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Improved manufacturing of bone marrow-derived mesenchymal stromal cells for cartilage repair
Purpose
Improved manufacturing of bone marrow-derived mesenchymal stromal cells for cartilage repair
Crosscut Captains
Despite increasing clinical application of mesenchymal stromal cells (MSCs) in cartilage regeneration, the outcomes have been plagued by substantial variability and inconsistency. A large contributor to such unpredictable outcomes stemmed from the heterogeneity nature of MSC. The heterogeneity stem first from the inherent donor-to-donor variation in MSC functionality, that is influenced by the genetic, age and health conditions of the donor. During laboratory propagation to generate sufficient cell quantity for therapeutic application, processing and protocol differences further perpetuate cell heterogeneity, critically affecting the functional quality of the expanded cells. There is, therefore, an urgent need to develop functional critical quality attributes (CQAs) to predict MSC chondrogenic efficacy, and enrichment approaches to improve the consistency of MSC delivered to the patients.
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
Harnessing Self-Renewing Cells for Treatment of Cartilage Damage
Asia-Pacific Biotech News, Vol 26, Nos. 11 & 12, November & December 2022
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
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
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
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
2024
SMART CAMP Authors
Zheng Yang (NUS/SMART) , Yingnan Wu (NUS), Shu Hui Neo (SMART), Dahou Yang (SMART), Hyungkook Jeon (MIT), Ching Ann Tee (SMART), Vinitha Denslin (NUS), Daryl Jimian Lin (NUS) , Eng Hin Lee (NUS), Laurie A Boyer (MIT/SMART), Jongyoon Han (MIT/SMART)
Size-Based Microfluidic-Enriched Mesenchymal Stem Cell Subpopulations Enhance Articular Cartilage Repair
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
2023
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
2022
SMART CAMP Authors
Conference Presentations
Shruthi Pandi Chelvam, Alice Ng Jie Ying, Huang Jiayi, Elizabeth Lee, Derrick Yong, Rajeev Ram, Stacy Springs, Rohan B.H. Williams
SMART CAMP Authors
2023
Ching Ann Tee, Daniel Ninio Roxby, Antony Dhasan Josphin Denslin, Lisa Tucker-Kellogg, Laurie A. Boyer
SMART CAMP Authors
2023
Ching Ann Tee, Daniel Ninio Roxby, Antony Dhasan Josphin Denslin, Lisa Tucker-Kellogg, Laurie A. Boyer
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
SMART CAMP Authors
2022
Yanmeng Yang (SMART), Yingnan Wu (NUS), Jian Xiong Tan (NUS), Eng Hin Lee (NUS), Zheng Yang (NUS)
SMART CAMP Authors
2022
Bottleneck 1
MSCs can be potent therapies for cartilage repair but efficacy is unpredictable due to donor-donor variation and heterogeneity that develops in culture.
Bottleneck 2
Lack of predictable MSC target product profile for cartilage repair efficacy.
Goal 1
To develop automated, high-throughput, and label-free cell sorters for the isolation of MSC subpopulations with superior chondrogenic potential in vitro and in vivo.
Goal 2
To identify key scalable, label-free CQAs and development of cognate process analytical tools (PATs) to monitor production of MSC-based therapies that are correlative to function, using lower amounts of cells and/or consumables.
