title: β-PIX is critical for transplanted mesenchymal stromal cell migration.
abstract: Bone marrow-derived mesenchymal stromal cells (MSCs) have been used successfully as a source of stem cells for treating neurodegenerative diseases. However, for reasons that are not clear, autologous MSC transplants have not yielded successful results in human trials. To test one possible reason, we compared the migratory ability of MSCs from amyotrophic lateral sclerosis (ALS) patients with those of healthy controls. We found that MSCs derived from ALS patients (ALS-MSCs) had a reduced ability to migrate, which may explain why autologous transplantation is not successful. We also found that expression of one of the intracellular factors implicated in migration, β-PIX, was significantly reduced in ALS-MSCs compared with healthy stem cells. Restoration of β-PIX expression by genetic manipulation restored the migratory ability of ALS-MSCs, and inhibition of β-PIX expression with shRNA reduced the migration of healthy MSCs. We suggest that transplantation of allogeneic or genetically modified autologous stem cells might be a more promising strategy for ALS patients than transplantation of autologous stem cells.
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Koh
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Huh
authors.forename: Min Young
authors.initials: MY
authors.lastname: Noh
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Kyung Suk
authors.initials: KS
authors.lastname: Kim
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Lee
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Ko
authors.forename: Goang Won
authors.initials: GW
authors.lastname: Cho
authors.forename: A Rum
authors.initials: AR
authors.lastname: Yoo
authors.forename: Ho-Taek
authors.initials: HT
authors.lastname: Song
authors.forename: Sejin
authors.initials: S
authors.lastname: Hwang
authors.forename: Kwangyeol
authors.initials: K
authors.lastname: Lee
authors.forename: Seungjoo
authors.initials: S
authors.lastname: Haam
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Frank
authors.forename: Jin-Suck
authors.initials: JS
authors.lastname: Suh
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology / Q000628:therapy; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy; D016022:Case-Control Studies; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064067:Rho Guanine Nucleotide Exchange Factors; D014182:Transplantation, Autologous
chemical_list: C576606:ARHGEF7 protein, human; D020662:Guanine Nucleotide Exchange Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D064067:Rho Guanine Nucleotide Exchange Factors