Cerebrospinal fluid from Alzheimer\u2019s disease patients as an optimal formulation for therapeutic application of mesenchymal stem cells in Alzheimer\u2019s disease

Jeongmin Lee,Jong Hwa Kim,Jong Wook Chang,Duk L. Na,Hyemin Jang,Jung Won Hwang,Jang Hoon Kim,Soo Jin Kwon,Na Kyung Lee

doi:10.1038/s41598-018-37252-9

Jeongmin Lee, Jong Hwa Kim + Show 7 more

Open Access

https://doi.org/10.1038/s41598-018-37252-9

Copy DOI

Journal: Scientific Reports	Publication Date: Jan 24, 2019
Citations: 14	License type: open-access

Affiliation: Sungkyunkwan University, Samsung Medical Center

Abstract

Mesenchymal stem cells (MSCs) have emerged as one of the promising treatment options for Alzheimer’s disease (AD). Although many studies have investigated on the efficacy of MSCs in AD, how MSCs actually change following exposure to the AD environment has not been studied extensively. In this study, we investigated on the potential of AD patient-cerebrospinal fluid (CSF) samples to be used as a formulation of MSCs and its application in AD therapeutics. When Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) were stored in the CSF of AD patients, the stemness of WJ-MSCs was preserved. Furthermore, several genes were upregulated following storage in AD CSF. This signified the therapeutic potential of CSF formulation for AD therapy. Overall, these findings suggest that CSF from AD patients can be an optimal source for MSC formulation.

Highlights

Found in the stroma of bone marrow[1], mesenchymal stem cells (MSCs) are multipotent progenitor cells which have recently been studied extensively due to their immune modulatory and trophic functions[2]
We investigated whether the viability and stemness of WJ-Mesenchymal stem cells (MSCs) were compromised following exposure to cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients or normal controls
These studies indicated that a therapeutic interaction existed between the paracrine factors secreted by the MSCs and the endogenous progenitors present in the brain

Summary

Introduction

Found in the stroma of bone marrow[1], mesenchymal stem cells (MSCs) are multipotent progenitor cells which have recently been studied extensively due to their immune modulatory and trophic functions[2]. A growing body of clinical studies is underway to investigate the safety and efficacy of MSCs when administered to AD patients[14,15,16]. Efficacy, and route of administration have been addressed, the clinical grade production of MSCs as a drug product has not been investigated in-depth[20]. Current formulations for MSCs often include supplements to promote the survival of MSCs. some supplements may not exist in the body, possibilities of undesirable interactions between excipients and internal factors of recipients following injection cannot be ruled out. When producing clinical grade MSCs, cerebrospinal fluid (CSF) samples from AD patients may have the potential to be applied as an optimal formulation of MSCs for the following reasons. Correspondence and requests for materials should be addressed to J.W.C

Methods

Results

Conclusion