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Mesenchymal stromal cells --- immunology

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Medicine --- Immunology --- mesenchymal stem cells --- mesenchymal stromal cells --- immunomodulation --- regeneration --- mechanism of action --- safety --- efficacy --- potency analysis

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Somatic stem cells reside in definite compartments, known as “niches”, within developed organs and tissues, being able to renew themselves, differentiate and ensure tissue maintenance and repair. In contrast with the original dogmatic distinction between renewing and non-renewing tissues, somatic stem cells have been found in almost every human organ, including brain and heart. Mesenchymal stem cells (MSCs) are multipotent cells residing in the connective stroma of adult tissues and organs, endowed with outstanding plasticity and trophic features. Strictly-defined MSCs have been originally described as fibroblastoid cells in the bone marrow stroma, able to give rise to differentiated bone cells. Thereafter, additional tissue sources, including adipose tissue, skin, muscle, among others, have been exploited for isolating cell populations that share MSC-like biological features. MSCs are able to differentiate along multiple mesodermal lineages and are believed to represent the key somatic stem cell within the skeletogenic niche, being conceptually able to produce any tissue included within a mature skeletal segment (bone, cartilage, blood vessels, adipose tissue, and supporting connective stroma). Despite this high plasticity, the claim that MSCs could be capable of transdifferentiation along non-mesodermal lineages, including neurons, has been strongly argued. No clear scientific clue has indeed proved the possibility to achieve a functional non-mesordermal phenotype upon MSCs in vitro induction or in vivo inoculation. Adult osteogenic and neurogenic niches display wide differences: embryo origin, microenvironment, progenitors’ lifespan, lineages of supporting cells. Although similar pathways may be involved, it is hard to believe that the osteogenic and neurogenic lineages can share functional features. Beyond embryo stage, neurogenesis persists throughout postnatal life in the subventricular zone (SVZ) of the forebrain lateral ventricles and in the subgranular zone of the hippocampus of adult brain. Here the principal reservoirs of adult neural stem cells reside in specific niches and generate neurons and glial cells to sustain the turnover of selected brain compartments. Studying these reservoirs is useful to gather information on the specialized cellular microenvironments and molecular signals that are needed to maintain neural stem cells in vivo, regulating the fine equilibrium between proliferation and differentiation, acting on the switch between symmetrical and asymmetrical cell division. Based on this contemporary background, this Research Topic wish to provide an in-depth revision of the state of the art on relevant scientific milestones addressing the differences and possible interconnections and overlaps, between the osteogenic and the neurogenic niche, clarifying the questioned issue of neuronal transdifferentiation of somatic stem cells.

Neuroscience. --- Neuropeptide Y --- Stem Cell Niche --- Mesenchymal Stromal Cells --- Neural Stem Cells --- Regenerative Medicine --- Wnt/beta-catenin signaling --- Bone Marrow --- Neural Crest --- RUNX2

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Background: Kidney transplantation remains the first-choice treatment for end-stage renal disease (ESRD). The demand for kidney transplants is rising annually and the shortage of organs is becoming more severe. This has led to the criteria for donors being expanded to include donation after circulatory death (DCD) and poorer quality (Senior age, potential medical conditions, etc.) donations after brain death (DBD). They tend to have poorer short- and long-term outcomes. A way needs to be found to mitigate the effects of ischemia-reperfusion injury on the graft in this type of donor. Our previous studies have identified mesenchymal stromal cell (MSC) pre-exposure as a potential treatment, and we hope to further validate its effects in rat DBD and DCD models.
Objectif: We aimed to evaluate the effects of MSC pre-exposure on different types of renal grafts through the quantification of kidney injury molecule 1 (KIM-1), a highly sensitive and highly specific biomarker of kidney injury.
Methods: Two rat models (DBD and DCD) were established to obtain kidneys in different transplant situations. Two sets of serum samples, one set of urine samples and two kidneys from each rat were obtained during the procedure i: a clinical assessment of renal function (SCr, BUN) was performed. ii: Microarchitecture of grafts assessed by (immuno) histochemistry (PAS staining and KIM-1 IHC). iii: Expression of HAVCR-1 (KIM-1 gene) in tissues was assessed by q-PCR.
Conclusions: Our preliminary findings suggest that brain death and cold ischemia exacerbate the extent of kidney injury in rats, and that MSC pre-exposure may have different effects on DCD and DBD. For DBD kidneys, MSC pre-exposure may be a potential means of reducing injury. Further research is required to confirm the results. Background: La transplantation rénale reste le traitement de premier choix de l'insuffisance rénale terminale (IRT). La demande de transplantations rénales augmente chaque année et la pénurie d'organes s'aggrave. Les critères de sélection des donneurs ont donc été élargis pour inclure les dons après la mort circulatoire (DCD) et les dons après la mort cérébrale (DBD) de moins bonne qualité (âge avancé, conditions médicales potentielles, etc.). Ces derniers ont tendance à avoir de moins bons résultats à court et à long terme. Il faut trouver un moyen d'atténuer les effets des lésions d'ischémie-reperfusion sur le greffon chez ce type de donneur. Nos études précédentes ont identifié la pré-exposition aux cellules stromales mésenchymateuses (CSM) comme un traitement potentiel, et nous espérons valider davantage ses effets dans des modèles de DBD et de DCD chez le rat.
Objectif: Nous avons voulu évaluer les effets de la pré-exposition des CSM sur différents types de greffons rénaux par la quantification de kidney injury molecule 1 (KIM-1), un biomarqueur très sensible et très spécifique de lésion rénale.
Méthodes: Deux modèles de rat (DBD et DCD) ont été établis pour obtenir des reins dans différentes situations de transplantation. Deux séries d'échantillons de sérum, une série d'échantillons d'urine et deux reins de chaque rat ont été prélevés au cours de la procédure : i : une évaluation clinique de la fonction rénale (SCr, BUN) a été réalisée. ii : la microarchitecture des greffons a été évaluée par (immuno) histochimie (coloration PAS et KIM-1 IHC). iii : L'expression du HAVCR-1 (gène KIM-1) dans les tissus a été évaluée par q-PCR.
Conclusions: Nos résultats préliminaires suggèrent que la mort cérébrale et l'ischémie froide exacerbent l'étendue des lésions rénales chez les rats, et que la pré-exposition aux CSM peut avoir des effets différents selon le type de doneur. Pour les reins de DBD, la pré-exposition aux CSM peut être un moyen potentiel de réduire les lésions. Des recherches supplémentaires sont nécessaires pour confirmer ces résultats.

Nephrology --- Mesenchymal Stromal Cells --- Kidney Injury Molecule-1 --- Kidney transplantation --- Ischemia-reperfusion injury --- Ischemic preconditioning --- Sciences de la santé humaine > Urologie & néphrologie

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Multipotent Stem Cells --- MSCs --- Adult Stem Cells --- cancer-associated MSCs --- Mesenchymal Stromal Cells --- Multipotent cell differentiation --- Bone Marrow Transplantation --- nestin --- congenital heart disease --- in vivo MSC