Current Stem Cell Reports最新文献_第6页

Preclinical Studies and Clinical Prospects of Wharton's Jelly-Derived MSC for Treatment of Acute Radiation Syndrome. 沃顿果冻源MSC治疗急性放射综合征的临床前研究和临床前景。

IF 1.4

Current Stem Cell Reports Pub Date : 2021-01-01 Epub Date: 2021-04-28 DOI: 10.1007/s40778-021-00188-4

Mayuri Bandekar, Dharmendra K Maurya, Deepak Sharma, Santosh K Sandur

{"title":"Preclinical Studies and Clinical Prospects of Wharton's Jelly-Derived MSC for Treatment of Acute Radiation Syndrome.","authors":"Mayuri Bandekar, Dharmendra K Maurya, Deepak Sharma, Santosh K Sandur","doi":"10.1007/s40778-021-00188-4","DOIUrl":"https://doi.org/10.1007/s40778-021-00188-4","url":null,"abstract":"Purpose of review: Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have received widespread attention from researchers owing to the remarkable benefits offered by these cells over other stem cells. The primitive nature of WJ-MSCs, ease of isolation, differentiation ability, and immuno-modulatory nature make these cells superior to bone marrow MSCs and ideal to treat various human ailments. This review explores ability of WJ-MSCs to mitigate acute radiation syndrome caused by planned or unplanned radiation exposure.Recent findings: Recent reports suggest that WJ-MSCs home to damaged tissues in irradiated host and mitigate radiation induced damage to radiosensitive tissues such as hematopoietic and gastrointestinal systems. WJ-MSCs and conditioned media were found to protect mice from radiation induced mortality and also prevent radiation dermatitis. Local irradiation-induced lung toxicity in mice was significantly reduced by CXCR4 over-expressing WJ-MSCs.Summary: Emerging evidences support safety and effectiveness of WJ-MSCs for treatment of acute radiation syndrome and lung injury after planned or accidental exposure. Additionally, conditioned media collected after culturing WJ-MSCs can also be used for mitigation of radiation dermatitis. Clinical translation of these findings would be possible after careful evaluation of resilience, effectiveness, and molecular mechanism of action of xenogeneic WJ-MSCs in non-human primates.","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-021-00188-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38940648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Regulatory Framework for Academic Investigator-Sponsored Investigational New Drug Development of Cell and Gene Therapies in the USA. 美国研究人员资助的细胞和基因疗法新药研究的监管框架。

IF 1.4

Current Stem Cell Reports Pub Date : 2021-01-01 Epub Date: 2021-09-30 DOI: 10.1007/s40778-021-00196-4

Anindya Dasgupta, Kristen Herzegh, H Trent Spencer, Christopher Doering, Eric Day, William P Swaney

{"title":"Regulatory Framework for Academic Investigator-Sponsored Investigational New Drug Development of Cell and Gene Therapies in the USA.","authors":"Anindya Dasgupta, Kristen Herzegh, H Trent Spencer, Christopher Doering, Eric Day, William P Swaney","doi":"10.1007/s40778-021-00196-4","DOIUrl":"https://doi.org/10.1007/s40778-021-00196-4","url":null,"abstract":"Purpose of review: The promise of cell and gene therapy (CGT) products for a multitude of diseases has revitalized investigators to advance novel CGT product candidates to first-in-human trials by pursuing the investigational new drug (IND) mechanism administered by the United States (US) Food and Drug Administration (FDA). This review is intended to familiarize academic investigators with the IND governing regulations set forth by the FDA.Recent findings: CGT products are extraordinarily complex biologics and, therefore, early-stage evaluation programs must be customized to satisfactorily address their unique developmental challenges. The US FDA continues to foster the development of transformational technology that will facilitate the broad application of safe and effective gene therapy products that have the potential to alleviate many conditions previously out of reach of therapeutic intervention. FDA is committed to working with the scientific community and industry to facilitate the availability of these treatments to patients.Summary: The pathway to meet regulatory compliance during early stage IND programs can be daunting to academic investigators interested in CGT product development that typically don't progress beyond phase 1/2. However, by keeping abreast of current regulatory framework and building upon FDA's supportive infrastructure, an investigator can be well-positioned to advance innovative scientific discoveries towards early stage clinical assessments.","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39509894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hematopoietic Stem Cell Stress and Regeneration 造血干细胞应激与再生

