TY - JOUR
T1 - Injured cardiomyocytes promote dental pulp mesenchymal stem cell homing
AU - Di Scipio, F.
AU - Sprio, A. E.
AU - Folino, A.
AU - Carere, M. E.
AU - Salamone, P.
AU - Yang, Z.
AU - Berrone, M.
AU - Prat, M.
AU - Losano, G.
AU - Rastaldo, R.
AU - Berta, G. N.
N1 - Funding Information:
This work was supported by local grant (ex 60%) of the University of Turin and private donations that were generously gifted by “ AMF s.n.c. ”, in the persons of Cinzia Pagliero and Mario Furlanetto, and “ Roda Forge S.p.A. ”, in the person of Donato Manieri. All cytokines utilized in this paper were from ImmunoTools, Friesoythe, Germany, as a Prize to FDS as a Winner of “ImmunoTools Award 2013”. Special thanks to Pasquale Pagliaro and Giancarlo Forte who graciously offered to discuss the manuscript and Susanna Antoniotti and Mauro Papotti who gently provided some antibodies. In addition, we would like to thank Claudio Rullent for his mathematical assistance.
PY - 2014/7
Y1 - 2014/7
N2 - Background The heart is unable to regenerate its tissues after severe injuries. Stem cell therapy appears to be one of the most promising approaches, though preclinical results are hitherto contradictory and clinical trials scanty and/or limited to phase-I. The limited knowledge about stem cell early homing in infarcted cardiac tissues can concur to this scenario. Methods The stem cell migration was assessed in in-vitro and ex-vivo models of heart ischemia, employing a rat dental pulp stem cell line (MUR-1) that shares the same ontogenic progenitors with portions of the heart, expresses markers typical of cardiac/vascular-like progenitors and is able to differentiate into cardiomyocytes in-vitro. Results Here, we demonstrated that the MUR-1 can reach the injured cells/tissue and make contacts with the damaged cardiomyocytes, likely through Connexin 43, N-cadherin and von Willebrand Factor mediated cell-cell interactions, both in in-vitro and ex-vivo models. Furthermore, we found that SDF-1, FGF-2 and HGF, but not VEGF are involved as chemotactic factors in MUR-1 migration, notifying a similarity with neural crest cell behavior during the organogenesis of both the splanchnocranium and the heart. Conclusions Herein we found a similarity between what happens during the heart organogenesis and the early migration and homing of MUR-1 cells in ischemic models. General significance The comprehension of molecular aspects underlying the early phases of stem cell migration and interaction with damaged organ contributes to the future achievement of the coveted stem cell-mediated organ regeneration and function preservation in-vivo.
AB - Background The heart is unable to regenerate its tissues after severe injuries. Stem cell therapy appears to be one of the most promising approaches, though preclinical results are hitherto contradictory and clinical trials scanty and/or limited to phase-I. The limited knowledge about stem cell early homing in infarcted cardiac tissues can concur to this scenario. Methods The stem cell migration was assessed in in-vitro and ex-vivo models of heart ischemia, employing a rat dental pulp stem cell line (MUR-1) that shares the same ontogenic progenitors with portions of the heart, expresses markers typical of cardiac/vascular-like progenitors and is able to differentiate into cardiomyocytes in-vitro. Results Here, we demonstrated that the MUR-1 can reach the injured cells/tissue and make contacts with the damaged cardiomyocytes, likely through Connexin 43, N-cadherin and von Willebrand Factor mediated cell-cell interactions, both in in-vitro and ex-vivo models. Furthermore, we found that SDF-1, FGF-2 and HGF, but not VEGF are involved as chemotactic factors in MUR-1 migration, notifying a similarity with neural crest cell behavior during the organogenesis of both the splanchnocranium and the heart. Conclusions Herein we found a similarity between what happens during the heart organogenesis and the early migration and homing of MUR-1 cells in ischemic models. General significance The comprehension of molecular aspects underlying the early phases of stem cell migration and interaction with damaged organ contributes to the future achievement of the coveted stem cell-mediated organ regeneration and function preservation in-vivo.
KW - Cardiac ischemia
KW - Cell migration
KW - Dental pulp stem cell
KW - Hypoxic cardiomyocyte
UR - http://www.scopus.com/inward/record.url?scp=84899883026&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2014.03.005
DO - 10.1016/j.bbagen.2014.03.005
M3 - Article
SN - 0304-4165
VL - 1840
SP - 2152
EP - 2161
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 7
ER -