Microfluidic label-free bioprocessing of human reticulocytes from erythroid culture

Zeming, Kerwin Kwek; Satô, Yukô; Yin, Lu; Huang, Nai Jia; Wong, Lawson L. S.; Loo, Hooi Linn; Lim, Ying Bena; Lim, Chwee Teck; Chen, Jianzhu; Preiser, Peter R.; Han, Jongyoon

doi:10.1039/c9lc01128e

Cited by 20 publications

(16 citation statements)

References 56 publications

(80 reference statements)

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“…In 2020, Guzniczak et al demonstrated a two-stage separation process consisting first of a microfluidic chamber that employs deformability-based RBC sorting followed by a membrane filtration step for an overall cell purity of 99% in the final product [ 179 ]. In the same year, Zeming and colleagues investigated both Dean Flow Filtration (DFF) and Deterministic Lateral Displacement (DLD) sorting using a microfluidic approach and demonstrated that both methods were capable of achieving higher cell recovery over traditional fluorescence cell sorting [ 180 ]. Studies such as these are vital towards the development of clinically relevant bioprocesses, not just for blood production, but for many other systems with cellular products.…”

Section: Generating Clinically Suitable Ipsc-rbcs For Transfusionmentioning

confidence: 99%

Industrially Compatible Transfusable iPSC-Derived RBCs: Progress, Challenges and Prospective Solutions

Lim

Vassilev

Leong

et al. 2021

IJMS

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Amidst the global shortfalls in blood supply, storage limitations of donor blood and the availability of potential blood substitutes for transfusion applications, society has pivoted towards in vitro generation of red blood cells (RBCs) as a means to solve these issues. Many conventional research studies over the past few decades have found success in differentiating hematopoietic stem and progenitor cells (HSPCs) from cord blood, adult bone marrow and peripheral blood sources. More recently, techniques that involve immortalization of erythroblast sources have also gained traction in tackling this problem. However, the RBCs generated from human induced pluripotent stem cells (hiPSCs) still remain as the most favorable solution due to many of its added advantages. In this review, we focus on the breakthroughs for high-density cultures of hiPSC-derived RBCs, and highlight the major challenges and prospective solutions throughout the whole process of erythropoiesis for hiPSC-derived RBCs. Furthermore, we elaborate on the recent advances and techniques used to achieve cost-effective, high-density cultures of GMP-compliant RBCs, and on their relevant novel applications after downstream processing and purification.

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Section: Generating Clinically Suitable Ipsc-rbcs For Transfusionmentioning

confidence: 99%

Industrially Compatible Transfusable iPSC-Derived RBCs: Progress, Challenges and Prospective Solutions

Lim

Vassilev

Leong

et al. 2021

IJMS

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“…More experimental approaches include lab-on-a-chip microfluidic label-free reticulocyte-sorting methods. 66 All these possibilities need testing and optimizing on a large culture scale which is expensive, therefore, highlighting filtration as a key area of research calling for innovation as well as commercial investment and collaboration.…”

Section: Reticulocyte Filtration and Storagementioning

confidence: 99%

Towards manufactured red blood cells for the treatment of inherited anemia

2021

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Patients with inherited anemia and hemoglobinopathies (such as sickle cell disease and β-thalassemia) are treated with red blood cell (RBC) transfusions to alleviate their symptoms. Some of these patients may have rare blood group types or go on to develop alloimmune reactions, which can make it difficult to source compatible blood in the donor population. Laboratory-grown RBC represent a particularly attractive alternative which could satisfy an unmet clinical need. The challenge, however, is to produce - from a limited number of stem cells - the 2x1012 RBC required for a standard adult therapeutic dose. Encouraging progress has been made in RBC production from adult stem cells under good manufacturing practice. In 2011, the Douay group conducted a successful proof-of-principle mini-transfusion of autologous manufactured RBC in a single volunteer. In the UK, a trial is planned to assess whether manufactured RBC are equivalent to RBC produced naturally in donors, by testing an allogeneic mini-dose of laboratory-grown manufactured RBC in multiple volunteers. This review discusses recent progress in the erythroid culture field as well as opportunities for further scaling up of manufactured RBC production for transfusion practice.

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“…They found that the positions of the streamlines were in good agreement with the experimental results and were able to use the computer model to aid in their microfluidic chip design. Research has also been carried out on other methods of cell separation, such as separation by cell rigidity [53]. Regarding studies on malaria, there are, again, only a few examples that were implemented in COMSOL.…”

Section: Simulationsmentioning

confidence: 99%

“…There is a wide range of methods for simulating microfluidics using a variety of software. One of the more popular and used software is COMSOL Multiphysics version 5.5 (COMSOL, Boston, MA, USA) with the microfluidics add-on module [52][53][54][55].…”

Section: Simulationsmentioning

confidence: 99%

Systematic Review: Microfluidics and Plasmodium

et al. 2021

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Malaria affects 228 million people worldwide each year, causing severe disease and worsening the conditions of already vulnerable populations. In this review, we explore how malaria has been detected in the past and how it can be detected in the future. Our primary focus is on finding new directions for low-cost diagnostic methods that unspecialized personnel can apply in situ. Through this review, we show that microfluidic devices can help pre-concentrate samples of blood infected with malaria to facilitate the diagnosis. Importantly, these devices can be made cheaply and be readily deployed in remote locations.

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Microfluidic label-free bioprocessing of human reticulocytes from erythroid culture

Abstract: Developments in Dean flow fractionation (DFF) and deterministic lateral displacement (DLD) for label-free purification of cultured RBCs from human hematopoietic stem cells. An advancement in sorting and closed-loop manufacturing of viable human RBCs.

Cited by 20 publications

References 56 publications

Industrially Compatible Transfusable iPSC-Derived RBCs: Progress, Challenges and Prospective Solutions

Industrially Compatible Transfusable iPSC-Derived RBCs: Progress, Challenges and Prospective Solutions

Towards manufactured red blood cells for the treatment of inherited anemia

Systematic Review: Microfluidics and Plasmodium

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