Stem Cell Culture Under Simulated Microgravity

Challenging environment of space causes several pivotal alterations in living systems, especially due to microgravity. The possibility of simulating microgravity by ground-based systems provides research opportunities that may lead to the understanding of

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Stem Cell Culture Under Simulated Microgravity Muge Anil-Inevi, Oyku Sarigil, Melike Kizilkaya, Gulistan Mese, H. Cumhur Tekin, and Engin Ozcivici

Abstract

Challenging environment of space causes several pivotal alterations in living systems, especially due to microgravity. The possibility of simulating microgravity by ground-based systems provides research opportunities that may lead to the understanding of in vitro biological effects of microgravity by eliminating the challenges inherent to spaceflight experiments. Stem cells are one of the most prominent cell types, due to their selfrenewal and differentiation capabilities. Research on stem cells under simulated microgravity has generated many important findings, enlightening the impact of microgravity on molecular and cellular processes of stem cells with varying potencies. Simulation techniques including clinostat, random positioning machine, rotating wall vessel and magnetic levitation-based systems have improved our knowledge on the effects of microgravity on morphology, migration, proliferation and differentiation of stem cells. Clarification of the mechanisms underlying such changes offers exciting potential for M. Anil-Inevi, O. Sarigil, M. Kizilkaya, H. C. Tekin, and E. Ozcivici (*) Department of Bioengineering, Izmir Institute of Technology, Izmir, Turkey e-mail: [email protected] G. Mese Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey

various applications such as identification of putative therapeutic targets to modulate stem cell function and stem cell based regenerative medicine. Keywords

In vitro model · Simulated microgravity · Stem cells

Abbreviations AdhMSC BDNF bFGF BMOL BM cMSC CBSC GDNF GDNF hDPSC HSCs HGF hEpSCs mBMSC MG NG

human adipose-derived mesenchymal stem cell brain derived-neurotrophic factor basic fibroblast growth factor bipotential murine oval liver bone marrow cranial bone derived-mesenchymal stem cell cord blood stem cells glial-cell derived-neurotrophic factor glial cell line-derived neurotrophic factor human dental pulp stem cell hematopoetic stem cells hepatocyte growth factor human epidermal stem cells mouse bone marrow stem cell (simulated) microgravity normal gravity

M. Anil-Inevi et al.

RabBMSC RCCS RWV SSCs TGF-β VEGF

1

rabbit bone marrow stem cell rotating cell culture system rotating wall vessel spermatogonial stem cells transforming growth factor vascular endothelial growth factor

Introduction

Space missions induce many changes in human health and physiology, and among many factors changes in gravitational loading is one of the major contributors to these changes (GarrettBakelman et al. 2019). Mechanical forces, including those governed by gravitational loading, act as regulatory signals that effect morphology and function of tissues (Benjamin and Hillen 2003; Buravkova et al. 2008; Ozcivici et al. 2010a). Therefore, lack of gravity causes several health problems such as bone loss (Vico et al. 2000), muscle atrophy (Fitts et al. 2001), cardiovascular deconditio