Progress in bio-manufacture of platelets for transfusion

Heazlewood, Shen Y.; Nilsson, Susan K.; Cartledge, Kellie; Be, Cheang Ly; Vinson, Andrew; Gel, Murat; Haylock, David N.

doi:10.1080/09537104.2016.1257783

Cited by 15 publications

(13 citation statements)

References 58 publications

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“…In fact, several studies reported enhanced PLT shedding in the presence of shear force, which mimics the blood stream, generated in a small flow chamber . More recently, the development of complex bioreactor systems, which reproduce not only the shear stresses but also the bone marrow perivascular space, showed higher PLT production efficiency reaching a yield of 100–150 PLTs/MK . Consequently, a combination of these innovative technologies with BC as source of HPCs may represent an enormous straight forward step towards in vitro PLT production for clinical use.…”

Section: Discussionmentioning

confidence: 99%

Blood donor‐derived buffy coat to produce platelets in vitro

et al. 2019

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Background and objectives Platelet transfusion is a standard medical therapy used to treat several bleeding disorders. However, a critical drawback is the dependency on donor-derived platelets, which leads to concerns like insufficient availability and immunological complications. In vitro platelet production from hematopoietic progenitor cells (CD34) may represent a reasonable solution.Materials and methods CD34+ cells were isolated from either buffy coat or peripheral blood and compared in terms of platelet production in vitro. The number and the quality of magnetically isolated CD34+ cells and their capability to differentiate into mature megakaryocytes were investigated using flow cytometry. Additionally, the functionality of megakaryocytes in term of in vitro platelet production was tested.Results Similar purity and quantity of CD34+ cells was found after their isolation from both cell sources. In contrast, after 6 days of culture, enhanced number of CD34+ cells isolated from buffy coat compared with peripheral blood was observed (5Á3 x 106 vs. 3Á0 x 106, respectively). Interestingly, despite a comparable nuclear maturation phenotype, the yield of platelets released from buffy coatderived megakaryocytes was significantly higher than from peripheral blood cells (platelet yield pro MK: 7Á2 vs. 2Á7, respectively). Importantly, platelets produced from buffy coat-derived cells could be activated by agonists.Conclusion Haematopoietic progenitor cells isolated from buffy coat have increased yield of platelets released from mature megakaryocytes and enhanced in vitro functionality, compared with peripheral blood-derived cells. Our study, suggests that buffy coat, obtained during blood donation processing, might be a promising source of megakaryocytes for in vitro platelet production.

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Section: Discussionmentioning

confidence: 99%

Blood donor‐derived buffy coat to produce platelets in vitro

et al. 2019

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“…Yields of PLT production may profit in the future from the harmonization of MK expansion and differentiation culture systems towards a synchronized PLT formation and release [74]. The application of shear stress in the designed bioreactor aimed to provide a physical cue to induce a synchronized proPLT formation, extension, and PLT release [80]. However, it remains highly desirable to identify biological or chemical signals that might support this process.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, imMKCLs, produced as discussed earlier in this review [49], from voluntary blood component donors with specific HLA haplotypes are currently being tested in a clinical phase I trial in Japan, initiated by Koji Eto [79]. The group demonstrated an approach for generation of 0.5 × 10 11 imMKCL-derived PLTs from each batch of an 8-liter culture [80]. The imMKCLs are analyzed for their PLT production capacity in vivo, determining their suitability in transfusion therapy.…”

Section: Clinical Applicationmentioning

confidence: 99%

Towards the Manufacture of Megakaryocytes and Platelets for Clinical Application

Baigger¹,

Blasczyk²,

Figueiredo³

2017

Transfus Med Hemother

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Platelet transfusions are used in standard clinical practice to prevent hemorrhage in patients suffering from thrombocytopenia or platelet dysfunctions. Recently, a constant rise on the demand of platelets for transfusion has been registered. This may be associated with several factors including demographic changes, population aging as well as incidence and prevalence of hematological diseases. In addition, platelet-regenerative properties have been started to be exploited in different areas such as tissue remodeling and anti-cancer therapies. These new applications are also expected to increase the future demand on platelets. Thus, in vitro generated platelets may constitute a highly desirable alternative to meet the rising demand on platelets. Several factors have been considered in the road trip of producing in vitro megakaryocytes and platelets for clinical application. From selection of the cell source, differentiation protocols and culture conditions to the design of optimal bioreactors, several strategies have been proposed to maximize production yields while preserving functionality. This review summarizes new advances in megakaryocyte and platelet differentiation and their production upscaling.

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“…Due to the limited availability of HSCs, further studies on iPSCs have been undertaken. Over the past years, iPSCs have shown great potential in biomedical research (38,39).…”

Section: Stem Cell Sourcesmentioning

confidence: 99%

Developments in the production of platelets from stem cells (Review)

et al. 2020

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Platelets are small pieces of cytoplasm that have become detached from the cytoplasm of mature megakaryocytes (MKs) in the bone marrow. Platelets modulate vascular system integrity and serve important role, particularly in hemostasis. With the rapid development of clinical medicine, the demand for platelet transfusion as a life-saving intervention increases continuously. Stem cell technology appears to be highly promising for transfusion medicine, and the generation of platelets from stem cells would be of great value in the clinical setting. Furthermore, several studies have been undertaken to investigate the potential of producing platelets from stem cells. Initial success has been achieved in terms of the yields and function of platelets generated from stem cells. However, the requirements of clinical practice remain unmet. The aim of the present review was to focus on several sources of stem cells and factors that induce MK differentiation. Updated information on current research into the genetic regulation of megakaryocytopoiesis and platelet generation was summarized. Additionally, advanced strategies of platelet generation were reviewed and the progress made in this field was discussed.

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Progress in bio-manufacture of platelets for transfusion

Cited by 15 publications

References 58 publications

Blood donor‐derived buffy coat to produce platelets in vitro

Blood donor‐derived buffy coat to produce platelets in vitro

Towards the Manufacture of Megakaryocytes and Platelets for Clinical Application

Developments in the production of platelets from stem cells (Review)

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