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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.

SUBMITTER: Zhu M

PROVIDER: S-EPMC4291213 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Human cerebrospinal fluid regulates proliferation and migration of stem cells through insulin-like growth factor-1.

Zhu Mingxin M Feng Yun Y Dangelmajer Sean S Guerrero-Cázares Hugo H Chaichana Kaisorn L KL Smith Christopher L CL Levchenko Andre A Lei Ting T Quiñones-Hinojosa Alfredo A

Stem cells and development 20150101 2

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 ...[more]

PMID: 25265906

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Project description:Background: Growing evidence shows that impaired signaling of Insulin-like Growth Factor-1 (IGF-1) is associated with neurodegenerative disorders, such as Parkinson's disease (PD). However, there is still controversy regarding its proinflammatory or neuroprotective function. In an attempt to elucidate the contribution of IGF-1 in PD, we aimed to discover the relation between serum IGF-1 levels in drug-naïve early PD patients and cerebrospinal fluid (CSF) biomarkers as well as microstructural changes in brain white matter. Methods: The association between quartiles of serum IGF-1 levels and CSF biomarkers (?-synuclein, dopamine, amyloid-?1-42, total tau, and phosphorylated tau) was investigated using adjusted regression models in 404 drug-naïve early PD patients with only mild motor manifestations and 188 age- and sex-matched healthy controls (HC) enrolled in the Parkinson's Progression Markers Initiative (PPMI). By using region of interest analysis and connectometry approach, we tracked the white matter microstructural integrity and diffusivity patterns in a subgroup of study participants with available diffusion MRI data to investigate the association between subcomponents of neural pathways with serum IGF-1 levels. Results: PD patients had higher levels of IGF-1 compared to HC, although not statistically significant (mean difference: 3.60, P = 0.44). However, after adjustment for possible confounders and correction for False Discovery Rate (FDR), IGF-1 was negatively correlated with CSF ?-synuclein, total and phosphorylated tau levels only in PD subjects. The imaging analysis proved a significant negative correlation (FDR corrected P-value = 0.013) between continuous levels of serum IGF-1 in patients with PD and the connectivity, but not integrity, in following fibers while controlling for age, sex, body mass index, depressive symptoms, education years, cognitive status and disease duration: middle cerebellar peduncle, cingulum, genu and splenium of the corpus callosum. No significant association was found between brain white matter microstructral measures or CSF markers of healthy controls and levels of IGF-1. Conclusion: Altered connectivity in specific white matter structures, mainly involved in cognitive and motor deterioration, in association with higher serum IGF-1 levels might propose IGF-1 as a potential associate of worse outcome in response to higher burden of ?-synucleinopathy and tauopathy in PD.

Dataset Information

Human cerebrospinal fluid regulates proliferation and migration of stem cells through insulin-like growth factor-1.

Publications

Human cerebrospinal fluid regulates proliferation and migration of stem cells through insulin-like growth factor-1.

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