Characterization of immune-matched hematopoietic transplantation in zebrafish
Jill L. O. de JongCaroline E. BurnsAye T. ChenEmily K. PugachElizabeth A. MayhallAlexandra SmithHenry A. FeldmanYi ZhouLeonard I. Zon
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Hematopoietic stem cells (HSCs) save lives in routine clinical practice every day, as they are the key element in transplantation-based therapies for hematologic malignancies. The success of clinical stem cell transplantation critically relies on the ability of stem cells to reconstitute the hematopoietic system for many decades after the administration of the powerful chemotherapy and/or irradiation that is required to eradicate malignant cells, but also irreversibly ablates patients’ own blood forming capacity. Surprisingly, despite enormous efforts and continuous progress in the field, our understanding of the basic biology of HSCs is still rather incomplete. Several recent studies substantially refine our understanding of the cells at the very top of the hematopoietic hierarchy, and suggest that we may need to revise the criteria we typically use to identify and define HSCs.
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Objective To give a summary of the current researches on hematopoietic stem cell niche.Methods Through extensive reviewing the related domestic and abroad literatures,the present summary reviews the compo- nents of hematopoietic stem cell niche,related cell factors and related cell signaling pathway participating in regula- tion of hematopoietic stem cell.Results The activities of hematopoietic stem cells are regulated by the niche(micro- environment),which is composed of hematopoietic stem cell and its surrounding cells.The regulation cannot be completed through one signaling pathway.Also,the self-renewal and differentiation of hematopoietic stem cell can- not be completed only through osteoblastic cells.Conclusion The niche regulates hematopoietic stem cells by differ- ent ways.With study in-depth,we will comprehensively understand the nature of stem cells and the study will pro- vide a broader space to stem cell-based therapy.
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Part I. Biological Basis of Hematopoietic Stem Cell Transplantation Part II. Methods and Procedures in Hematopoietic Stem Cell Transplantation Part III. Clinical Results I Part IV. Clinical Results II Part V. Clinical Results III Part VI. Family Member Mismatched Hematopoietic Stem Cell Transplantation Part VII. Unrelated Donor Hematopoietic Stem Cell Transplantation Part VIII. Umbilical Cord Blood Transplantation Part IX. Major Transplant-Related Complications Part X. Organ-Specific Complications Part XI. Laboratory Services Part XII. Statistical Analysis Part XIII. Developing Areas in Hematopoietic Stem Cell Transplantation Part XIV. The Future.
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Hematopoietic stem cell (HSC) transplantation is the most prevalent stem cell therapy, but it remains a risky procedure. To improve this treatment, it is important to understand how transplanted stem cells rebuild the blood and immune systems and how this process is impacted by transplantation variables such as the HSC dose. Here, we find that, in the long term following transplantation, 70%-80% of donor-HSC-derived clones do not produce all measured blood cell types. High HSC doses lead to more clones that exhibit balanced lymphocyte production, whereas low doses produce more T-cell-specialized clones. High HSC doses also produce significantly higher proportions of early-differentiating clones compared to low doses. These complex differentiation behaviors uncover the clonal-level regeneration dynamics of hematopoietic regeneration and suggest that transplantation dose can be exploited to improve stem cell therapy.
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The marrow repopulating hematopoietic stem cells (HSCs) in an auto- or allograft represent a small fraction of the normal complement of HSCs, yet are required to reconstitute hematopoiesis and sustain it for the lifetime of the recipient. Such a burden imposes a “replicative stress” upon hematopoietic stem/progenitor cells. The finding of accelerated telomere shortening in hematopoietic stem cell transplant (HSCT) recipients raised the specter of accelerated hematopoietic aging. Here, we review the HSCT telomere literature and other studies of surrogate markers of HSC behavior conducted in human HSCT recipients. We present a paradigm for posttransplant hematopoietic reconstitution and speculate on the fate of HSCs in the human transplant setting.
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Hematopoietic stem cells are the cells primarily responsible for short term and long term hematological reconstitution when a graft is infused into a myeloablated host. The number and quality of hematopoietic stem cells within a graft are the major determinants of the time to and durability of hematological reconstitution of a transplant recipient. Ex vivo hematopoietic stem cell expansion is, therefore, a critical component of several potentially important clinical strategies including gene therapy, tumor purging and graft engineering. Recent clinical trials using a variety of ex vivo hematopoietic stem cells expansion systems have, to date, met with limited success. Recognition of the consequences of hematopoietic stem cell self-replication will assist in the development of new approaches to hematopoietic stem cell expansion. The use of suitable in vivo models to assay the marrow repopulating potential of expanded hematopoietic stem cell products is a vital step prior to entry again into clinical trials.
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