Ziya Isiksacan, PhD, holds the position of research fellow at the Center for Engineering in Medicine and Surgery (CEMS). Serving as the lead author, she collaborated with various international institutes and disciplines on a significant study titled "Assessment of Stored Red Blood Cells Through Lab-on-a-Chip Technologies for Precision Transfusion Medicine." The senior author of the research is Osman Berk Usta, PhD, who is an investigator at CEMS, Massachusetts General Hospital, and also an associate professor of Surgery at Harvard Medical School.

Published in the esteemed journal PNAS, this groundbreaking article aims to spark discussions and drive positive change in the realm of stored blood assessment. The study seeks to improve the methods used for evaluating stored blood, with the ultimate goal of advancing precision transfusion medicine.

What Question Were You Investigating?

This perspective article addresses the pressing issues surrounding the quality of stored Red Blood Cells (RBCs) and the lack of adequate assessment before transfusion. The authors, along with others in the field, propose that the current practices regarding stored RBCs may not always guarantee safe transfusions due to various factors such as donor variability, time in storage, and processing methods. This poses a particular risk for critically ill patients, individuals on chronic transfusion regimens, and surgeries where substantial volumes of RBCs are required.

The article highlights a significant gap in personalized medicine: the absence of quantitative assessment of stored RBCs on an individual unit basis. To address this concern, the authors anticipate that advanced technologies such as -omics and machine learning will play a pivotal role over the next decade. By leveraging these cutting-edge tools, the authors envision the identification of key quantitative quality metrics (referred to as a "quality index") for stored RBCs. These quality indices could then serve as a basis for lab-on-a-chip platforms equipped with innovative biosensors. Through continuous monitoring, these platforms can assess the quality of stored RBCs and match the specific properties of each unit to the unique needs of the patient, thus advancing precision transfusion medicine.

What Were Your Findings?

The uniqueness of this article lies in its extensive and diverse authorship, representing a wide range of stakeholders crucial to implementing the proposed solutions discussed in the perspective. The authors come from various fields, including hematology, transfusion medicine, blood storage and biopreservation, -omics, engineering, life sciences, global health, and ethics. This inclusive approach ensures a comprehensive perspective as experts from both academic and industrial backgrounds contribute their insights and viewpoints. By incorporating such a diverse set of experts, the article aims to present well-rounded and holistic solutions that address the multifaceted challenges surrounding the subject matter.

Lab-on-a-chip technologies have the potential to revolutionize the transfusion workflow, offering an objective assessment of stored RBC units through the use of quality metrics identified by -omics and machine learning. This advancement heralds a new era in precision transfusion medicine. By addressing both the possibilities and challenges of this approach, we can envision a future where each stored RBC unit undergoes evaluation before transfusion, guided by a comprehensive quality index.

To realize this transformative vision, active involvement from all stakeholders is essential. Experts in blood banking, biopreservation, transfusion medicine, -omics, machine learning, bioengineering, ethics, regulation, and most importantly, patients, must come together in multidisciplinary discussions and collaborations. This Perspective article, featuring a diverse team of such stakeholders, represents a significant step towards achieving the envisioned era of precision in transfusion medicine. By moving away from isolated efforts and fostering a convergent approach, we can enhance the safety and efficacy of transfusions, ultimately benefiting patients and advancing the field as a whole.

What Are the Clinical Implications?

In this perspective, we present our envisioned workflow designed to enhance the safety and efficacy of transfusion, ultimately resulting in fewer adverse effects and complications. As emphasized, the absence of quality assessment for stored RBCs poses significant challenges, particularly for critically ill patients, those on chronic transfusion regimens, and surgeries involving substantial RBC transfusions. Therefore, the successful implementation of our envisioned workflows would mark a momentous advancement in patient safety.

