone marrow–derived mononuclear cells (BM-MNCs) in models of sciatic nerve transection in rats have suggested their beneficial role in nerve regeneration, although the effects of variable doses of stem cells on peripheral nerve regeneration have never been specifically evaluated in the literature. In this paper, the authors evaluated the dose-dependent role of BM-MNCs in peripheral nerve regeneration in a model of sciatic nerve transection in rats. Methods The right sciatic nerve of 60 adult female Wistar rats (randomized into 2 test groups and 1 control group, 20 rats in each group) underwent transection under an operating microscope. The cut ends of the nerve were approximated using 2 epineural microsutures. The gap was filled with low-dose (5 million BM-MNCs/100 μl phosphate-buffered saline [PBS]) rat BM-MNCs in one group, high-dose (10 million BM-MNCs/100 μl PBS) rat BM-MNCs in another group, and only PBS in the control group, and the approximated nerve ends were sealed using fibrin glue. Histological assessment was performed after 30 days by using semiquantitative and morphometric analyses and was done to assess axonal regeneration, percentage of myelinated fibers, axonal diameter, fiber diameter, and myelin thickness at distal-most sites (10 mm from site of repair), intermediate distal sites (5 mm distal to the repair site), and site of repair. Results The recovery of nerve cell architecture after nerve anastomosis was far better in the high-dose BM-MNC group than in the low-dose BM-MNC and control groups, and it was most evident (p < 0.02 in the majority of the parameters [3 of 4]) at the distal-most site. Overall, the improvement in myelin thickness was most significant with incremental dosage of BM-MNCs, and was evident at the repair, intermediate distal, and distal-most sites (p = 0.001). Conclusions This study emphasizes the role of BM-MNCs, which can be isolated easily from bone marrow aspirates, in peripheral nerve injury and highlights their dose-dependent facilitation of nerve regeneration.

scholarly journals IL-17F depletion accelerates chitosan conduit guided peripheral nerve regeneration

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Feixiang Chen ◽  
Weihuang Liu ◽  
Qiang Zhang ◽  
Ping Wu ◽  
Ao Xiao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Knockout Mice ◽  
Inflammatory Markers ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Wild Type ◽  
Anti Inflammatory

AbstractPeripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration.

scholarly journals Histopathological analysis of gangliosides use in peripheral nerve regeneration after axonotmesis in rats

2008 ◽  
Vol 23 (4) ◽  
pp. 364-371 ◽  
Author(s):  
Camila Maria Beder Ribeiro ◽  
Belmiro Cavalcanti do Egito Vasconcelos ◽  
Joaquim Celestino da Silva Neto ◽  
Valdemiro Amaro da Silva Júnior ◽  
Nancy Gurgel Figueiredo
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Peripheral Nerve Regeneration ◽  
Cell Activity ◽  
Control Group ◽  
Histopathological Analysis ◽  
Male Wistar Rats ◽  
The Right

PURPOSE: To analyze the action of gangliosides in peripheral nerve regeneration in the sciatic nerve of the rat. METHODS: The sample was composed of 96 male Wistar rats. The animals were anaesthetized and, after identification of the anaesthesic plane, an incision was made in the posterior region of the thigh, followed by skin and muscle divulsion. The right sciatic nerve was isolated and compressed for 2 minutes. Continuous suture of the skin was performed. The animals were randomly divided into two groups: the experimental group (EG), which received subcutaneous injection of gangliosides, and the control group (CG), which received saline solution (0.9%) to mimic the effects of drug administration. RESULTS: No differences were observed between the experimental and control groups evaluated on the eighth day of observation. At 15 and 30 days the EG showed an decrease in Schwann cell activity and an apparent improvement in fibre organization; at 60 days, there was a slight presence of Schwann cells in the endoneural space and the fibres were organized, indicating nerve regeneration. At 15 and 30 days, the level of cell reaction in the CG had diminished, but there were many cells with cytoplasm in activity and in mitosis; at 60 days, hyperplastic Schwann cells and mitotic activity were again observed, as well as nerve regeneration, but to a lesser extent than in the EG. CONCLUSION: The administration of exogenous gangliosides seems to improve nerve regeneration.

