Umbilical cord blood graft engineering: challenges and opportunities

Thompson, Philip A.; Rezvani, Katy; Hosing, Chitra; Oran, Betül; Olson, Amanda; Popat, Uday; Alousi, Amin M.; Shah, Nina; Parmar, Simrit; Bollard, Catherine M.; Hanley, Patrick J.; Kebriaei, Partow; Cooper, Laurence J.N.; Kellner, Joshua; McNiece, Ian; Shpall, Elizabeth J.

doi:10.1038/bmt.2015.97

Cited by 28 publications

(21 citation statements)

References 135 publications

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“…Extensive investigation of strategies to enhance myeloid engraftment is underway 113,114 . Expansion methods that are currently in clinical trials include ex vivo expansion of stem/progenitor cells utilizing culture in the presence of Notch ligand 115 , a mesenchymal co-culture system 116 , and culture with the addition of small molecules (nicotinamide 117 , StemRegenin-1 118 and UM171 119 ).…”

Section: New Technologiesmentioning

confidence: 99%

“…Enhanced homing is an alternative approach and fucosylation is currently under investigation 124 . In addition to enhancing myeloid recovery, strategies to prevent and treat viral infections in CBT recipients through the provision of cytotoxic T-cells are also under development 114,125 . The infusion of third-party CB-derived T-regulatory cells is being investigated as novel GVHD prophylaxis 126 , and third-party EBV-specific cytotoxic T lymphocytes can be effective therapy for EBV-PTLD 127 .…”

Section: New Technologiesmentioning

confidence: 99%

See 1 more Smart Citation

Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies

Barker

Kurtzberg

Ballen

et al. 2017

Biology of Blood and Marrow Transplantation

119

115

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Unrelated donor cord blood (CB) transplantation (CBT) results in disease-free survival comparable to that of unrelated adult donor transplantation in patients with hematologic malignancies. Extension of allograft access to racial and ethnic minorities, rapid graft availability, flexibility of transplant date, and low risks of disabling chronic graft-versus-host disease (GVHD) and relapse are significant advantages of CBT, and multiple series have reported a low risk of late transplant-related mortality (TRM) post-transplant. Nonetheless, early post-transplant morbidity and TRM and the requirement for intensive early post-transplant management have slowed wide adoption of CBT. Targeted care strategies in CBT recipients can, however, mitigate early transplant complications and reduce transplant costs. Herein, we provide a practical “how to” guide to CBT for hematologic malignancies on behalf of the NMDP and the ASBMT CB Special Interest Group (SIG). It shares the best practices of 6 experienced United States transplant centers with a special interest in the use of CB as a hematopoietic stem cell source. We address donor search and unit selection, unit thaw and infusion, conditioning regimens, immune suppression, management of GVHD, opportunistic infections and other factors in supportive care appropriate for CBT. Meticulous attention to such details has improved CBT outcomes and will facilitate the success of CBT as a platform for future graft manipulations.

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Section: New Technologiesmentioning

confidence: 99%

Section: New Technologiesmentioning

confidence: 99%

Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies

Barker

Kurtzberg

Ballen

et al. 2017

Biology of Blood and Marrow Transplantation

119

115

View full text Add to dashboard Cite

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“…24 and reviewed in ref. 25), and we have begun testing nuclease-mediated genetic modification of blood cells in this system.…”

Section: Discussionmentioning

confidence: 99%

Semi-automated closed system manufacturing of lentivirus gene-modified haematopoietic stem cells for gene therapy

Adair¹,

Waters²,

Haworth³

et al. 2016

Nat Commun

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Haematopoietic stem cell (HSC) gene therapy has demonstrated potential to treat many diseases. However, current state of the art requires sophisticated ex vivo gene transfer in a dedicated Good Manufacturing Practices facility, limiting availability. An automated process would improve the availability and standardized manufacture of HSC gene therapy. Here, we develop a novel program for semi-automated cell isolation and culture equipment to permit complete benchtop generation of gene-modified CD34+ blood cell products for transplantation. These cell products meet current manufacturing quality standards for both mobilized leukapheresis and bone marrow, and reconstitute human haematopoiesis in immunocompromised mice. Importantly, nonhuman primate autologous gene-modified CD34+ cell products are capable of stable, polyclonal multilineage reconstitution with follow-up of more than 1 year. These data demonstrate proof of concept for point-of-care delivery of HSC gene therapy. Given the many target diseases for gene therapy, there is enormous potential for this approach to treat patients on a global scale.

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“…Stage 1 had identified—as expected—that stem cell graft sources are associated with immune reconstitution kinetics (e.g. cord on average slower compared with PBSC 27 ), and we therefore stratified our patients by graft source in stage 2. The model of stage 2 now included microbial genera as additional predictors of observed changes in white blood cell counts to the medications selected in stage 1, clinical features (conditioning intensity, age, sex), and the current state of the blood in the form of counts of neutrophils, lymphocytes, monocytes, eosinophils, and platelets.…”

Section: Main Textmentioning

confidence: 99%

An association between the gut microbiota and immune cell dynamics in humans

Schluter

et al. 2019

Preprint

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22The gut microbiota influences the development and homeostasis of the mammalian immune system 1-23 3 , can alter immune cell compositions in mice [4][5][6][7] , and is associated with responses to immunotherapy 24 that rely on the activity of peripheral immune cells [8][9][10][11][12] . Still, our understanding of how the microbiota 25 modulates circulatory immune cells remains limited, particularly in humans where a lack of 26 manipulative experiments makes inference challenging. Here we overcome this challenge by studying 27 hundreds of hospitalized-and closely monitored-bone marrow transplantation patients as they 28 recover from chemotherapy-induced immune ablation. This aggressive treatment causes large shifts in 29 both circulatory immune cell and microbiota populations, allowing the relationships between the two 30 to be studied simultaneously over time with unprecedented resolution. We analyzed daily changes in 31 white blood cell counts from 2,235 patients, and 10,680 longitudinal fecal microbiota samples to 32 identify bacterial genera consistently associated with those changes. Bayesian inference and 33 validation across different patient cohorts revealed consistent associations between intestinal bacteria 34 and peripheral immune cell dynamics in the context of immunomodulatory medications, clinical 35 metadata and homeostatic feedbacks between peripheral immune cells. The quantification of validated 36 microbiota associations enabled us to contrast the potency of fermentatively active, obligate anaerobic 37 bacteria with that of medications with known immunomodulatory mechanism, and this way estimate 38 the microbiota potential to alter peripheral immune cell dynamics directly in patients. Our analysis 39 establishes and quantifies the link between the intestinal microbiota and immune cell dynamics in 40 humans, with implications for microbiota-driven modulation of immunity and immunotherapies that 41 rely on circulatory immune cells. 42 3 MAIN TEXT 43

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Umbilical cord blood graft engineering: challenges and opportunities

Cited by 28 publications

References 135 publications

Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies

Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies

Semi-automated closed system manufacturing of lentivirus gene-modified haematopoietic stem cells for gene therapy

An association between the gut microbiota and immune cell dynamics in humans

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