Flagship Project 1

Efficacy CQA

Label-free critical quality attributes for personalized efficacy of cell therapies, including multivariate analysis of biological and biophysical attributes

What ?

Label-free critical quality attributes for personalized efficacy of cell therapies, including multivariate analysis of biological and biophysical attributes.

Why ?

For regulatory approval and clinical use, cell therapies must be demonstrated as both safe and effective. While this expectation of manufacturing standards seems obvious based on Phase I-IV clinical trials for a range of pharmaceutical products and medical devices, for most emerging and approved cell therapies it still remains challenging to relate therapeutic efficacy (in the animal or human patient) to the properties of the cells themselves.

What we do ?

FP1 addresses and identifies CQAs that (i) correlate with therapeutic efficacy and that (ii) are amenable to intermittent or inline monitoring of the therapeutic dose because the CQA measurement does not label, tag, or detectably alter the cells’ therapeutic efficacy. While these CQAs will be specific to a given cell type/source and its intended target indication (disease or injury repair), the general framework of cell population measurement (even at single cell resolution), multivariate data analytics, and validated correlation among biological, biophysical, and therapeutic outcome data is shared. Thus, FP1 will develop and demonstrate this CQA approach for multiple distinct cell types that provide contrast in technical requirements and synergies in CQA validation methodology development, including relatively surface-adherent cells such as mesenchymal stromal/stem cells and relatively non-adherent cells such as T cells.

Highlights

SMART discovers novel method to predict effectiveness of mesenchymal stromal cells (MSCs) for cartilage repair

SMART researchers have developed a new method to assess the potential of mesenchymal stromal cells (MSCs) to repair cartilage. This method is faster (9 days) compared to the current standard (21 days) and uses a simpler 2D culture system The new method analyses specific fingerprint-like patterns or topological defects in MSCs to predict how effective they will be for cartilage repair therapy This new method is non-destructive and also more accurate than existing ones, allowing researchers to identify effective cell batches and enable the development of new and more efficient cartilage regeneration therapies

Publications

Meiqi Kang (SMART), Yanmeng Yang (SMART), Haifeng Zhang (NUS), Yuan Zhang (NUS), Yingnan Wu (NUS), Vinitha Denslin (NUS), Rashidah Binte Othman (SMART), Zheng Yang (NUS/SMART) and Jongyoon Han (MIT/SMART)

Comparative Analysis of Serum and Serum-Free Medium Cultured Mesenchymal Stromal Cells for Cartilage Repair

International J. of Molecular Sciences, 2024, 25, 10627. ; Oct 02, 2024
2024

SMART CAMP Authors

Ching Ann Tee (SMART), Daniel Ninio Roxby (SMART), Rashidah Othman (SMART), Vinitha Denslin (NUS), Kiseer Sideeq Bhat (SMART), Zheng Yang (NUS), Jongyoon Han (MIT/SMART), Lisa Tucker-Kellogg (Duke-NUS) & Laurie A. Boyer (MIT/SMART)

Metabolic modulation to improve MSC expansion and therapeutic potential for articular cartilage repair

Stem Cell Research & Therapy, Volume 15, Article number: 308 ; Sep 16, 2024
2024

SMART CAMP Authors

Brandon Krupczak (MIT), Camille Farruggio (MIT) and Krystyn J. Van Vliet (MIT/SMART)

Manufacturing mesenchymal stromal cells in a microcarrier-microbioreactor platform can enhance cell yield and quality attributes: case study for acute respiratory distress syndrome

Journal of Translational Medicine (2024) 22:614; Jul 02, 2024
2024

SMART CAMP Authors

Ekta Makhija (SMART), Yang Zheng (NUS), Jiahao Wang (NUS), Han Ren Leong (NUS), Rashidah Binte Othman (SMART), Ee Xien Ng (SMART), Eng Hin Lee (NUS), Lisa Tucker Kellogg (Duke-NUS), Yie Hou Lee (SMART), Hanry Yu (NUS), Zhiyong Poon (SGH), Krystyn J. Van Vliet (MIT/SMART)

Topological defects in self-assembled patterns of mesenchymal stromal cells in vitro are predictive attributes of condensation and chondrogenesis