Trophic activity derived from bone marrow mononuclear cells increases peripheral nerve regeneration by acting on both neuronal and glial cell populations

Neuroscience ◽  
2009 ◽  
Vol 159 (2) ◽  
pp. 540-549 ◽  
Author(s):  
V.T. Ribeiro-Resende ◽  
P.M. Pimentel-Coelho ◽  
L.A. Mesentier-Louro ◽  
R.M.B. Mendez ◽  
J.P.C. Mello-Silva ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Glial Cell ◽  
Mononuclear Cells ◽  
Peripheral Nerve Regeneration ◽  
Cell Populations ◽  
Bone Marrow Mononuclear Cells ◽  
Trophic Activity

Effect of Arecoline on Regeneration of Injured Peripheral Nerves

2013 ◽  
Vol 41 (04) ◽  
pp. 865-885 ◽  
Author(s):  
Sheng-Chi Lee ◽  
Chin-Chuan Tsai ◽  
Chun-Hsu Yao ◽  
Yuan-Man Hsu ◽  
Yueh-Sheng Chen ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerve Regeneration ◽  
In Vitro Study ◽  
Control Group ◽  
Neural Cells ◽  
In Vivo Evaluation

The present study provides in vitro and in vivo evaluation of arecoline on peripheral nerve regeneration. In the in vitro study, we found that arecoline at 50 μg/ml could significantly promote the survival and outgrowth of cultured Schwann cells as compared to the controls treated with culture medium only. In the in vivo study, we evaluated peripheral nerve regeneration across a 10-mm gap in the sciatic nerve of the rat, using a silicone rubber nerve chamber filled with the arecoline solution. In the control group, the chambers were filled with normal saline only. At the end of the fourth week, morphometric data revealed that the arecoline-treated group at 5 μg/ml significantly increased the number and the density of myelinated axons as compared to the controls. Immunohistochemical staining in the arecoline-treated animals at 5 μg/ml also showed their neural cells in the L4 and L5 dorsal root ganglia ipsilateral to the injury were strongly retrograde-labeled with fluorogold and lamina I–II regions in the dorsal horn ipsilateral to the injury were significantly calcitonin gene-related peptide-immunolabeled compared with the controls. In addition, we found that the number of macrophages recruited in the distal sciatic nerve was increased as the concentration of arecoline was increased. Electrophysiological measurements showed the arecoline-treated groups at 5 and 50 μg/ml had a relatively larger nerve conductive velocity of the evoked muscle action potentials compared to the controls. These results indicate that arecoline could stimulate local inflammatory conditions, improving the recovery of a severe peripheral nerve injury.

The effect of exercise on mobilization of hematopoietic progenitor cells involved in the repair of sciatic nerve crush injury [RETRACTED]

2013 ◽  
Vol 118 (3) ◽  
pp. 594-605 ◽  
Author(s):  
Fu-Chou Cheng ◽  
Meei-Ling Sheu ◽  
Hong-Lin Su ◽  
Ying-Ju Chen ◽  
Chun-Jung Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sciatic Nerve ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Progenitor Cells ◽  
Treadmill Exercise ◽  
Peripheral Nerve Regeneration ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor

Object Mobilization of hematopoietic progenitor cells (HPCs) from bone marrow involved in the process of peripheral nerve regeneration occurs mostly through deposits of CD34+ cells. Treadmill exercise, with either differing intensity or duration, has been shown to increase axon regeneration and sprouting, but the effect of mobilization of HPCs on peripheral nerve regeneration due to treadmill exercise has not yet been elucidated. Methods Peripheral nerve injury was induced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were categorized into 2 groups: those with and without treadmill exercise (20 m/min for 60 minutes per day for 7 days). Cytospin and flow cytometry were used to determine bone marrow progenitor cell density and distribution. Neurobehavioral analysis, electrophysiological study, and regeneration marker expression were investigated at 1 and 3 weeks after exercise. The accumulation of HPCs, immune cells, and angiogenesis factors in injured nerves was determined. A separate chimeric mice study was conducted to assess CD34+ cell distribution according to treadmill exercise group. Results Treadmill exercise significantly promoted nerve regeneration. Increased Schwann cell proliferation, increased neurofilament expression, and decreased Schwann cell apoptosis were observed 7 days after treadmill exercise. Elevated expression of S100 and Luxol fast blue, as well as decreased numbers of vacuoles, were identified in the crushed nerve 3 weeks after treadmill exercise. Significantly increased numbers of mononuclear cells, particularly CD34+ cells, were induced in bone marrow after treadmill exercise. The deposition of CD34+ cells was abolished by bone marrow irradiation. In addition, deposits of CD34+ cells in crushed nerves paralleled the elevated expressions of von Willebrand factor, isolectin B4, and vascular endothelial growth factor. Conclusions Bone marrow HPCs, especially CD34+ cells, were able to be mobilized by low-intensity treadmill exercise, and this effect paralleled the significant expression of angiogenesis factors. Treadmill exercise stimulation of HPC mobilization during peripheral nerve regeneration could be used as a therapy in human beings.