IF 1.4

Current Stem Cell Reports Pub Date : 2020-12-01 DOI: 10.1007/s40778-020-00181-3

C. Termini, J. Chute

引用次数: 2

The role of RNA epigenetic modification in normal and malignant hematopoiesis. RNA表观遗传修饰在正常和恶性造血中的作用。

IF 1.4

Current Stem Cell Reports Pub Date : 2020-12-01 Epub Date: 2020-08-12 DOI: 10.1007/s40778-020-00178-y

Radovan Vasic, Yimeng Gao, Chengyang Liu, Stephanie Halene

{"title":"The role of RNA epigenetic modification in normal and malignant hematopoiesis.","authors":"Radovan Vasic, Yimeng Gao, Chengyang Liu, Stephanie Halene","doi":"10.1007/s40778-020-00178-y","DOIUrl":"https://doi.org/10.1007/s40778-020-00178-y","url":null,"abstract":"Purpose of review: RNA epigenetic modifications have been identified as novel, dynamic regulators of gene expression, with important impacts on stem cell fate decisions. Here we examine the functions of RNA modifications, with a focus on N 6-methyladenosine (m6A), in hematopoietic stem cells under normal conditions and in malignancy.Recent findings: The m6A RNA modification is a critical regulator of hematopoiesis. Disruption of different elements of the m6A machinery can skew the balance of self-renewal and differentiation in normal hematopoietic stem cells. The m6A reader, writer, and eraser proteins are also overexpressed in myeloid leukemia, and disruption of their function impairs leukemogenesis. RNA m6A modification governs important aspects of immune system function, including immune cell development, immune signaling, and recognition of RNA as foreign or self. In hematopoietic stem cells, endogenously-derived double stranded RNA can form in the absence of m6A, inducing deleterious inflammatory pathways which compromise stem cell function.Summary: The RNA modification m6A exerts a variety of functions in normal hematopoietic stem cells as well as leukemic cells. Pharmacologic modulation of different elements of the m6A machinery provides a promising avenue for ex vivo expansion of hematopoietic stem cells in the transplant setting, as well as for leukemia therapy.","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-020-00178-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25525563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Stem Cell Metabolism and Diet. 干细胞代谢与饮食

IF 2.3

Current Stem Cell Reports Pub Date : 2020-12-01 Epub Date: 2020-10-28 DOI: 10.1007/s40778-020-00180-4

Marine Barthez, Zehan Song, Chih Ling Wang, Danica Chen

{"title":"Stem Cell Metabolism and Diet.","authors":"Marine Barthez, Zehan Song, Chih Ling Wang, Danica Chen","doi":"10.1007/s40778-020-00180-4","DOIUrl":"10.1007/s40778-020-00180-4","url":null,"abstract":"Purpose of review: Diet has profound impacts on health and longevity. Evidence is emerging to suggest that diet impinges upon the metabolic pathways in tissue-specific stem cells to influence health and disease. Here, we review the similarities and differences in the metabolism of stem cells from several tissues, and highlight the mitochondrial metabolic checkpoint in stem cell maintenance and aging. We discuss how diet engages the nutrient sensing metabolic pathways and impacts stem cell maintenance. Finally, we explore the therapeutic implications of dietary and metabolic regulation of stem cells.Recent findings: Stem Cell transition from quiescence to proliferation is associated with a metabolic switch from glycolysis to mitochondrial OXPHOS and the mitochondrial metabolic checkpoint is critically controlled by the nutrient sensors SIRT2, SIRT3, and SIRT7 in hematopoietic stem cells. Intestine stem cell homeostasis during aging and in response to diet is critically dependent on fatty acid metabolism and ketone bodies and is influenced by the niche mediated by the nutrient sensor mTOR.Summary: Nutrient sensing metabolic pathways critically regulate stem cell maintenance during aging and in response to diet. Elucidating the molecular mechanisms underlying dietary and metabolic regulation of stem cells provides novel insights for stem cell biology and may be targeted therapeutically to reverse stem cell aging and tissue degeneration.","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992378/pdf/nihms-1641673.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25525562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting the aryl hydrocarbon receptor in stem cells to improve the use of food as medicine. 靶向干细胞中芳烃受体，提高食品药用价值。