PLOS ONE, 19(3): e0297769.; Mar 28, 2024
2024

SMART CAMP Authors

Ching Ann Tee (SMART), Jongyoon Han (MIT/SMART), Hoi Po James Hui (NUS), Eng Hin Lee (NUS/SMART), and Zheng Yang (NUS/SMART)

Perspective in achieving stratified articular cartilage repair using zonal chondrocytes

Tissue Engineering Part B: Reviews., 29 (3), pp. 310-330; Jun 07, 2023
2023

SMART CAMP Authors

Smitha Surendran Thamarath (SMART), Ching Ann Tee (SMART), Shu Hui Neo (SMART), Dahou Yang (SMART), Rashidah Othman (SMART), Laurie A Boyer (MIT/SMART), Jongyoon Han (MIT/SMART)

Rapid and Live-Cell Detection of Senescence in Mesenchymal Stem Cells by Micro Magnetic Resonance Relaxometry

Stem Cells Translational Medicine, 12 (5), pp. 266–280,; May 01, 2023
2023

SMART CAMP Authors

Khloe S. Gordon, Taeyoon Kyung, Caleb R. Perez, Patrick V. Holec, Azucena Ramos, Angela Q. Zhang, Yash Agarwal, Yunpeng Liu, Catherine E. Koch, Alina Starchenko, Brian A. Joughin, Douglas A. Lauffenburger, Darrell J. Irvine, Michael T. Hemann & Michael E. Birnbaum

Screening for CD19-specific chimaeric antigen receptors with enhanced signalling via a barcoded library of intracellular domains`

Nature Biomedical Engineering, 6, pp. 855–866; Jun 16, 2022
2022

SMART CAMP Authors

Ching Ann Tee, Zheng Yang, Yingnan Wu, Xiafei Ren, Maciej Baranski, Daryl Jimian Lin, Afizah Hassan, Jongyoon Han, Eng Hin Lee

A Pre-Clinical Animal Study for Zonal Articular Cartilage Regeneration Using Stratified Implantation of Microcarrier Expanded Zonal Chondrocytes

Cartilage, April-June 2022, pp. 1-16; Apr 21, 2022
2022

SMART CAMP Authors

Chayakorn Petchakupa, Paul Edward Hutchinson, Hui Min Tay, Sheng Yuan Leong, King Ho Holden Li, Han Wei Hou

Label-free quantitative lymphocyte activation profiling using microfluidic impedance cytometry

Sensors and Actuators B: Chemical, 339, 129864; Jul 15, 2021
2021

SMART CAMP Authors

Kerwin Kwek Zeming, Rohan Vernekar, Mui Teng Chua, Kai Yun Quek, Greg Sutton, Timm Krüger, Win Sen Kuan, Jongyoon Han

Label‐Free Biophysical Markers from Whole Blood Microfluidic Immune Profiling Reveal Severe Immune Response Signatures

Small, 17 (12), 2006123; Mar 25, 2021
2021

SMART CAMP Authors

Lingyan Gong, Chayakorn Petchakup, Pujiang Shi, Pei Leng Tan, Lay Poh Tan, Chor Yong Tay, and Han Wei Hou

Direct and Label-Free Cell Status Monitoring of Spheroids and Microcarriers Using Microfluidic Impedance Cytometry

Small, 17 (21), 2007500; Mar 24, 2021
2021

SMART CAMP Authors

Kerwin Kwek Zeming, Ri Lu, Kai Lee Woo, Guoyun Sun, Kai Yun Quek, Lih Feng Cheow, Chia-Hung Chen, Jongyoon Han, and Shir Lynn Lim

Multiplexed Single-Cell Leukocyte Enzymatic Secretion Profiling from Whole Blood Reveals Patient-Specific Immune Signature

Analytical Chemistry, 93 (10), pp. 4374–4382; Feb 18, 2021
2021

SMART CAMP Authors

Ng Ee Xien, Wang Ming, Neo Shu Hui, Tee Ching Ann, Chen Chia-Hung, Van Vliet Krystyn

Dissolvable gelatin-based microcarriers generated through droplet microfluidics for expansion and culture of mesenchymal stromal cells

