Cellular‐based therapies to prevent or reduce thrombocytopenia

Pineault, Nicolas; Boyer, Lucie

doi:10.1111/j.1537-2995.2011.03369.x

Cited by 11 publications

(10 citation statements)

References 62 publications

(124 reference statements)

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“…A majority of the studies presented in Table 5 have utilized protocols developed for the expansion of megakaryocyte-committed cells rather than HSCs (reviewed in [139]). However, only a handful of studies have assessed the impact of culture on the thrombopoietic activity of HSPC.…”

Section: Contribution Of Ex Vivo Expanded Progenitors To Short-term Hmentioning

confidence: 99%

Advances in umbilical cord blood stem cell expansion and clinical translation

Pineault

Abu‐Khader

2015

Experimental Hematology

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104

101

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Section: Contribution Of Ex Vivo Expanded Progenitors To Short-term Hmentioning

confidence: 99%

Advances in umbilical cord blood stem cell expansion and clinical translation

Pineault

Abu‐Khader

2015

Experimental Hematology

Self Cite

104

101

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“…The increased understanding of the biologic events that underlie human thrombopoiesis has been used by several groups to generate MK cell products that might be used to supplement or eventually replace donor‐derived PLT transfusions . Unfortunately, the utilization of such products for the treatment of thrombocytopenia has not advanced to the clinic beyond a limited number of safety/feasibility Phase I trials .…”

Section: Discussionmentioning

confidence: 99%

Pre‐clinical development of a cryopreservable megakaryocytic cell product capable of sustained platelet production in mice

et al. 2019

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BACKGROUND Platelet (PLT) transfusions are the most effective treatments for patients with thrombocytopenia. The growing demand for PLT transfusion products is compounded by a limited supply due to dependency on volunteer donors, a short shelf‐life, risk of contaminating pathogens, and alloimmunization. This study provides preclinical evidence that a third‐party, cryopreservable source of PLT‐generating cells has the potential to complement presently available PLT transfusion products. STUDY DESIGN AND METHODS CD34+ hematopoietic stem/progenitor cells derived from umbilical cord blood (UCB) units were used in a simple and efficient culture system to generate a cell product consisting of megakaryocytes (MKs) at different stages of development. The cultures thus generated were evaluated ex vivo and in vivo before and after cryopreservation. RESULTS We generated a megakaryocytic cell product that can be cryopreserved without altering its phenotypical and functional capabilities. The infusion of such a product, either fresh or cryopreserved, into immune‐deficient mice led to production of functional human PLTs which were observed within a week after infusion and persisted for 8 weeks, orders of magnitude longer than that observed after the infusion of traditional PLT transfusion products. The sustained human PLT engraftment was accompanied by a robust presence of human cells in the bone marrow (BM), spleen, and lungs of recipient mice. CONCLUSION This is a proof‐of‐principle study demonstrating the creation of a cryopreservable megakaryocytic cell product which releases functional PLTs in vivo. Clinical development of such a product is currently being pursued for the treatment of thrombocytopenia in patients with hematological malignancies.

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“…Hematopoietic stem cells (HSCs) are rare bone marrow (BM) resident multipotent cells with potential to self-renew and to replenish all nucleated [1] and anucleate blood cells [2], sustaining long-term multilineage reconstitution after physiological and clinical challenges including chemotherapy and bone marrow transplantations [3,4]. Allogeneic HSC transplantation remains the only curative treatment modality for numerous hematological malignancies, however inefficient blood lineage replenishment, especially neutropenia and thrombocytopenia remain a major cause of morbidity and mortality [5,6]. Single cell transplantation experiments have uncovered significant heterogeneity among reconstituting HSCs, which may reflect different propensities for lineage commitment by distinct myeloid-, lymphoid-and platelet-biased HSCs [2,[7][8][9][10].…”

Section: Main Textmentioning

confidence: 99%

Parallel clonal and molecular profiling of hematopoietic stem cells using RNA barcoding

Wójtowicz

Mistry

Uzun

et al. 2022

Preprint

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Anucleate cells - platelets and erythrocytes - constitute over 95% of all hematopoietic stem cell (HSC) output, but the clonal dynamics of HSC contribution to these lineages remains largely unexplored. Here, we use lentiviral RNA cellular barcoding and transplantation of HSCs, combined with single-cell RNA-seq, for quantitative analysis of clonal behavior with a multi-lineage readout - for the first time including anucleate and nucleate lineages. We demonstrate that most HSCs steadily contribute to hematopoiesis, but acute platelet depletion shifts the output of multipotent HSCs to the exclusive production of platelets, with the additional emergence of new myeloid-biased clones. Our approach therefore enables comprehensive profiling of multi-lineage output and transcriptional heterogeneity of individual HSCs, giving insight into clonal dynamics in both steady state and under physiological stress.

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Cellular‐based therapies to prevent or reduce thrombocytopenia

Cited by 11 publications

References 62 publications

Advances in umbilical cord blood stem cell expansion and clinical translation

Advances in umbilical cord blood stem cell expansion and clinical translation

Pre‐clinical development of a cryopreservable megakaryocytic cell product capable of sustained platelet production in mice

Parallel clonal and molecular profiling of hematopoietic stem cells using RNA barcoding

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