IF 1.4

Current Stem Cell Reports Pub Date : 2020-12-01 Epub Date: 2021-01-05 DOI: 10.1007/s40778-020-00184-0

Huajun Han, Arul Jayaraman, Stephen Safe, Robert S Chapkin

{"title":"Targeting the aryl hydrocarbon receptor in stem cells to improve the use of food as medicine.","authors":"Huajun Han, Arul Jayaraman, Stephen Safe, Robert S Chapkin","doi":"10.1007/s40778-020-00184-0","DOIUrl":"https://doi.org/10.1007/s40778-020-00184-0","url":null,"abstract":"Purpose of review: Intestinal stem cells, the most rapidly proliferating adult stem cells, are exquisitely sensitive to extrinsic dietary factors. Uncontrolled regulation of intestinal stem cells is closely linked to colon tumorigenesis. This review focuses on how dietary and microbial derived cues regulate intestinal stem cell functionality and colon tumorigenesis in mouse models by targeting the aryl hydrocarbon receptor (AhR).Recent findings: AhR, a ligand activated transcription factor, can integrate environmental, dietary and microbial cues to modulate intestinal stem cell proliferation, differentiation and their microenvironment, affecting colon cancer risk. Modulation of AhR activity is associated with many chronic diseases, including inflammatory bowel diseases where AhR expression is protective.Summary: AhR signaling controls the maintenance and differentiation of intestinal stem cells, influences local niche factors, and plays a protective role in colon tumorigenesis. Mounting evidence suggests that extrinsic nutritional/dietary cues which modulate AhR signaling may be a promising approach to colon cancer chemoprevention.","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-020-00184-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39313286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Use of MSCs and MSC-educated macrophages to mitigate hematopoietic acute radiation syndrome. 使用间充质干细胞和培养间充质干细胞的巨噬细胞减轻造血急性放射综合征。

IF 1.4

Current Stem Cell Reports Pub Date : 2020-09-01 Epub Date: 2020-08-08 DOI: 10.1007/s40778-020-00176-0

Raghavan Chinnadurai, Matthew H Forsberg, John A Kink, Peiman Hematti, Christian M Capitini

{"title":"Use of MSCs and MSC-educated macrophages to mitigate hematopoietic acute radiation syndrome.","authors":"Raghavan Chinnadurai, Matthew H Forsberg, John A Kink, Peiman Hematti, Christian M Capitini","doi":"10.1007/s40778-020-00176-0","DOIUrl":"https://doi.org/10.1007/s40778-020-00176-0","url":null,"abstract":"Purpose of review: Innovative and minimally toxic treatment approaches are sorely needed for the prevention and treatment of hematopoietic acute radiation syndrome (H-ARS). Cell therapies have been increasingly studied for their potential use as countermeasures for accidental and intentional ionizing radiation exposures which can lead to fatal ARS. Mesenchymal stem/stromal cells (MSCs) are a cell therapy that have shown promising results in preclinical studies of ARS, and are being developed in clinical trials specifically for H-ARS. MSCs, MSC-educated macrophages (MEMs) and MSC-exosome educated macrophages (EEMs) all have the potential to be used as adoptive cell therapies for H-ARS. Here we review how MSCs have been reported to mitigate inflammation from radiation injury while also stimulating hematopoiesis during ARS.Recent findings: We discuss emerging work with immune cell subsets educated by MSCs, including MEMs and EEMs, in promoting hematopoiesis in xenogeneic models of ARS. We also discuss the first placental-derived MSC product to enter phase I trials, PLX-R18, and the challenges faced by bringing MSC and other cell therapies into the clinic for treating ARS.Summary: Although MSCs, MEMs and EEMs are potential cell therapy candidates in promoting hematopoietic HRS, challenges persist in translational clinical development of these products to the clinic. Whether any of these cellular therapies will be sufficient as stand-alone therapies to mitigate H-ARS or if they will be a bridging therapy that insures survival until a curative allogeneic hematopoietic stem cell transplant can be performed are the key questions that will have to be answered.","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-020-00176-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38392151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Mechanoregulation in hematopoiesis and hematologic disorders. 造血和血液学疾病的机械调节。

