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Published on: January 7, 2019
Injured cardiomyocytes promote dental pulp mesenchymal stem cell homing
F Di Scipio1, A E Sprio1, A Folino1
1University of Turin, Department of Clinical and Biological Sciences, 10043 Orbassano, Turin, Italy.
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.
Insights
Researchers studied rat dental pulp stem cells (MUR-1) for heart repair. They found MUR-1 cells migrate to injured heart tissue and interact with damaged cells, similar to early heart development. This aids understanding of stem cell therapy for cardiac regeneration.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Regenerative Medicine
Background:
- The heart's limited capacity for tissue regeneration post-injury necessitates advanced therapeutic strategies.
- Stem cell therapy shows promise but faces challenges due to contradictory preclinical data and limited clinical trials.
- Understanding early stem cell homing in infarcted cardiac tissue is crucial for improving therapeutic outcomes.
Purpose of the Study:
- To investigate the early migration and homing mechanisms of dental pulp stem cells in cardiac ischemia models.
- To identify molecular interactions and chemotactic factors involved in stem cell engagement with damaged heart tissue.
Main Methods:
- Utilized in-vitro and ex-vivo models of heart ischemia.
- Employed a rat dental pulp stem cell line (MUR-1) with cardiac/vascular progenitor markers.
- Assessed stem cell migration, cell-cell interactions, and chemotactic factor involvement.
Main Results:
- MUR-1 cells successfully migrated to and interacted with damaged cardiomyocytes in ischemic heart models.
- Cell-cell interactions were mediated by Connexin 43, N-cadherin, and von Willebrand Factor.
- SDF-1, FGF-2, and HGF were identified as key chemotactic factors for MUR-1 cell migration, mirroring neural crest cell behavior.
Conclusions:
- A similarity was observed between early heart organogenesis and the migration/homing of MUR-1 cells in ischemic models.
- Comprehending the molecular basis of early stem cell migration and interaction is vital for advancing stem cell-mediated cardiac regeneration.
- This research contributes to preserving cardiac function and achieving organ regeneration in vivo.