Peripheral nerve regeneration by transplantation of bone marrow stromal cell—derived Schwann cells in adult rats

2004 ◽  
Vol 101 (5) ◽  
pp. 806-812 ◽  
Author(s):  
Toshiro Mimura ◽  
Mari Dezawa ◽  
Hiroshi Kanno ◽  
Hajime Sawada ◽  
Isao Yamamoto
Keyword(s):  
Bone Marrow ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Peripheral Nerve Regeneration ◽  
Adult Rats ◽  
Content Type ◽  
Alternative Method ◽  
Fine Print

Object. Bone marrow stromal cells (BMSCs) can be induced to form Schwann cells by sequentially treating the cells with β-mercaptoethanol and retinoic acid, followed by forskolin and neurotrophic factors including heregulin. In this study the authors made artificial grafts filled with BMSC-derived Schwann cells (BMSC-DSCs) and transplanted them into the transected sciatic nerve in adult rats to evaluate the potential of BMSCs as a novel alternative method of peripheral nerve regeneration. Methods. The BMSC-DSCs were suspended in Matrigel and transferred into hollow fibers (12 mm in length), which were transplanted into the transected sciatic nerve in adult Wistar rats. Six months after cell transplantation, electrophysiological evaluation and walking track analysis were performed. Results of these studies showed significant improvement in motor nerve conduction velocity and sciatic nerve functional index in the BMSC-DSC—transplanted group compared with the control group (Matrigel graft only). Immunohistochemical study data demonstrated that transplanted BMSCs labeled with retrovirus green fluorescent protein were positive for P0 and myelin-associated glycoprotein and had reconstructed nodes of Ranvier and remyelinated regenerated nerve axons. The number of regenerated axons in the axial section of the central portion of the graft was significantly greater in the transplanted group. Although BMSCs can differentiate into several types of cells, tumor formation did not occur 6 months after engraftment. Conclusions. Results in this study indicate that BMSC-DSCs have great potential to promote regeneration of peripheral nerves. The artificial graft made with BMSC-DSCs represents an alternative method for the difficult reconstruction of a long distance gap in a peripheral nerve.

The Effects of Electroacupuncture on Peripheral Nerve Regeneration in Rats

2003 ◽  
Vol 21 (1-2) ◽  
pp. 9-17 ◽  
Author(s):  
Motohiro Inoue ◽  
Tatsuya Hojo ◽  
Tadashi Yano ◽  
Yasukazu Katsumi
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerve Regeneration ◽  
Weight Ratio ◽  
Control Group ◽  
Cathode Electrode ◽  
Anode Electrode ◽  
Group A ◽  
And Control

This study was designed to examine the effects of electroacupuncture with direct current (DC) on peripheral nerve regeneration. The left sciatic nerve of 55 7-month-old rats was crushed at the thigh. They were ramdomly allocated to four groups: distal cathode DC group (n=15), distal anode DC group (n=14), sham operated group (n=13), and control group (n=13). In the distal cathode DC group, a cathode electrode was connected to an insulated acupuncture needle inserted at 1 cm distal to the injured site, while an anode electrode was connected to a needle inserted at 1 cm proximal to the lesion. In the distal anode DC group, the anode and the cathode electrode were connected to the needle at 1cm distal and proximal to the lesion respectively. In the sham operated group, no electrical stimulation was given to the insulated needle inserted at the same site, and in the control group, no treatment was given. Regeneration of the sciatic nerve was evaluated by the number of evoked EMGs recorded at 12 sites in the plantar region, by their latency, and by the weight ratio of the tibialis anterior at four weeks after the crush injury. Regeneration of the peripheral nerve was faster and more accelerated in the distal cathode DC group than in the other groups, while in the distal anode DC group the regeneration was delayed. This result suggested electroacupuncture with cathode distal orientation might be a useful treatment having the advantage of enabling deeper insertion with minimal tissue damage.

scholarly journals Effect of Frankincense Extract on Nerve Recovery in the Rat Sciatic Nerve Damage Model

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaowen Jiang ◽  
Jun Ma ◽  
Qingwei Wei ◽  
Xinxin Feng ◽  
Lu Qiao ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Dose Group ◽  
High Dose Group ◽  
Histological Evaluation ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Significant Difference

This study investigated the effect of frankincense extract on peripheral nerve regeneration in a crush injury rat model. Forty-eight Sprague-Dawley rats were randomly divided into four groups: control and frankincense extract low-, medium-, and high-dose groups. At days 7, 14, 21, and 28 following the surgery, nerve regeneration and functional recovery were evaluated using the sciatic functional index (SFI), expression of GAP-43, and the proliferation of Schwann cells (SCs) in vivo and in vitro. At day 7, the SFI in the frankincense extract high-dose group was significantly improved compared with the control group. After day 14, SFI was significantly improved in the medium- and high-dose groups. There was no significant difference in GAP-43 expression among the groups at day 7. However, after day 14, expression of GAP-43 in the high-dose group was higher than that in the control group. Histological evaluation showed that the injured nerve of frankincense extract high-dose group recovered better than the other groups 28 days after surgery. Further, S100 immunohistochemical staining, MTT colorimetry, and flow cytometry assays all showed that frankincense extract could promote the proliferation of SCs. In conclusion, frankincense extract is able to promote sciatic nerve regeneration and improve the function of a crushed sciatic nerve. This study provides a new direction for the repair of peripheral nerve injury.

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