Development of platelet replacement therapy using human induced pluripotent stem cells

Nakamura, Sou; Sugimoto, Naoshi; Eto, Koji

doi:10.1111/dgd.12711

Cited by 5 publications

(2 citation statements)

References 86 publications

(113 reference statements)

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“…HSCs represent suitable starting material since as a natural process, they differentiate directly in megakaryocytes which then mature in platelets. Alternatives consist of the direct differentiation of induced pluripotent stem cells (iPSCs) into megakaryocytes or their progenitors ( Hansen et al, 2018 ; Shepherd et al, 2018 ; Nakamura et al, 2020 ) allowing the application of patient-derived cells and possible gene editing to address specific pathologies ( Bruschi et al, 2021 ; Nakamura et al, 2021 ).…”

Section: Platelet Generationmentioning

confidence: 99%

Functionalized 3D scaffolds for engineering the hematopoietic niche

Bruschi

Vanzolini

Sahu

et al. 2022

Front. Bioeng. Biotechnol.

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Hematopoietic stem cells (HSCs) reside in a subzone of the bone marrow (BM) defined as the hematopoietic niche where, via the interplay of differentiation and self-renewal, they can give rise to immune and blood cells. Artificial hematopoietic niches were firstly developed in 2D in vitro cultures but the limited expansion potential and stemness maintenance induced the optimization of these systems to avoid the total loss of the natural tissue complexity. The next steps were adopted by engineering different materials such as hydrogels, fibrous structures with natural or synthetic polymers, ceramics, etc. to produce a 3D substrate better resembling that of BM. Cytokines, soluble factors, adhesion molecules, extracellular matrix (ECM) components, and the secretome of other niche-resident cells play a fundamental role in controlling and regulating HSC commitment. To provide biochemical cues, co-cultures, and feeder-layers, as well as natural or synthetic molecules were utilized. This review gathers key elements employed for the functionalization of a 3D scaffold that demonstrated to promote HSC growth and differentiation ranging from 1) biophysical cues, i.e., material, topography, stiffness, oxygen tension, and fluid shear stress to 2) biochemical hints favored by the presence of ECM elements, feeder cell layers, and redox scavengers. Particular focus is given to the 3D systems to recreate megakaryocyte products, to be applied for blood cell production, whereas HSC clinical application in such 3D constructs was limited so far to BM diseases testing.

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Section: Platelet Generationmentioning

confidence: 99%

Functionalized 3D scaffolds for engineering the hematopoietic niche

Bruschi

Vanzolini

Sahu

et al. 2022

Front. Bioeng. Biotechnol.

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“… 19 The production of functional platelets from iPSC-derived megakaryocytes can be achieved but scaling up of this process to generate enough cells for therapy remains a significant challenge. 20 Cells of the monocyte/macrophage lineage can be produced at scale 21 but it is particularly interesting to note that these are considered to be more akin to myeloid cells generated in the embryo that go on to seed the resident populations within specific tissues rather than adult bone marrow derived cells. 22 This is in keeping with the widely accepted idea that PSC differentiation recapitulates embryonic, but not adult haematopoiesis.…”

Section: Cell Therapy For Haematopoietic Disorders and Deficienciesmentioning

confidence: 99%

Progress in the production of haematopoietic stem and progenitor cells from human pluripotent stem cells

Fidanza

Forrester

2021

Journal of Immunology and Regenerative Medicine

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Cell therapies are currently used to treat many haematological diseases. These treatments range from the long-term reconstitution of the entire haematopoietic system using the most potent haematopoietic stem cells (HSCs) to the short-term rescue with mature functional end cells such as oxygen-carrying red blood cells and cells of the immune system that can fight infection and repair tissue. Limitations in supply and the risk of transmitting infection has prompted the design of protocols to produce some of these cell types from human pluripotent stem cells (hPSCs). Although it has proven challenging to generate the most potent HSCs directly from hPSCs, significant progress has been made in the development of differentiation protocols that can successfully produce haematopoietic progenitor cells and most of the mature cell lineages. We review the key steps used in the production of haematopoietic stem and progenitor cells (HSPCs) from hPSCs and the cell surface markers and reporter strategies that have been used to define specific transitions. Most studies have relied on the use of known markers that define HSPC production in vivo but more recently single cell RNA sequencing has allowed a less biased approach to their characterisation. Transcriptional profiling has identified new markers for naïve and committed hPSC-derived HSPC populations and trajectory analyses has provided novel insights into their lineage potential. Direct comparison of in vitro- and in vivo -derived RNA single cell sequencing datasets has highlights similarities and differences between the two systems and this deeper understanding will be key to the design and the tracking of improved and more efficient differentiation protocols.

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