By ensuring objective quality assessment of stored RBC units through the application of cutting-edge technologies, such as lab-on-a-chip platforms and -omics analysis, we aim to mitigate potential risks associated with transfusions. The comprehensive evaluation of each RBC unit before transfusion, guided by a quality index, will offer greater assurance of their suitability for specific patients' needs. This transformation has the potential to yield safer and more effective transfusion practices, significantly benefiting patients across various medical scenarios.

What Are the Next Steps?

A consortium of authors, representing diverse stakeholders, collaborated on this perspective to envision and forge a safer future for transfusion medicine through the integration of advanced technologies. The shared goal is to enhance safety and efficiency in transfusions, thereby benefiting patients and medical practices alike.

As a follow-up to this perspective, the next crucial steps involve establishing interactive forums, including conferences and workgroups. These platforms will serve as channels to engage and mobilize a broader community of stakeholders. By fostering open discussions and collaborations, the envisioned goals outlined in this perspective can be translated into concrete actions. Through these dynamic interactions, the consortium aims to catalyze the implementation of innovative solutions in transfusion medicine, ultimately elevating the standards of patient care and safety.

The consortium of authors includes: Dr. Ziya Isiksacan (microfluidics, biopreservation, RBC morphology, electrical engineering - MGH & Shriners Children’s), Dr. Angelo D’Alessandro (Metabolomics, proteomics, biochemistry, transfusion medicine, RBC biology – U. Colorado Anschutz), Dr. Susan M. Wolf (bioethics, law,  health law, science law – U. Minnesota), Dr. David H. McKenna ( transfusion medicine, blood, cell therapy, quality control, pathology – U. Minnesota), Dr. Shannon N. Tessier (biopreservation, biochemistry, MGH & Shriners Children’s), Dr. Erdem Kucukal (RBC disorders, hemorheology, commercialization mechanical engineering – Biochips Labs), Dr. Aslihan A. Gokaltun (biopreservation, biomaterials, polymer science, chemical engineering - MGH & Shriners Children’s), Nishaka William (biopreservation, RBC biology – U. Alberta), Dr. Rebecca D. Sandlin (Cryobiology, biostabilization, global health – MGH & Shriners Children’s), Dr. John Bischof (biopreservation, nanowarming, cryobiology, mechanical engineering), Dr. Narla Mohandas (Hematology, transfusion medicine, blood banking, RBC biology – New York Blood Center), Dr. Michael P. Busch (transfusion medicine and safety, blood safety, infectious diseases – Vitalant Research Institute & U. California San Francisco), Dr. Caglar Elbuken (Microfluidics, point-of-care diagnostics, instrumentation, RBC morphology, biosensors – U. Oolu & Bilkent U)., Dr. Umut A. Gurkan (RBC disorders, clinical microfluidics, point-of-care diagnostics, commercialization, mechanical engineering – Case Western U. & Biochips Labs), Dr. Mehmet Toner (microfluidics, point-of-care diagnostics, biopreservation, global health, mechanical engineering  - MGH & Shriners Children’s) , Dr. Jason P. Acker (cryobiology, RBC biology, oxidative injury, transfusion medicine, blood banking, U. Alberta & Canadian Blood Services), Dr. Martin L. Yarmush (biopreservation, tissue engineering, biochemistry, microfluidics, biomedical engineering - MGH & Shriners Children’s), Dr. O. Berk Usta (biopreservation, microfluidics, tissue engineering, biomedical engineering) – MGH & Shriners Children’s).

Paper Cited:

Isiksacan Z, D’Alessandro A, Wolf SM, McKenna DH, Tessier SN, Kucukal E, Gokaltun AA, William N, Sandlin RD, Bischof J, Mohandas N, Busch MP, Elbuken C, Gurkan UA, Toner M, Acker JP, Yarmush ML, Usta OB (2023). Assessment of stored red blood cells through lab-on-a-chip-technologies for precision transfusion medicinePNAS 10.1073/pnas.2115616120

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.

Journal Link: PNAS

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