title: Dose-dependent facilitation of peripheral nerve regeneration by bone marrow-derived mononuclear cells: a randomized controlled study: laboratory investigation.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurosurgery and Gamma Knife, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Amol
authors.initials: A
authors.lastname: Raheja
authors.forename: Vaishali
authors.initials: V
authors.lastname: Suri
authors.forename: Ashish
authors.initials: A
authors.lastname: Suri
authors.forename: Chitra
authors.initials: C
authors.lastname: Sarkar
authors.forename: Arti
authors.initials: A
authors.lastname: Srivastava
authors.forename: Sujata
authors.initials: S
authors.lastname: Mohanty
authors.forename: Krishan G
authors.initials: KG
authors.lastname: Jain
authors.forename: Meher C
authors.initials: MC
authors.lastname: Sharma
authors.forename: Hruda N
authors.initials: HN
authors.lastname: Mallick
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Yadav
authors.forename: Mani
authors.initials: M
authors.lastname: Kalaivani
authors.forename: Ravindra M
authors.initials: RM
authors.lastname: Pandey
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D009000:Monocytes / Q000637:transplantation*; D009413:Nerve Fibers, Myelinated; D009416:Nerve Regeneration; D010525:Peripheral Nerves / Q000503:physiopathology / Q000601:surgery; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*