TY - JOUR
T1 - Autocrine signals increase ovine mesenchymal stem cells migration through Aquaporin-1 and CXCR4 overexpression
AU - Pelagalli, Alessandra
AU - Nardelli, Anna
AU - Lucarelli, Enrico
AU - Zannetti, Antonella
AU - Brunetti, Arturo
N1 - Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/8
Y1 - 2018/8
N2 - Sheep is a relevant large animal model that is frequently used to test innovative tissue engineering (TE) approaches especially for bone reconstruction. Mesenchymal stem cells (MSCs) are used in TE applications because they represent key component of adult tissue repair. Importantly, MSCs from different species show similar characteristics, which facilitated their application in translational studies using animal models. Nowadays, many researches are focusing on the use of ovine mesenchymal stem cells (oMSCs) in orthopedic preclinical settings for regenerative medicine purposes. Therefore, there is a need to amplify our knowledge on the mechanisms underlying the behaviour of these cells. Recently, several studies have shown that MSC function is largely dependent on factors that MSCs release in the environment, as well as, in conditioned medium (CM). It has been demonstrated that MSCs through autocrine and paracrine signals are able to stimulate proliferation, migration, and differentiation of different type of cells including themselves. In this study, we investigated the effects of the CM produced by oMSCs on oMSCs themselves and we explored the signal pathways involved. We observed that CM caused an enhancement of oMSC migration. Furthermore, we found that CM increased levels of two membrane proteins involved in cell migration, Aquaporin 1 (AQP1), and C-X-C chemokine receptor type 4 (CXCR4), and activated Akt and Erk intracellular signal pathways. In conclusion, taken together our results suggest the high potential of autologous CM as a promising tool to modulate behaviour of MSCs thus improving their use in therapeutically approaches.
AB - Sheep is a relevant large animal model that is frequently used to test innovative tissue engineering (TE) approaches especially for bone reconstruction. Mesenchymal stem cells (MSCs) are used in TE applications because they represent key component of adult tissue repair. Importantly, MSCs from different species show similar characteristics, which facilitated their application in translational studies using animal models. Nowadays, many researches are focusing on the use of ovine mesenchymal stem cells (oMSCs) in orthopedic preclinical settings for regenerative medicine purposes. Therefore, there is a need to amplify our knowledge on the mechanisms underlying the behaviour of these cells. Recently, several studies have shown that MSC function is largely dependent on factors that MSCs release in the environment, as well as, in conditioned medium (CM). It has been demonstrated that MSCs through autocrine and paracrine signals are able to stimulate proliferation, migration, and differentiation of different type of cells including themselves. In this study, we investigated the effects of the CM produced by oMSCs on oMSCs themselves and we explored the signal pathways involved. We observed that CM caused an enhancement of oMSC migration. Furthermore, we found that CM increased levels of two membrane proteins involved in cell migration, Aquaporin 1 (AQP1), and C-X-C chemokine receptor type 4 (CXCR4), and activated Akt and Erk intracellular signal pathways. In conclusion, taken together our results suggest the high potential of autologous CM as a promising tool to modulate behaviour of MSCs thus improving their use in therapeutically approaches.
KW - AQP1
KW - CXCR4
KW - ovine mesenchymal stem cells
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U2 - 10.1002/jcp.26493
DO - 10.1002/jcp.26493
M3 - Article
C2 - 29345324
AN - SCOPUS:85045976063
SN - 0021-9541
VL - 233
SP - 6241
EP - 6249
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 8
ER -