Biotechnology Journal, 16 (3), 2000048; Oct 13, 2020
2020

SMART CAMP Authors

Guoyun Sun, Yao Teng, Zixuan Zhao, Lih Feng Cheow, Hanry Yu, and Chia-Hung Chen

Functional Stem Cell Sorting via Integrative Droplet Synchronization

Analytical Chemistry, 92 (11), 7915–7923; May 07, 2020
2020

SMART CAMP Authors

Lu Yin, Zheng Yang, Yingnan Wu, Vinitha Denslin, Chia Chen Yu, Ching Ann Tee, Chwee Teck Lim, Jongyoon Han, Eng Hin Lee

Label-free separation of mesenchymal stem cell subpopulations with distinct differentiation potencies and paracrine effects

Biomaterials, 40, 119881; May 01, 2020
2020

SMART CAMP Authors

Conference Presentations

Ching Ann Tee, Daniel Ninio Roxby, Antony Dhasan Josphin Denslin, Lisa Tucker-Kellogg, Laurie A. Boyer

"Metabolic modulation in MSC manufacturing to improve MSC therapeutic potential for articular cartilage repair", Singapore Cell & Gene Therapy Conference 2023, Aug 04, 2023-Aug 05, 2023, Singapore

SMART CAMP Authors

2023

Ekta Makhija (SMART), Yang Zheng (NUS), Jiahao Wang (MBI), Han Ren Leong (NUS), Rashidah Binte Othman (SMART), Ee Xien Ng (SMART), Eng Hin Lee (NUS), Lisa Tucker-Kellogg (Duke-NUS), Yie Hou Lee (SMART), Hanry Yu (NUS), Zhiyong Poon (SGH), Krystyn J. Van Vliet (MIT

"Emergent patterns in mesenchymal stromal cell monolayer predict efficacy of cartilage formation", 14th Stem Cell Society Singapore Symposium 2022, Dec 07, 2022-Dec 09, 2022, Singapore

SMART CAMP Authors

2022

Nicholas Tan (SMART), Kerwin Kwek (SMART), Quek Kai Yun (SMART), Teo Kim Leng (A*STAR BTI), Loberas Mavis Gayle Lumawag (NUS), Steve Oh (A*STAR BTI), Hou Han Wei (NTU) Jongyoon Han (MIT)

"Mesenchymal stem cell enrichment augmented through microfluidics from bone marrow aspirate", 14th Stem Cell Society Singapore Symposium 2022, Dec 07, 2022-Dec 09, 2022, Singapore

SMART CAMP Authors

2022

Wei-Xiang SIN (SMART), Denise TEO (SMART), Kevin S. LEE (Erbi Biosystems Inc), Harry LEE (Erbi Biosystems Inc), Narendra Suhas JAGANNATHAN (Duke-NUS), Rajeev RAM (MIT), Lisa TUCKER-KELLOGG (Duke-NUS), Michael BIRNBAUM (MIT)

"High Density CAR T Cell Culture with a 2-mL Continuous Perfusion Bioreactor", 14th Stem Cell Society Singapore Symposium 2022, Dec 07, 2022-Dec 09, 2022, Singapore

SMART CAMP Authors

2022

Yanmeng Yang (SMART), Yingnan Wu (NUS), Jian Xiong Tan (NUS), Eng Hin Lee (NUS), Zheng Yang (NUS)

"Secretome derived from hypoxia preconditioned mesenchymal stem cells promote cartilage regeneration and mitigate joint inflammation via extracellular vesicles", 14th Stem Cell Society Singapore Symposium 2022, Dec 07, 2022-Dec 09, 2022, Singapore

SMART CAMP Authors

2022

Zheng Yang (NUS), Dahou Yang (SMART), Yingnan Wu (NUS), Vinitha Denslin (NUS), Jaylen Tan (SMART), Eng Hin Lee (NUS), Jongyoon Han (MIT)

"Multi-dimensional double spiral microfluidic selection of MSC subpopulation with more efficacious chondrogenic potential", 14th Stem Cell Society Singapore Symposium 2022, Dec 07, 2022-Dec 09, 2022, Singapore

SMART CAMP Authors

2022

Wei-Xiang SIN (SMART), Faye CHEUNG (SMART), Sandy LEE (A*STAR SIgN), Dedy SANDIKIN (SMART), Denise TEO (SMART), Faris KAIRI (SMART), Cheng-I WANG (A*STAR SIgN), Michael BIRNBAUM (MIT)

