title: Effects of Multiple Injection of Bone Marrow Mononuclear Cells on Spinal Cord Injury of Rats.
abstract: The effects of multiple injection of bone marrow mononuclear cells (BMNCs) on spinal cord injury (SCI) were compared with those of single injection in rats. BMNCs separated by density-gradient centrifugation from a bone marrow perfusate were injected three times (once weekly) through the cerebrospinal fluid (CSF) via the fourth ventricle, and the locomotor improvement and tissue recovery, including axonal regeneration, were compared with those of single injection. While the single-injection group showed a steep elevation of the Basso-Beattie-Bresnahan (BBB) score 1 week after transplantation, the multiple-injection group maintained a similar steep elevation for 2 weeks after transplantation, and the BBB scores of the multiple-injection group remained thereafter at a level approximately 2-3 points higher than those of the single-injection group until the end of the experiment. There were significant differences between the single- and multiple-injection groups at 3, 4, and 8 weeks after transplantation. The difference in BBB scores at 8 weeks after transplantation suggested that there was a marked difference in the quality of locomotor behaviors between the single-and multiple-injection groups at this stage. An extensive outgrowth of regenerating axons through the astrocyte-devoid areas and a marked reduction of cavity formation were found in both the single- and multiple-injection groups. There were, however, no significant differences in the density of regenerating axons or volumes of cavities between the single- and multiple-injection groups. These results showed that although tissue recoveries were similar between single and multiple injection, the multiple injection of BMNCs was more beneficial for locomotor improvement than single injection for the treatment of SCI. Considering the technically simple and low-cost procedures for the preparation and injection of BMNCs, multiple injection of BMNCs by lumbar puncture has an advantage over single injection on clinical application.
authors.affiliation: 1 The Central Biomedical Laboratory, Aino University School of Health Science , Ibaraki City, Osaka, Japan .
authors.forename: Kenji
authors.initials: K
authors.lastname: Kanekiyo
authors.affiliation: 1 The Central Biomedical Laboratory, Aino University School of Health Science , Ibaraki City, Osaka, Japan .
authors.forename: Norihiko
authors.initials: N
authors.lastname: Nakano
authors.affiliation: 1 The Central Biomedical Laboratory, Aino University School of Health Science , Ibaraki City, Osaka, Japan .
authors.forename: Tamami
authors.initials: T
authors.lastname: Homma
authors.affiliation: 2 Department of Physical Therapy, Aino University School of Health Science , Ibaraki City, Osaka, Japan .
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: 2 Department of Physical Therapy, Aino University School of Health Science , Ibaraki City, Osaka, Japan .
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tamachi
authors.affiliation: 3 Department of Plastic and Reconstructive Surgery, Tazuke Medical Research Institute , Kitano Hospital, Osaka City, Osaka, Japan .
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: 4 Translational Research Informatics Center , Foundation for Biomedical Research and Innovation, Kobe City, Hyogo Prefecture, Japan .
authors.forename: Masanori
authors.initials: M
authors.lastname: Fukushima
authors.affiliation: 5 Emergency and Clinical Care Center, Kansai Medical University , Hirakata City, Osaka, Japan .
authors.forename: Fukuki
authors.initials: F
authors.lastname: Saito
authors.affiliation: 1 The Central Biomedical Laboratory, Aino University School of Health Science , Ibaraki City, Osaka, Japan .
authors.forename: Chizuka
authors.initials: C
authors.lastname: Ide
mesh_terms: D000818:Animals; D005260:Female; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009416:Nerve Regeneration; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000473:pathology*
keywords: axonal regeneration; bone marrow mononuclear cell; bone marrow stromal cells; locomotor improvement; multiple-injection; spinal cord injury