Regeneración Cardiaca | BiobancoCelular

Dental pulp-derived stem cell conditioned medium reduces cardiac injury following ischemia-reperfusion.

Yamaguchi S, Shibata R, Yamamoto N, Nishikawa M, Hibi H, TanigawaT, Ueda M, Murohara T, Yamamoto A. Sci Rep.2015 Nov 6;5:16295.

En este estudio, los autores investigan el impacto del medio condicionado derivado de células madre de la pulpa dental en la lesión del miocardio en un modelo de ratón con isquemia-reperfusión (I / R). Los ratones sanos se sometieron a isquemia miocárdica seguida de reperfusión. Posteriormente se inyectó el medio condicionado derivado de células madre de la pulpa dental por vía intravenosa 5 minutos después de la reperfusión. La administración del medio condicionado redujo el tamaño del infarto de miocardio y disminuyó la apoptosis y los niveles de citoquinas inflamatorias en el miocardio después de I / R. Concluyen que el medio condicionado derivado de células madre de la pulpa dental podría ser una opción de tratamiento útil para el infarto agudo de miocardio.

Abstract

Stem cells from human exfoliated deciduous teeth (SHEDs) can regenerate various tissues. We investigated the impact of SHED-conditioned medium (SHED-CM) on myocardial injury in a mouse model of ischemia-reperfusion (I/R). Wild-type (WT) mice were subjected to myocardial ischemia followed by reperfusion. SHED-CM was intravenously injected at 5 min after reperfusion. Administration of SHED-CM reduced myocardial infarct size as well as decreased apoptosis and inflammatory cytokine levels, such as TNF-α, IL-6, and IL-β, in the myocardium following I/R. In cultured cardiac myocytes, SHED-CM significantly suppressed apoptosis under hypoxia/serum-deprivation and reduced LPS-induced expression of pro-inflammatory genes. Furthermore, anti-apoptotic action of SHED-CM was stronger than bone marrow-derived stemcell (BMSC)-CM or adipose-derived stem cell (ADSC)-CM in cardiac myocytes. SHED-CM contains a higher concentration of hepatocyte growth factor (HGF) than BMSC-CM and ADSC-CM, and neutralization of HGF attenuated the inhibitory actions of SHED-CM on apoptosis in cardiac myocytes. Finally, WT mice were intravenously treated with an HGF-depleted SHED-CM, followed by myocardial I/R. HGF depletion significantly attenuated the inhibitory actions of SHED-CM on myocardial infarct size and apoptosis after I/R. SHED-CM protects the heart from acute ischemic injury because it suppresses inflammation and apoptosis. SHED-CM could be a useful treatment option for acute myocardial infarction.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635346/pdf/srep16295.pdf

Injured cardiomyocytes promote dental pulp mesenchymal stem cell homing. Di Scipio F1, Sprio AE1, Folino A1, Carere ME1, Salamone P1, Yang Z1, Berrone M2, Prat M3, Losano G4, Rastaldo R5, Berta GN6. Biochim Biophys Acta. 2014 Jul;1840(7):2152-61.

¨Realizan un estudio con células madre dentales de rata (línea celular MUR-1) y demuestran en modelos ex vivo de isquemia en corazón la capacidad migratoria de las células dentales al área infartada así como su capacidad de diferenciación a cardiomiocitos in vitro¨.

Abstract

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 stemcell 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-1cells 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.

http://www.ncbi.nlm.nih.gov/pubmed/24631652

Transplantation of human dental pulp-derived stem cells protects against heat stroke in mice. Tseng LS, Chen SH, Lin MT, Lin YC. Cell Transplant. 2014 Mar 7. .

¨En este estudio afirman que las células madre de la pulpa dental son prometedoras para el tratamiento del accidente cerebrovascular (Ictus) y lesiones de la médula espinal. Investigan los efectos de las células madre dentales en el tratamiento del daño en múltiples órganos ( incluyendo cerebro e hipotálamo) en ratones que habían sido expuestos a un golpe de calor severo demostrando que tienen un efecto protector muy importante¨.

Abstract

Stem cells from human exfoliated deciduous tooth pulp (SHED) is a promising approach for the treatment of stroke and spinal cord injury. In this study, we investigated the therapeutic effects of SHED for the treatment of multiple organs (including brain or hypothalamus) injury in heat stroke mice. ICR male mice were exposed to whole body heating (WBH; 41.2?, relative humidity 50%~55%, for 1 hour) and then returned to normal room temperature (26?). We observed that intravenous administration of SHED immediately post-WBH exhibited the following therapeutic benefits for recovery after heat stroke: (a) inhibition of WBH-induced neurologic and thermoregulatory deficits; (b) reduction of WBH-induced ischemia, hypoxia, and oxidative damage to brain (or hypothalamus); (c) attenuation of WBH-induced increased plasma levels of systemic inflammatory response molecules such as tumor necrosis factor-alpha and intercellular adhesion molecule-1; (d) improvement of WBH-induced hypothalamo-pituitary-adrenocortical axis activity (as reflected by enhanced plasma levels of both adrenocorticotrophic hormone and corticosterone); and (e) attenuation of WBH-induced multiple organs apoptosis as well as lethality. In conclusion, post-WBH treatment with SHED reduced induction of pro-inflammatory cytokines and oxidative radicals, enhanced plasma induction of both adrenocorticotrophic hormone and corticosterone, and improved lethality in mice heat stroke. The protective effect of SHED may be related to a decreased inflammatory response, a decreased oxidative stress, and an increased hypothalamo-pituitaryadrenocortical axis activity following the WBH injury.

http://www.ncbi.nlm.nih.gov/pubmed/24612725

Human dental pulp stem cells improve left ventricular function, induce angiogenesis, and reduce infarct size in rats with acute myocardial infarction. Gandia C, Armiñan A, García-Verdugo JM, Lledó E, Ruiz A, Miñana MD, Sanchez-Torrijos J, Payá R, Mirabet V, Carbonell-Uberos F, Llop M, Montero JA, Sepúlveda P. Stem Cells. 2008 Mar;26(3):638-45. Epub 2007 Dec 13.

En el estudio, utilizaron un modelo de rata con infarto de miocardio. El trasplante de células madre de la pulpa dental mejoró la función cardiaca tras un infarto de miocardio.

Abstract

Human dental pulp contains precursor cells termed dental pulp stem cells (DPSC) that show self-renewal and multilineage differentiation and also secrete multiple proangiogenic and antiapoptotic factors. To examine whether these cells could have therapeutic potential in the repair of myocardial infarction (MI), DPSC were infected with a retrovirus encoding the green fluorescent protein (GFP) and expanded ex vivo. Seven days after induction of myocardial infarction by coronary artery ligation, 1.5 x 10(6) GFP-DPSC were injected intramyocardially in nude rats. At 4 weeks, cell-treated animals showed an improvement in cardiac function, observed by percentage changes in anterior wall thickening left ventricular fractional area change, in parallel with a reduction in infarct size. No histologic evidence was seen of GFP+ endothelial cells, smooth muscle cells, or cardiac muscle cells within the infarct. However, angiogenesis was increased relative to control-treated animals. Taken together, these data suggest that DPSC could provide a novel alternative cell population for cardiac repair, at least in the setting of acute MI.

http://www.ncbi.nlm.nih.gov/pubmed/18079433