Scalable mesenchymal stem cell enrichment from bone marrow aspirate using deterministic lateral displacement (DLD) microfluidic sorting.

Autor: Tan Kwan Zen N; Critical Analytics for Manufacturing of Personalized Medicine, Singapore-MIT Alliance for Research and Technology (SMART), 138602, Singapore.; School of Mechanical and Aerospace Engineering, Nanyang Technological University, 639798, Singapore., Zeming KK; Critical Analytics for Manufacturing of Personalized Medicine, Singapore-MIT Alliance for Research and Technology (SMART), 138602, Singapore., Teo KL; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 138668, Singapore., Loberas M; NUS Tissue Engineering Program, Life Sciences Institute, National University of Singapore, 117510, Singapore.; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 119288, Singapore., Lee J; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 138668, Singapore., Goh CR; Critical Analytics for Manufacturing of Personalized Medicine, Singapore-MIT Alliance for Research and Technology (SMART), 138602, Singapore., Yang DH; Critical Analytics for Manufacturing of Personalized Medicine, Singapore-MIT Alliance for Research and Technology (SMART), 138602, Singapore., Oh S; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 138668, Singapore., Hui Hoi Po J; NUS Tissue Engineering Program, Life Sciences Institute, National University of Singapore, 117510, Singapore.; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 119288, Singapore., Cool SM; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 119288, Singapore.; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 138668, Singapore.; School of Chemical Engineering, University of Queensland, Brisbane, 4072, Australia., Hou HW; Critical Analytics for Manufacturing of Personalized Medicine, Singapore-MIT Alliance for Research and Technology (SMART), 138602, Singapore.; School of Mechanical and Aerospace Engineering, Nanyang Technological University, 639798, Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore., Han J; Critical Analytics for Manufacturing of Personalized Medicine, Singapore-MIT Alliance for Research and Technology (SMART), 138602, Singapore.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA.; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA. jyhan@mit.edu.
Jazyk: angličtina
Zdroj: Lab on a chip [Lab Chip] 2023 Sep 26; Vol. 23 (19), pp. 4313-4323. Date of Electronic Publication: 2023 Sep 26.
DOI: 10.1039/d3lc00379e
Abstrakt: The growing interest in regenerative medicine has opened new avenues for novel cell therapies using stem cells. Bone marrow aspirate (BMA) is an important source of stromal mesenchymal stem cells (MSCs). Conventional MSC harvesting from BMA relies on archaic centrifugation methods, often leading to poor yield due to osmotic stress, high centrifugation force, convoluted workflow, and long experimental time (∼2-3 hours). To address these issues, we have developed a scalable microfluidic technology based on deterministic lateral displacement (DLD) for MSC isolation. This passive, label-free cell sorting method capitalizes on the morphological differences between MSCs and blood cells (platelets and RBCs) for effective separation using an inverted L-shaped pillar array. To improve throughput, we developed a novel multi-chip DLD system that can process 2.5 mL of raw BMA in 20 ± 5 minutes, achieving a 2-fold increase in MSC recovery compared to centrifugation methods. Taken together, we envision that the developed DLD platform will enable fast and efficient isolation of MSCs from BMA for effective downstream cell therapy in clinical settings.
Databáze: MEDLINE
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