ResearchPad - concise-reviews https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Effects of mesenchymal stromal cells on regulatory T cells: Current understanding and clinical relevance]]> https://www.researchpad.co/article/elastic_article_8270 Mesenchymal stromal cells (MSCs) promote regulatory T cell numbers and immune suppressive functions through mechanisms involving cell‐cell contact, production of soluble mediators, reprogramming of antigen presenting cells, and release of extracellular vesicles that likely represent important components of MSC therapeutic effects in immune/inflammatory diseases.

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<![CDATA[Advances in generating liver cells from pluripotent stem cells as a tool for modeling liver diseases]]> https://www.researchpad.co/article/elastic_article_6828 Developing robust in vitro models of the liver is essential for studying the pathogenesis of liver diseases, hepatotoxicity testing, and regenerative medicine. Earlier studies were conducted using cell lines derived from hepatomas. Due to the inherent limitations of cell lines, researchers used primary human hepatocytes (PHHs), which are considered a gold standard for in vitro modeling of the liver. However, due to the high cost of PHHs and lack of donors, researchers have sought an alternative source for functional liver cells. Pluripotent stem cells (PSCs) emerged as a viable alternative due to their plasticity and high proliferative capacity. This review gives an overview of the major advances that have been achieved to develop protocols to generate liver cells such as hepatocytes, cholangiocytes, and Küpffer cells from PSCs. We also discuss their application in modeling the pathogenesis of liver diseases such as drug‐induced liver injury, acute liver failure, and hepatic steatosis.

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<![CDATA[Therapeutic vascularization in regenerative medicine]]> https://www.researchpad.co/article/N23469ffc-e2d8-4802-b43a-91fa5ce3006b

Abstract

Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth and vascular tumors (angiomas). Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression. In fact, the therapeutic window of VEGF delivery depends on its amount in the microenvironment around each producing cell rather than on the total dose, since VEGF remains tightly bound to extracellular matrix (ECM). On the other hand, short‐term expression of less than about 4 weeks leads to unstable vessels, which promptly regress following cessation of the angiogenic stimulus. Here, we will briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. Lastly, we will present recent insights into the mechanisms that regulate vessel stabilization and the switch between normal and aberrant vascular growth after VEGF delivery, to identify novel molecular targets that may improve both safety and efficacy of therapeutic angiogenesis.

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<![CDATA[Pulp stem cells derived from human permanent and deciduous teeth: Biological characteristics and therapeutic applications]]> https://www.researchpad.co/article/N6ee53c26-a0be-4b1e-a50c-791f7a79ddae

Abstract

Human pulp stem cells (PSCs) include dental pulp stem cells (DPSCs) isolated from dental pulp tissues of human extracted permanent teeth and stem cells from human exfoliated deciduous teeth (SHED). Depending on their multipotency and sensitivity to local paracrine activity, DPSCs and SHED exert therapeutic applications at multiple levels beyond the scope of the stomatognathic system. This review is specifically concentrated on PSC‐updated biological characteristics and their promising therapeutic applications in (pre)clinical practice. Biologically, distinguished from conventional mesenchymal stem cell markers in vitro, NG2, Gli1, and Celsr1 have been evidenced as PSC markers in vivo. Both perivascular cells and glial cells account for PSC origin. Therapeutically, endodontic regeneration is where PSCs hold the most promises, attributable of PSCs' robust angiogenic, neurogenic, and odontogenic capabilities. More recently, the interplay between cell homing and liberated growth factors from dentin matrix has endowed a novel approach for pulp‐dentin complex regeneration. In addition, PSC transplantation for extraoral tissue repair and regeneration has achieved immense progress, following their multipotential differentiation and paracrine mechanism. Accordingly, PSC banking is undergoing extensively with the intent of advancing tissue engineering, disease remodeling, and (pre)clinical treatments.

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<![CDATA[Preclinical translation of exosomes derived from mesenchymal stem/stromal cells]]> https://www.researchpad.co/article/Nb1caae7d-330c-4b17-9576-b94405fe0fc7

Abstract

Exosomes are nanovesicles secreted by virtually all cells. Exosomes mediate the horizontal transfer of various macromolecules previously believed to be cell‐autonomous in nature, including nonsecretory proteins, various classes of RNA, metabolites, and lipid membrane‐associated factors. Exosomes derived from mesenchymal stem/stromal cells (MSCs) appear to be particularly beneficial for enhancing recovery in various models of disease. To date, there have been more than 200 preclinical studies of exosome‐based therapies in a number of different animal models. Despite a growing number of studies reporting the therapeutic properties of MSC‐derived exosomes, their underlying mechanism of action, pharmacokinetics, and scalable manufacturing remain largely outstanding questions. Here, we review the global trends associated with preclinical development of MSC‐derived exosome‐based therapies, including immunogenicity, source of exosomes, isolation methods, biodistribution, and disease categories tested to date. Although the in vivo data assessing the therapeutic properties of MSC‐exosomes published to date are promising, several outstanding questions remain to be answered that warrant further preclinical investigation.

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<![CDATA[Are all stem cells equal? Systematic review, evidence map, and meta‐analyses of preclinical stem cell‐based therapies for bronchopulmonary dysplasia]]> https://www.researchpad.co/article/N3bfb6abd-a3e9-4397-aa68-8330a7045627

Abstract

Regenerative stem cell‐based therapies for bronchopulmonary dysplasia (BPD), the most common preterm birth complication, demonstrate promise in animals. Failure to objectively appraise available preclinical data and identify knowledge gaps could jeopardize clinical translation. We performed a systematic review and network meta‐analysis (NMA) of preclinical studies testing cell‐based therapies in experimental neonatal lung injury. Fifty‐three studies assessing 15 different cell‐based therapies were identified: 35 studied the effects of mesenchymal stromal cells (MSCs) almost exclusively in hyperoxic rodent models of BPD. Exploratory NMAs, for select outcomes, suggest that MSCs are the most effective therapy. Although a broad range of promising cell‐based therapies has been assessed, few head‐to‐head comparisons and unclear risk of bias exists. Successful clinical translation of cell‐based therapies demands robust preclinical experimental design with appropriately blinded, randomized, and statistically powered studies, based on biological plausibility for a given cell product, in standardized models and endpoints with transparent reporting.

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<![CDATA[Prenatal stem cell therapy for inherited diseases: Past, present, and future treatment strategies]]> https://www.researchpad.co/article/N4536bdc2-9326-4d8d-a03d-09b8764e7e0e

Abstract

Imagine the profits in quality of life that can be made by treating inherited diseases early in life, maybe even before birth! Immense cost savings can also be made by treating diseases promptly. Hence, prenatal stem cell therapy holds great promise for developing new and early‐stage treatment strategies for several diseases. Successful prenatal stem cell therapy would represent a major step forward in the management of patients with hematological, metabolic, or immunological disorders. However, treatment before birth has several limitations, including ethical issues. In this review, we summarize the past, the present, and the future of prenatal stem cell therapy, which includes an overview of different stem cell types, preclinical studies, and clinical attempts treating various diseases. We also discuss the current challenges and future strategies for prenatal stem cell therapy and also new approaches, which may lead to advancement in the management of patients with severe incurable diseases.

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