IF 1.4

Current Stem Cell Reports Pub Date : 2020-09-01 Epub Date: 2020-05-21 DOI: 10.1007/s40778-020-00172-4

Paulina D Horton, Sandeep Dumbali, Pamela L Wenzel

{"title":"Mechanoregulation in hematopoiesis and hematologic disorders.","authors":"Paulina D Horton, Sandeep Dumbali, Pamela L Wenzel","doi":"10.1007/s40778-020-00172-4","DOIUrl":"10.1007/s40778-020-00172-4","url":null,"abstract":"Purpose of review: Hematopoietic stem cells (HSCs) are reliant on intrinsic and extrinsic factors for tight control of self-renewal, quiescence, differentiation, and homing. Given the intimate relationship between HSCs and their niche, increasing numbers of studies are examining how biophysical cues in the hematopoietic microenvironment impact HSC functions.Recent findings: Numerous mechanosensors are present on hematopoietic cells, including integrins, mechanosensitive ion channels, and primary cilia. Integrin-ligand adhesion, in particular, has been found to be critical for homing and anchoring of HSCs and progenitors in the bone marrow. Integrin-mediated interactions with ligands present on extracellular matrix and endothelial cells are key to establishing long-term engraftment and quiescence of HSCs. Importantly, disruption in the architecture and cellular composition of the bone marrow associated with conditioning regimens and primary myelofibrosis exposes HSCs to a profoundly distinct mechanical environment, with potential implications for progression of hematologic dysfunction and pathologies.Summary: Study of the mechanobiological signals that govern hematopoiesis represents an important future step toward understanding HSC biology in homeostasis, aging, and cancer.","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-020-00172-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38520533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Genome Editing for Rare Diseases. 罕见疾病的基因组编辑。

IF 2.3

Current Stem Cell Reports Pub Date : 2020-09-01 Epub Date: 2020-07-07 DOI: 10.1007/s40778-020-00175-1

Arun Pradhan, Tanya V Kalin, Vladimir V Kalinichenko

{"title":"Genome Editing for Rare Diseases.","authors":"Arun Pradhan, Tanya V Kalin, Vladimir V Kalinichenko","doi":"10.1007/s40778-020-00175-1","DOIUrl":"10.1007/s40778-020-00175-1","url":null,"abstract":"Purpose of the review: Significant numbers of patients worldwide are affected by various rare diseases, but the effective treatment options to these individuals are limited. Rare diseases remain underfunded compared to more common diseases, leading to significant delays in research progress and ultimately, to finding an effective cure. Here, we review the use of genome-editing tools to understand the pathogenesis of rare diseases and develop additional therapeutic approaches with a high degree of precision.Recent findings: Several genome-editing approaches, including CRISPR/Cas9, TALEN and ZFN, have been used to generate animal models of rare diseases, understand the disease pathogenesis, correct pathogenic mutations in patient-derived somatic cells and iPSCs, and develop new therapies for rare diseases. The CRISPR/Cas9 system stands out as the most extensively used method for genome editing due to its relative simplicity and superior efficiency compared to TALEN and ZFN. CRISPR/Cas9 is emerging as a feasible gene-editing option to treat rare monogenic and other genetically defined human diseases.Summary: Less than 5% of ~7000 known rare diseases have FDA-approved therapies, providing a compelling need for additional research and clinical trials to identify efficient treatment options for patients with rare diseases. Development of efficient genome-editing tools capable to correct or replace dysfunctional genes will lead to novel therapeutic approaches in these diseases.","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653884/pdf/nihms-1610082.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38600412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hematopoietic Stem Cells in Health and Disease—Insights from Single-Cell Multi-omic Approaches 造血干细胞在健康和疾病中的作用——来自单细胞多组学方法的见解

IF 1.4

Current Stem Cell Reports Pub Date : 2020-07-06 DOI: 10.1007/s40778-020-00174-2

S. Haas

引用次数: 6