Strategies to enhance immunomodulatory properties and reduce heterogeneity in mesenchymal stromal cells during ex vivo expansion

Srinivasan, Akshaya; Sathiyanathan, Padmapriya; Yin, Lu; Liu, Tongming; Lam, Alan Tin-Lun; Ravikumar, Maanasa; Smith, Raymond A.; Loh, Han Ping; Zhang, Ying; Ling, Ling; Yang, Yuan Sheng; Lezhava, Alexander; Hui, James; Oh, Steve; Cool, Simon M.

doi:10.1016/j.jcyt.2021.11.009

Cited by 20 publications

(10 citation statements)

References 224 publications

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“…It has been suggested the preconditioning of MSCs may be necessary to generate potent anti-inflammatory properties for therapeutic use[ 68 , 69 ]. Techniques to augment the anti-inflammatory properties of MSCs include pre-culturing with pro-inflammatory cytokines in 3D culture conditions, preconditioning with chemical agents and/or through gene transfer approaches[ 70 , 71 ]. As none of the studies in our review reported augmenting the therapeutic properties of their MSCs using any of these techniques, this may explain the observed inability of MSCs to reduce pro-inflammatory cytokine levels and decrease mortality…”

Section: Discussionmentioning

confidence: 99%

Systematic review and meta-analysis of randomized controlled trials of mesenchymal stromal cells to treat coronavirus disease 2019: is it too late?

et al. 2023

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Section: Discussionmentioning

confidence: 99%

Systematic review and meta-analysis of randomized controlled trials of mesenchymal stromal cells to treat coronavirus disease 2019: is it too late?

et al. 2023

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“…Transcriptomic analyses have revealed that homozygous negative GSTT1 MSCs demonstrate increased scalability and potency, possibly due to increased protection from DNA damage [ 53 ]. Diagnostic kits to identify prospective donors are being developed, and may reduce unnecessary MSC harvesting from donors [ 132 ]. Other hypothesised genetic biomarkers, which may be validated in future studies, include the single-nucleotide polymorphism rs144383 in GDF5 , which is strongly associated with osteoarthritis [ 133 ].…”

Section: Managing the Heterogeneity Of Mscs For More Effective Cartil...mentioning

confidence: 99%

Managing the Heterogeneity of Mesenchymal Stem Cells for Cartilage Regenerative Therapy: A Review

et al. 2023

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Articular cartilage defects commonly result from trauma and are associated with significant morbidity. Since cartilage is an avascular, aneural, and alymphatic tissue with a poor intrinsic healing ability, the regeneration of functional hyaline cartilage remains a difficult clinical problem. Mesenchymal stem cells (MSCs) are multipotent cells with multilineage differentiation potential, including the ability to differentiate into chondrocytes. Due to their availability and ease of ex vivo expansion, clinicians are increasingly applying MSCs in the treatment of cartilage lesions. However, despite encouraging pre-clinical and clinical data, inconsistencies in MSC proliferative and chondrogenic potential depending on donor, tissue source, cell subset, culture conditions, and handling techniques remain a key barrier to widespread clinical application of MSC therapy in cartilage regeneration. In this review, we highlight the strategies to manage the heterogeneity of MSCs ex vivo for more effective cartilage repair, including reducing the MSC culture expansion period, and selecting MSCs with higher chondrogenic potential through specific genetic markers, surface markers, and biophysical attributes. The accomplishment of a less heterogeneous population of culture-expanded MSCs may improve the scalability, reproducibility, and standardisation of MSC therapy for clinical application in cartilage regeneration.

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“…Sorting of perinatal MSCs may be another effective approach for pre-selection, for example, pre-selection of MSC subpopulation using surface markers to increase the purity of the expanded MSCs. A series of markers need to be considered in sorting of perinatal MSCs, including cell surface markers related to MSC clonogenicity, potency, differentiation, and immunomodulatory properties[ 48 ]. Practically, a few conventional approaches to increasing the consistency of perinatal MSCs may be also considered, such as the use of the single colony of MSCs and specific biomaterials (see below), and the handing of MSCs by the standardized protocols for manufacturing consistency.…”

Section: Perinatal Msc Banking For Personalized Medicine Over Lifetim...mentioning

confidence: 99%

Banking of perinatal mesenchymal stem/stromal cells for stem cell-based personalized medicine over lifetime: Matters arising

Li¹,

Zhao²,

Zhang³

et al. 2023

World J Stem Cells

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Mesenchymal stromal/stem cells (MSCs) are currently applied in regenerative medicine and tissue engineering. Numerous clinical studies have indicated that MSCs from different tissue sources can provide therapeutic benefits for patients. MSCs derived from either human adult or perinatal tissues have their own unique advantages in their medical practices. Usually, clinical studies are conducted by using of cultured MSCs after thawing or short-term cryopreserved-then-thawed MSCs prior to administration for the treatment of a wide range of diseases and medical disorders. Currently, cryogenically banking perinatal MSCs for potential personalized medicine for later use in lifetime has raised growing interest in China as well as in many other countries. Meanwhile, this has led to questions regarding the availability, stability, consistency, multipotency, and therapeutic efficiency of the potential perinatal MSC-derived therapeutic products after long-term cryostorage. This opinion review does not minimize any therapeutic benefit of perinatal MSCs in many diseases after short-term cryopreservation. This article mainly describes what is known about banking perinatal MSCs in China and, importantly, it is to recognize the limitation and uncertainty of the perinatal MSCs stored in cryobanks for stem cell medical treatments in whole life. This article also provides several recommendations for banking of perinatal MSCs for potentially future personalized medicine, albeit it is impossible to anticipate whether the donor will benefit from banked MSCs during her/his lifetime.

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Strategies to enhance immunomodulatory properties and reduce heterogeneity in mesenchymal stromal cells during ex vivo expansion

Cited by 20 publications

References 224 publications

Systematic review and meta-analysis of randomized controlled trials of mesenchymal stromal cells to treat coronavirus disease 2019: is it too late?

Systematic review and meta-analysis of randomized controlled trials of mesenchymal stromal cells to treat coronavirus disease 2019: is it too late?

Managing the Heterogeneity of Mesenchymal Stem Cells for Cartilage Regenerative Therapy: A Review

Banking of perinatal mesenchymal stem/stromal cells for stem cell-based personalized medicine over lifetime: Matters arising

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