title: Human cerebrospinal fluid regulates proliferation and migration of stem cells through insulin-like growth factor-1.
abstract: Mesenchymal stem cells (MSCs) and neural progenitor cells (NPCs) have been regarded for their clinical therapeutic potential for central nervous system (CNS) pathologies. Their potential utility is a result of their intrinsic ability to repair damaged tissues, deliver therapeutic proteins, and migrate to sites of pathology within the brain. However, it remains unclear whether the CNS promotes any changes in these potential therapeutic cells, which would be critical to understand before clinical application. A major component of the CNS is cerebrospinal fluid (CSF). Therefore, the aim of this study was to evaluate the influence that human CSF has on the function of human adipose-derived MSCs (hAMSCs) and human fetal-derived NPCs (hfNPCs) in regard to cell proliferation, survival, and migration. This study demonstrated that human noncancerous CSF promoted proliferation and inhibited apoptosis of hAMSCs and hfNPCs. Preculturing these stem cells in human CSF also increased their migratory speed and distance traveled. Furthermore, insulin-like growth factor-1 (IGF-1) in human CSF enhanced the migration capacity and increased the expression of C-X-C chemokine receptor type 4 (CXCR4) in both stem cell types. These current findings highlight a simple and natural way in which human CSF can enhance the proliferation, migration, and viability of human exogenous primary hAMSCs and hfNPCs. This study may provide insight into improving the clinical efficacy of stem cells for the treatment of CNS pathologies.
authors.affiliation: 1 Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Mingxin
authors.initials: M
authors.lastname: Zhu
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.forename: Sean
authors.initials: S
authors.lastname: Dangelmajer
authors.forename: Hugo
authors.initials: H
authors.lastname: Guerrero-Cázares
authors.forename: Kaisorn L
authors.initials: KL
authors.lastname: Chaichana
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Smith
authors.forename: Andre
authors.initials: A
authors.lastname: Levchenko
authors.forename: Ting
authors.initials: T
authors.lastname: Lei
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quiñones-Hinojosa
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000096:biosynthesis
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D007334:Insulin-Like Growth Factor I