"Characterization of LVV-Transduced, In Vitro-Expanded Anti-TIM3 CAR T Cells", 14th Stem Cell Society Singapore Symposium 2022, Dec 07, 2022-Dec 09, 2022, Singapore

SMART CAMP Authors

2022

Kevin S. Lee (Erbi Biosystems Inc.), Wei-Xiang Sin (SMART), Michael Birnbaum (MIT)

"Cell therapy process development with a 2 mL continuous perfusion bioreactor", 27th ESACT Meeting, Jun 26, 2022-Jun 29, 2022, Lisbon, Portugal

SMART CAMP Authors

2022

Wei-Xiang Sin (SMART), Kevin S. Lee (Erbi Biosystems Inc.), Harry Lee (Erbi Biosystems Inc.), Michael Birnbaum (MIT)

"High density CAR T cell culture with a 2 mL continuous perfusion bioreactor", SDCT-REMEDIS Cell Therapy Conference, Jun 23, 2022-Jun 24, 2022, Virtual (Singapore)

SMART CAMP Authors

2022

Wei-Xiang Sin

"Cell therapy process development with a 2 mL continuous perfusion bioreactor", A*STAR Advances in Cell and Gene Therapy (A*CGT) Symposium, May 11, 2022-Jun 12, 2022, Singapore

SMART CAMP Authors

2022

Zhi Xian Chan, Linxin Hou, Elizabeth Lee, Ching Ann Tee, and Derrick Yong

"Feature Analysis on Label-Free Multimodal Images of Mesenchymal Stromal Cells with Different Metabolic States", Microscopy Histopathology and Analytics 2022, Apr 24, 2022-Apr 27, 2022, Fort Lauderdale, Florida United States

SMART CAMP Authors

2022

Kevin S. Lee (Erbi Biosystems Inc, Wei-Xiang Sin (SMART), Harry Lee (Erbi Biosystems Inc.), Michael Birnbaum (MIT)

"Erbi Biosystems - Cell culture development with a 2 mL continuous perfusion bioreactor", Advancing Manufacture of Cell and Gene Therapies VII, Engineering Conference International, Feb 06, 2022-Feb 10, 2022, Coronado, CA, USA

SMART CAMP Authors

2022

N. Persits (MIT), C.C. Farruggio (MIT), Rajeev Ram (MIT), and K. Van Vliet (MIT)

"Metabolite Monitoring of Mesenchymal Stromal Cell Cultures by Spontaneous Raman Spectroscopy", Annual meeting of the American Institute of Chemical Engineers (AIChe), Nov 07, 2021-Nov 19, 2021, Virtual

SMART CAMP Authors

2021

Elizabeth Lee (SMART), Maciej Baranski (SMART), Marvin Chew (SMART), Wei Xiang Sin (SMART), Ka-Wai Cheung (SMART), Lisa Tucker-Kellogg (Duke-NUS), Derrick Yong (A*STAR-SIMTech), Michael Birnbaum (MIT), and George Barbastathis (MIT)

"Supervised Dimensionality Reduction of Single-cell Features from Label-free Multimodal Images for T Cell Subtype Classification", Frontiers in Optics/Laser Science 2021, Nov 01, 2021-Nov 04, 2021, Virtual, Washington, DC United States

SMART CAMP Authors

2021

Yong, Zixin (SMART), Elizabeth Lee (SMART), Maciej Baranski (SMART), Lisa Tucker-Kellogg (Duke-NUS), and George Barbastathis (MIT)

"CycleGAN for Reflection and Aberration Artifact Removal in Quantitative Phase Images of Mesenchymal Stromal Cells", Novel Techniques in Microscopy, Optical Society of America, April 2021., Apr 12, 2021-Apr 16, 2021, Virtual

SMART CAMP Authors

2021

Lee, Elizabeth (SMART), Maciej Baranski (SMART), Zixin Yong (SMART), Lakshmi Venkatraman (SMART), Derrick Yong (A*STAR-SIMTech), and George Barbastathis (MIT)

"Multimodal Microscopy for Label-free Monitoring of Mesenchymal Stromal Cells", Frontiers in Optics 2020, Optical Society of America, Sep 14, 2020-Sep 17, 2020, Virtual, Washington, DC, United States

SMART CAMP Authors

2020